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51. Association of menopausal characteristics and risk of coronary heart disease: A pan-European case-cohort analysis

Author: Dam, V. Van Der Schouw, Y.T. Onland-Moret, N.C. Groenwold, R.H.H. Peters, S.A.E. Burgess, S. Wood, A.M. Chirlaque, M.-D. Moons, K.G.M. Oliver-Williams, C. Schuit, E. Tikk, K. Weiderpass, E. Holm, M. Tjønneland, A. Kühn, T. Fortner, R.T. Trichopoulou, A. Karakatsani, A. La Vecchia, C. Ferrari, P. Gunter, M. Masala, G. Sieri, S. Tumino, R. Panico, S. Boer, J.M.A. Monique Verschuren, W.M. Salamanca-Fernández, E. Arriola, L. Moreno-Iribas, C. Engström, G. Melander, O. Nordendahl, M. Wennberg, P. Key, T.J. Colorado-Yohar, S. Matullo, G. Overvad, K. Clavel-Chapelon, F. Boeing, H. Ramon Quiros, J. Di Angelantonio, E. Langenberg, C. Sweeting, M.J. Riboli, E. Wareham, N.J. Danesh, J. Butterworth, A.
Abstract: Background: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. Methods: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. Results: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors. Conclusions: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovascular risk factors and disease. © 2019 The Author(s).
Published: 2019

52. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author: Harris, S.E., Corley, J., Wojczynski, M.K., Nauck, M., Levy, D., Gu, C., Sorensen, T.I.A., Noordam, R., Guo, X., Hill, W.D., Chen, Y.-D.I., Liu, C., Yao, J., Kraja, A.T., Daw, E.W., Irvin, M.R., Christensen, C., Newman, A.B., Hansen, T., Hudson, G., Zeng, D., Wu, H., Uitterlinden, A.G., Wareham, N.J., Perls, T.T., Grarup, N., Broeckel, U., Luan, J., Fu, M., Hemani, G., de Mutsert, R., Lin, S.J., Wilson, J.G., Jorgensen, M.E., Witte, D.R., Have, C.T., Ribel-Madsen, R., Wang, Y., Love-Gregory, L.D., Bowden, D.W., Province, M.A., Rotter, J.I., Taylor, A.M., Hunt, S.C., Thyagarajan, B., Goodarzi, M.O., Ridker, P.M., Torp-Pedersen, C., Ligthart, S., Starr, J.M., Feitosa, M.F., Arnett, D.K., de Haan, H.G., Jorgensen, T., Weeke, P.E., Graff, M., de las Fuentes, L., Justice, A.E., Hayward, C., Kerrison, N.D., Pedersen, O., Bonnelykke, K., Perry, J.A., Fetterman, J.L., Hai, Y., Malik, A.N., Vestergaard, H., Cropp, C.D., Ryan, K.A., Christensen, K., The Population Sciences Branch, NHLBI/NIH, Armasu, S.M., Langenberg, C., Forouhi, N.G., Yang, W., Teumer, A., Rodriguez, S., Kardia, S.L.R., Qi, Q., Becker, D.M., Baranski, T.J., Yanek, L.R., Rao, D.C., Fernandez, E.P., Lin, K.-H., Li-Gao, R., Sofer, T., Nohr, E.A., Larson, N.B., Sheu, W.H.-H., Elliott, P., An, P., Schnurr, T.M., Gu, Z., Taylor, K.D., Davies, G., Kilpelainen, T.O., Lee, W.-J., Patki, A., Barve, R.A., Brandslund, I., Sandow, K., Weiss, S., Wang, L., Stergiakouli, E., Mathias, R.A., Ghanbari, M., Tiwari, H.K., Rivadeneira, F., Davila-Roman, V.G., de Andrade, M., North, K.E., Richardson, T.G., Horta, B.L., Bielinski, S.J., Linneberg, A., Young, K., Argos, M., Dehghan, A., Chasman, D.I., Mook-Kanamori, D.O., Vaidya, D., Petersmann, A., Scott, R.A., Meigs, J.B., Ahluwalia, T.S., Gao, H., Rosendaal, F.R., Chakravarti, A., van Heemst, D., Cox, S.R., Williams, C., Pankow, J., Giulianini, F., Weir, B.S., Jonsson, A.E., Hartwig, F.P., Rohde, R., Ikram, M.A., Homuth, G., Lee, J.H., Deary, I.J., Erzurumluoglu, A.M., Chu, A.Y., Emery, L.S., Franco, O.H., Ong, K.K., Arking, D.E., Loos, R.J.F., Tzoulaki, I., Pattie, A., Timpson, N.J., and Turner, S.T.
Abstract: Mitochondria (MT), the major site of cellular energy production, are under dual genetic control by 37 mitochondrial DNA (mtDNA) genes and numerous nuclear genes (MT-nDNA). In the CHARGEmtDNA+ Consortium, we studied genetic associations of mtDNA and MT-nDNA associations with body mass index (BMI), waist-hip-ratio (WHR), glucose, insulin, HOMA-B, HOMA-IR, and HbA1c. This 45-cohort collaboration comprised 70,775 (insulin) to 170,202 (BMI) pan-ancestry individuals. Validation and imputation of mtDNA variants was followed by single-variant and gene-based association testing. We report two significant common variants, one in MT-ATP6 associated (p ≤ 5E−04) with WHR and one in the D-loop with glucose. Five rare variants in MT-ATP6, MT-ND5, and MT-ND6 associated with BMI, WHR, or insulin. Gene-based meta-analysis identified MT-ND3 associated with BMI (p ≤ 1E−03). We considered 2,282 MT-nDNA candidate gene associations compiled from online summary results for our traits (20 unique studies with 31 dataset consortia's genome-wide associations [GWASs]). Of these, 109 genes associated (p ≤ 1E−06) with at least 1 of our 7 traits. We assessed regulatory features of variants in the 109 genes, cis- and trans-gene expression regulation, and performed enrichment and protein-protein interactions analyses. Of the identified mtDNA and MT-nDNA genes, 79 associated with adipose measures, 49 with glucose/insulin, 13 with risk for type 2 diabetes, and 18 with cardiovascular disease, indicating for pleiotropic effects with health implications. Additionally, 21 genes related to cholesterol, suggesting additional important roles for the genes identified. Our results suggest that mtDNA and MT-nDNA genes and variants reported make important contributions to glucose and insulin metabolism, adipocyte regulation, diabetes, and cardiovascular disease.
Published: 2019
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53. Dietary antioxidants and asthma in adults

Author: Patel, B.D., Welch, A.A., Bingham, S.A., Luben, R.N., Day, N.E., Khaw, K.-T., Lomas, D.A., and Wareham, N.J.
Subjects: Asthma -- Development and progression, Asthma -- Risk factors, Antioxidants -- Health aspects, Antioxidants -- Research, Health
Published: 2006

54. Moderate weight change following diabetes diagnosis and 10 year incidence of cardiovascular disease and mortality.

Author: Wareham N.J., Long G.H., Hare M.J.L., Irving G., Boothby C.E., Griffin S.J., Strelitz J., Ahern A.L., Wareham N.J., Long G.H., Hare M.J.L., Irving G., Boothby C.E., Griffin S.J., Strelitz J., and Ahern A.L.
Abstract: Aims/hypothesis: Adults with type 2 diabetes are at high risk of developing cardiovascular disease (CVD). Evidence of the impact of weight loss on incidence of CVD events among adults with diabetes is sparse and conflicting. We assessed weight change in the year following diabetes diagnosis and estimated associations with 10 year incidence of CVD events and all-cause mortality. Method(s): In a cohort analysis among 725 adults with screen-detected diabetes enrolled in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Cambridge trial, we estimated HRs for weight change in the year following diabetes diagnosis and 10 year incidence of CVD (n = 99) and all-cause mortality (n = 95) using Cox proportional hazards regression. We used linear regression to estimate associations between weight loss and CVD risk factors. Models were adjusted for age, sex, baseline BMI, smoking, occupational socioeconomic status, cardio-protective medication use and treatment group. Result(s): Loss of >=5% body weight in the year following diabetes diagnosis was associated with improvements in HbA1c and blood lipids and a lower hazard of CVD at 10 years compared with maintaining weight (HR 0.52 [95% CI 0.32, 0.86]). The associations between weight gain vs weight maintenance and CVD (HR 0.41 [95% CI 0.15, 1.11]) and mortality (HR 1.63 [95% CI 0.83, 3.19]) were less clear. Conclusions/interpretation: Among adults with screen-detected diabetes, loss of >=5% body weight during the year after diagnosis was associated with a lower hazard of CVD events compared with maintaining weight. These results support the hypothesis that moderate weight loss may yield substantial long-term CVD reduction, and may be an achievable target outside of specialist-led behavioural treatment programmes.Copyright © 2019, The Author(s).
Published: 2019

55. Associations of autozygosity with a broad range of human phenotypes

Author: Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. (Murielle), Boehnke, M. (Michael), Bouchard, C. (Claude), Bradfield, J.P. (Jonathan), Brody, J.A. (Jennifer A), Campbell, A. (Archie), Carmi, S. (Shai), Caulfield, M. (Mark), Cesarini, D. (David), Chambers, J.C. (John C), Chandak, G.R. (Giriraj), Cheng, C.-Y. (Ching-Yu), Ciullo, M. (Marina), Warrington, N.M. (Nicole), Cusi, D. (Daniele), Smith, G.D. (George Davey), Deary, I.J. (Ian J), Dorajoo, R. (Rajkumar), Duijn, C.M. (Cornelia) van, Ellinghaus, D. (David), Erdmann, J. (Jeanette), Hagen, K. (Knut), Evangelou, E. (Evangelos), Evans, M.K. (Michele), Faul, J.D. (Jessica D), Feenstra, B. (Bjarke), Feitosa, M.F. (Mary Furlan), Foisy, S. (Sylvain), Franke, A. (Andre), Friedlander, Y. (Yechiel), Gasparini, P. (Paolo), Gieger, C. (Christian), Gonzalez, C. (Clicerio), Goyette, P. (Philippe), Grant, S.F.A. (Struan), Griffiths, L.R. (Lyn R), Groop, L. (Leif), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hakonarson, H. (Hakon), Hamsten, A. (Anders), Harst, P. (Pim) van der, Heng, C.K. (Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), Wilson, J.F. (James), Clark, D.W. (David W), Okada, Y. (Yukinori), Moore, K.H.S. (Kristjan H S), Mason, D. (Dan), Pirastu, N. (Nicola), Gandin, I. (Ilaria), Mattsson, H. (Hannele), Barnes, C.L.K. (Catriona L K), Lin, K. (Kuang), Zhao, J.H. (Jing Hua), Deelen, P. (Patrick), Rohde, R. (Rebecca), Schurmann, C. (Claudia), Guo, X. (Xiuqing), Giulianini, F. (Franco), Zhang, W. (Weihua), Medina-Gomez, M.C. (Carolina), Karlsson, R. (Robert), Bao, Y. (Yanchun), Bartz, T.M. (Traci M), Baumbach, C. (Clemens), Biino, G. (Ginevra), Bixley, M.J. (Matthew J), Brumat, M. (Marco), Chai, J.-F. (Jin-Fang), Corre, T. (Tanguy), Cousminer, D.L. (Diana), Dekker, A.M. (Annelot M), Eccles, D.A. (David A), Eijk, K.R. (Kristel) van, Fuchsberger, C. (Christian), Gao, H. (He), Germain, M. (Marine), Gordon, S.D. (Scott D.), de Haan, H.G. (Hugoline G), Harris, S.E. (Sarah), Hofer, E. (Edith), Huerta-Chagoya, A. (Alicia), Igartua, C. (Catherine), Jansen, I. (Iris), Jia, Y. (Yucheng), Kacprowski, T. (Tim), Karlsson, T. (Torgny), Kleber, M.E. (Marcus), Li, S.A. (Shengchao Alfred), Li-Gao, R. (Ruifang), Mahajan, A. (Anubha), Matsuda, K. (Koichi), Meidtner, K. (Karina), Meng, W. (Weihua), Montasser, M.E. (May E.), Most, P.J. (Peter) van der, Munz, M. (Matthias), Nutile, T. (Teresa), Palviainen, T. (Teemu), Prasad, G. (Gauri), Prasad, R.B. (Rashmi B), Priyanka, T.D.S. (Tallapragada Divya Sri), Rizzi, F. (Federica), Salvi, E. (Erika), Sapkota, B.R. (Bishwa R), Shriner, D. (Daniel), Skotte, L. (Line), Smart, M.C. (Melissa C), Smith, A.V. (Albert), Spek, A. (Ashley) van der, Spracklen, C.N. (Cassandra N), Strawbridge, R.J. (Rona), Tajuddin, S.M. (Salman M), Trompet, S. (Stella), Turman, C. (Constance), Verweij, N. (Niek), Viberti, C. (Clara), Wang, L. (Lihua), Warren, H. (Helen), Wootton, R.E. (Robyn E), Yanek, L.R. (Lisa), Yao, J. (Jie), Yousri, N.A. (Noha A), Zhao, W. (Wei), Adeyemo, A.A. (Adebowale A), Afaq, S. (Saima), Aguilar-Salinas, C.A. (Carlos Alberto), Akiyama, M. (Masato), Albert, M.L. (Matthew L), Allison, M.A. (Matthew A), Alver, M. (Maris), Aung, T. (Tin), Azizi, J. (Joshan), Bentley, A.R. (Amy), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Borja, J.B. (Judith B), Borst, G.J. (Gert) de, Bottinger, E.P. (Erwin), Broer, L. (Linda), Campbell, H. (Harry), Chanock, S.J. (Stephen), Chee, M.-L. (Miao-Li), Chen, G. (Guanjie), Chen, Y.-D.I. (Yii-Der I), Chen, Z. (Zhengming), Chiu, Y.-F. (Yen-Feng), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Concas, M.P. (Maria Pina), Corley, J. (Janie), Cugliari, G. (Giovanni), Dam, R.M. (Rob) van, Damulina, A. (Anna), Daneshpour, M.S. (Maryam S), Day, F.R. (Felix), Delgado, G., Dhana, K. (Klodian), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Doumatey, A. (Ayo), Dzimiri, N. (Nduna), Ebenesersdóttir, S.S. (S Sunna), Elliott, J. (Joshua), Elliott, P. (Paul), Ewert, R. (Ralf), Felix, J.F. (Janine), Fischer, K. (Krista), Freedman, B.I. (Barry), Girotto, S., Goel, A. (Anuj), Gögele, M. (Martin), Goodarzi, M. (Mark), Graff, M.J. (Maud J.L.), Granot-Hershkovitz, E. (Einat), Grodstein, F. (Francine), Guarrera, S. (Simonetta), Gudbjartsson, D.F. (Daniel), Guity, K. (Kamran), Gunnarsson, B. (Bjarni), Guo, Y. (Yu), Hagenaars, S.P. (Saskia P), Haiman, C.A. (Christopher), Halevy, A. (Avner), Harris, T.B. (Tamara B), Hedayati, M. (Mehdi), Heel, D.A. (David) van, Hirata, M. (Makoto), Höfer, I. (Imo), Hsiung, C.A. (Chao Agnes), Huang, J. (Jinyan), Hung, Y.-J. (Yi-Jen), Ikram, M.A. (Arfan), Jagadeesan, A. (Anuradha), Jousilahti, P. (Pekka), Kamatani, Y. (Yoichiro), Kanai, M. (Masahiro), Kerrison, N.D. (Nicola D), Kessler, T. (Thorsten), Khaw, K.-T. (Kay-Tee), Khor, C.C., Kleijn, D.P.V. (Dominique) de, Koh, W.-P. (Woon-Puay), Kolcic, I. (Ivana), Kraft, P. (Peter), Krämer, B.K. (Bernhard), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lawlor, D.A. (Debbie), Lee, I.-T. (I-Te), Lee, W.-J. (Wen-Jane), Lerch, M. (M.), Li, L. (Liming), Liu, J. (Jianjun), Loh, M. (Marie), London, S.J. (Stephanie J), Loomis, S.J. (Stephanie J.), Lu, Y. (Yingchang), Luan, J. (Jian’an), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W), Manunta, P. (Paolo), Masson, G. (Gisli), Matoba, N. (Nana), Mei, X.W. (Xue W), Meisinger, C. (Christa), Meitinger, T. (Thomas), Mezzavilla, M. (Massimo), Milani, L. (Lili), Millwood, I.Y. (Iona), Momozawa, Y. (Yukihide), Moore, A. (Amy), Morange, P.-E. (P.), Moreno-Macías, H. (Hortensia), Mori, T.A. (Trevor A), Morrison, A.C. (Alanna), Muka, T. (Taulant), Murakami, Y. (Yoshinori), Murray, A.D. (Alison D), Mutsert, R. (Reneé) de, Mychaleckyj, J.C. (Josyf), Nalls, M.A. (Michael), Nauck, M. (Matthias), Neville, M.J. (Matthew), Nolte, I.M. (Ilja), Ong, K.K. (Ken K), Orozco, L. (Lorena), Padmanabhan, S. (Sandosh), Pálsson, G. (Gunnar), Palmer, C.N.A. (Colin), Penninx, B.W.J.H., Pattie, A. (Alison), Polasek, O. (Ozren), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter P), Quintana-Murci, L. (Lluis), Räikkönen, K. (Katri), Ralhan, S. (Sarju), Rao, D.C. (Dabeeru C), Rheenen, W. (Wouter) van, Rich, S.S. (Stephen), Ridker, P.M. (Paul M), Rietveld, C.A. (Cornelius A), Robino, A. (Antonietta), Rooij, F.J.A. (Frank) van, Ruggiero, D., Saba, Y. (Yasaman), Sabanayagam, C. (Charumathi), Sabater-Lleal, M. (Maria), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sandow, K. (Kevin), Schmidt, H. (Helena), Scott, L.J. (Laura J), Scott, W.R. (William R), Sedaghati-Khayat, B. (Bahareh), Sennblad, B. (Bengt), Setten, J. (Jessica) van, Sever, P.J. (Peter J), Sheu, W.H.-H. (Wayne H-H), Shi, Y. (Yuan), Shrestha, S. (Smeeta), Shukla, S.R. (Sharvari Rahul), Sigurdsson, J.K. (Jon K), Sikka, T.T. (Timo Tonis), Singh, J.R. (Jai Rup), Smith, B.H. (Blair), Stancáková, A. (Alena), Stanton, A. (Alice), Starr, J.M. (John), Stefansdottir, L. (Lilja), Straker, L. (Leon), Sulem, P. (Patrick), Sveinbjornsson, G. (Gardar), Swertz, M.A. (Morris A), Taylor, A.M. (Adele M), Taylor, K.D. (Kent), Terzikhan, N. (Natalie), Tham, Y.-C. (Yih-Chung), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tillander, A. (Annika), Tracy, R.P. (Russell), Tusié-Luna, T. (Teresa), Tzoulaki, I., Vaccargiu, S. (Simona), Vangipurapu, J. (Jagadish), Veldink, J.H. (Jan), Vitart, V. (Veronique), Völker, U. (Uwe), Vuoksimaa, E. (Eero), Wakil, S.M. (Salma M), Waldenberger, M. (Melanie), Wander, G.S. (Gurpreet S), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Wild, S.H. (Sarah), Yajnik, C.S. (Chittaranjan S), Yuan, J.-M. (Jian-Min), Zeng, L. (Lingyao), Zhang, L. (Liang), Zhou, J. (Jie), Amin, N. (Najaf), Asselbergs, F.W. (Folkert), Bakker, S.J.L. (Stephan), Becker, D.M. (Diane), Lehne, B. (Benjamin), Bennett, D.A. (David), Berg, L.H. (Leonard) van den, Berndt, S.I. (Sonja), Bharadwaj, D. (Dwaipayan), Bielak, L.F. (Lawrence F.), Bochud, M. 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(Chew-Kiat), Hicks, A.A. (Andrew A), Hochner, H., Huikuri, H.V. (Heikki), Hunt, S.C. (Steven), Jaddoe, V.W.V. (Vincent), De Jager, P., Johannesson, M. (Magnus), Johansson, A. (Åsa), Jonas, J.B. (Jost B), Jukema, J.W. (Jan Wouter), Junttila, M.J. (Juhani), Kaprio, J. (Jaakko), Kardia, S.L.R. (Sharon), Karpe, F. (Fredrik), Kumari, M. (Meena), Laakso, M. (Markku), van der Laan, S.W. (Sander W), Lahti, J. (Jari), Laudes, M. (Matthias), Lea, R.A. (Rodney A), Lieb, W. (Wolfgang), Lumley, T. (Thomas), Martin, N.G. (Nicholas), Ye, S. (Shu), Matullo, G., McCarthy, M.I. (Mark), Medland, S.E. (Sarah), Merriman, A., Metspalu, A. (Andres), Meyer, B.F. (Brian F), Mohlke, K.L. (Karen L), Montgomery, G.W. (Grant), Mook-Kanamori, D. (Dennis), Munroe, P. (Patricia), North, K.E. (Kari), Nyholt, D.R. (Dale), O’connell, J.R. (Jeffery R), Ober, C. (Carole), Oldehinkel, A.J. (Albertine), Palmas, W. (Walter), Pasterkamp, G.G. (Gerard G), Patin, E. (Etienne), Pennell, C.E. (Craig), Perusse, L. (Louis), Peyser, P.A. (Patricia A.), Pirastu, M. (Mario), Polderman, T.J.C. (Tinca), Porteous, D.J. (David J.), Posthuma, D. (Danielle), Psaty, B.M. (Bruce M), Rioux, J.D. (John), Rivadeneira, F. (Fernando), Rotimi, C. (Charles), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruijter, H.M. (Hester ) den, Sanghera, D.K. (Dharambir K), Sattar, N. (Naveed), Schmidt, R. (Reinhold), Schulze, M.B. (Matthias), Schunkert, H. (Heribert), Scott, R.A. (Robert), Shuldiner, A.R. (Alan R), Sim, X. (Xueling), Small, N. (Neil), Smith, J.A. (Jennifer A), Sotoodehnia, N. (Nona), Tai, E.-S. (E-Shyong), Teumer, A. (Alexander), Timpson, N.J. (Nicholas), Toniolo, D. (Daniela), Tregouet, D.-A. (David-Alexandre), Tuomi, T. (Tiinamaija), Vollenweider, P. (Peter), Wang, C.A. (Carol A), Weir, D.R. (David R), Whitfield, J. (John), Wijmenga, C. (Cisca), Wong, T.-Y. (Tien-Yin), Wright, J. (John), Yang, J. (Jingyun), Yu, L. (Lei), Zemel, B.S. (Babette S.), Zonderman, A.B. (Alan B), Perola, M. (Markus), Magnusson, P.K. (Patrik), Uitterlinden, A.G. (André), Kooner, J.S. (Jaspal S.), Chasman, D.I. (Daniel), Loos, R.J.F. (Ruth), Franceschini, N. (Nora), Franke, L. (Lude), Haley, C. (Chris), Hayward, C. (Caroline), Walters, R.G. (Robin G), Perry, J.R.B. (John R. B.), Esko, T. (Tõnu), Helgason, A. (Agnar), Zwart, J-A. (John-Anker), Joshi, P.K. (Peter), Kubo, M. (Michiaki), and Wilson, J.F. (James)
Abstract: In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
Published: 2019
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56. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author: Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gandin, I. (Ilaria), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), Hartwig, F.P. (Fernando P.), He, M. (Meian), Horimoto, A.R.V.R. (Andrea R V R), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Lee, J.H. (Joseph H.), Luan, J. (Jian'an), Lyytikäinen, L.-P. (Leo-Pekka), Matoba, N. (Nana), Nolte, I.M. (Ilja), Pietzner, M. (Maik), Riaz, M. (Muhammad), Said, M.A. (M Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Ballantyne, C. (Christie), Boerwinkle, E.A. (Eric), Broeckel, U. (Ulrich), Campbell, A. (Archie), Canouil, M. (Mickaël), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J. (John), Faire, U. (Ulf) de, de Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, de Silva, H.J. (H Janaka), Ding, J. (Jingzhong), Dominiczak, A.F. (Anna F.), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Eppinga, R.N. (Ruben N.), Faul, J.D. (Jessica D.), Fisher, V. (Virginia), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Ghanbari, M. (Mohsen), Giulianini, F. (Franco), Grabe, H.J. (Hans Jörgen), Grove, M.L. (Megan), Gu, C. (Charles), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Hixson, J.E. (James E.), Howard, B.V. (Barbara V.), Ikram, M.A. (Arfan), Jacobs, D.R. (David R.), Johnson, C. (Craig), Jonas, J.B., Kammerer, C.M. (Candace), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas O.), Koh, W.-P. (Woon-Puay), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kooperberg, C. (Charles), Krieger, J.E. (José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. (Antonietta), Robinson, J.G. (Jennifer), Rose, L.M. (Lynda M.), Rudan, I. (Igor), Schmidt, C.O. (Carsten O.), Schreiner, P.J. (Pamela), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Smith, B.H. (Blair), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Tan, N. (Nicholas), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Uitterlinden, A.G. (André), Heemst, D. (Diana) van, Vuckovic, D. (Dragana), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y. (Yujie), Wang, Z. (Zhe), Wei, W.B. (Wen Bin), Williams, C. (Christine), Wilson, G. (Gregory), Wojczynski, M.K. (Mary ), Yao, J. (Jie), Yu, B. (Bing), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Horta, B.L. (Bernardo L.), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Laakso, M. (Markku), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Penninx, B.W.J.H. (Brenda), Pereira, A.C. (Alexandre C.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Wagenknecht, L.E. (Lynne), Wang, Y.X. (Ya Xing), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda R.), Zheng, W. (Wei), Elliott, P. (Paul), North, K.E. (Kari), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Liu, C.-T. (Ching-Ti), Liu, Y. (YongMei), Psaty, B.M. (Bruce M.), Jarvelin, M.-R. (Marjo-Riitta), Dam, R.M. (Rob) van, Kardia, S.L.R. (Sharon), Dominiczak, A. (Anna), Rotimi, C. (Charles), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), Morrison, A.C. (Alanna), Vries, P.S. (Paul) de, Brown, M.R., Bentley, A.R. (Amy), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Schwander, K., Kraja, A. (Aldi), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Huffman, J.E. (Jennifer E.), Musani, S.K. (Solomon K.), Li, C. (Changwei), Feitosa, M.F. (Mary Furlan), Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Deng, X. (Xuan), Dorajoo, R. (Rajkumar), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Evangelou, E. (Evangelos), Graff, M.J. (Maud J.L.), Alver, M. (Maris), Boissel, M. (Mathilde), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. 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(José), Kritchevsky, S.B. (Steve B.), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lemaitre, R.N. (Rozenn ), Li, Y. (Yize), Liang, J. (Jingjing), Liu, J. (Jianjun), Liu, K. (Kiang), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), Manichaikul, A.W. (Ani W.), McKenzie, C.A. (Colin A.), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen L.), Mosley, T.H. (Thomas H.), Mukamal, K. (Kenneth), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), O´Connell, J.R., Palmer, N.D. (Nicholette), Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Reiner, A.P. (Alex P.), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Robino, A. 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(Ervin R.), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (Shyong), Wong, T.Y. (Tien Yin), Liu, J. (Jingmin), Rotter, J.I. (Jerome I.), Gauderman, W.J. (W James), Province, M.A. (Michael A.), Munroe, P. (Patricia), Rice, K. (Kenneth), Chasman, D.I. (Daniel), Cupples, L.A. (L Adrienne), Tobin, M.D. (Martin), and Morrison, A.C. (Alanna)
Abstract: A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
Published: 2019
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57. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Bentley, A.R. (Amy), Noordam, R., Sung, YJ, Schwander, K., Winkler, T.W. (Thomas), Jakupovic, H., Chasman, D.I. (Daniel), Manning, A., Ntalla, I. (Ioanna), Aschard, H. (Hugues), Brown, M.R., de Las Fuentes, L., Franceschini, N. (Nora), Guo, X. (Xiuqing), Vojinovic, D., Aslibekyan, S, Feitosa, M.F. (Mary Furlan), Kho, M., Musani, SK, Richard, M., Wang, H.M., Wang, Z. (Zhen), Bartz, TM, Bielak, L.F. (Lawrence F.), Campbell, A. (Archie), Dorajoo, R. (Rajkumar), Fisher, V., Hartwig, F.P., Horimoto, A., Li, C.W., Lohman, K. (Kurt), Marten, J, Sim, XL, Smith, A.V. (Davey), Tajuddin, S. M., Alver, M, Amini, M., Boissel, M., Chai, J.F., Chen, X. (Xishu), Divers, J, Evangelou, E. (Evangelos), Gao, C. (Cheng), Graff, M.J. (Maud J.L.), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Zhao, J.H. (Jing Hua), Kraja, A. (Aldi), Kuhnel, B. (Brigitte), Laguzzi, F., Lyytikäinen, L.-P. (Leo-Pekka), Nolte, IM, Rauramaa, R. (Rainer), Riaz, M. (Muhammad), Robino, A. (Antonietta), Rueedi, R, Stringham, H.M. (Heather), Takeuchi, F, Most, P.J. (Peter) van der, Varga, T.V. (Tibor), Verweij, N. (Niek), Ware, EB, Wen, WQ, Li, X. Y., Yanek, L.R. (Lisa), Amin, N. (Najaf), Arnett, D.K. (Donna), Boerwinkle, E.A. (Eric), Brumat, M., Cade, B, Canouil, M., Chen, Y.D.I. (Yii-Der Ida), Concas, MP, Connell, J. (John), Mutsert, R. (Reneé) de, de Silva, H.J., de Vries, PS, Demirkan, A. (Ayşe), Ding, J. (Jingzhong), Eaton, CB, Faul, J.D. (Jessica), Friedlander, Y. (Yechiel), Gabriel, K.P., Ghanbari, M., Giulianini, F. (Franco), Gu, C.C., Gu, DF, Harris, T.B. (Tamara), He, J. (Jing), Heikkinen, S., Heng, C.K. (Chew-Kiat), Hunt, S.C. (Steven), Ikram, M.A. (Arfan), Jonas, J.B., Koh, WP, Komulainen, P. (Pirjo), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, LJ, Leander, K. (Karin), Lemaitre, R.N. (Rozenn ), Lewis, CE, Liang, J.J., Alizadeh, BZ, Boezen, H.M. (Marike), Franke, L. (Lude), Navis, G. (Gerjan), Rots, M., Swertz, M. (Morris), Wolffenbuttel, B.H.R. (Bruce), Wijmenga, C. (Cisca), Liu, J. (Jianjun), Maagi, R., Manichaikul, A. (Ani), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Mohlke, K.L. (Karen), Mosley, T.H. (Thomas), Murray, A.D., Nalls, M.A. (Michael), Nang, EEK, Nelson, C.P. (Christopher), Nona, S., Norris, JM, Nwuba, C.V., O´Connell, J.R., Palmer, N.D. (Nicholette), Papanicolau, GJ, Pazoki, R. (Raha), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Polasek, O. (Ozren), Porteous, D.J. (David J.), Poveda, A. (Andrés), Raitakari, OT, Rich, S.S. (Stephen), Risch, N., Robinson, JG, Rose, L.M. (Lynda), Rudan, I. (Igor), Schreiner, PJ, Scott, L.J. (Laura), Sidney, SS, Sims, M, Smith, J.A. (Jennifer A), Snieder, H. (Harold), Sofer, T., Starr, J.M. (John), Sternfeld, B., Strauch, K. (Konstantin), Tang, H. (Hui), Taylor, K.D. (Kent), Tsai, M.Y. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), van der Ende, M.Y., Heemst, D. van, Voortman, R.G. (Trudy), Waldenberger, M. (Melanie), Wennberg, P. (Patrik), Wilson, G, Xiang, YB, Yao, J, Yu, C.Z., Yuan, JM, Zhao, W. (Wei), Zonderman, A.B. (Alan), Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, DW, Faire, U. (Ulf) de, Deary, I.J. (Ian), Elliott, P.M. (Perry), Esko, T. (Tõnu), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Kato, N, Laakso, M. (Markku), Lakka, T.A. (Timo), Lehtimaki, T, Magnusson, P.K. (Patrik), Oldenhinkel, A.J. (A.), Penninx, B.W.J.H. (Brenda), Samani, N.J. (Nilesh), Shu, X.-O. (Xiao-Ou), Harst, P. (Pim) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wang, Y. (Ying), Wareham, N.J. (Nick), Weir, D.R. (David), Wu, TC, Zheng, W. (Wei), Zhu, X. (Xiaofeng), Evans, MK, Franks, P.W. (Paul), Guonason, V. (Vilmundur), Hayward, C. (Caroline), Horta, BL, Kelly, TN, Liu, Y. (YongMei), North, K.E. (Kari), Pereira, AC, Ridker, P.M. (Paul), Tai, E.S. (Shyong), Dam, R.M. (Rob) van, Fox, E.R. (Ervin), Kardia, S.L.R. (Sharon), Liu, C.-T. (Ching-Ti), Mook-Kanamori, D.O. (Dennis), Province, M.A. (Mike), Redline, S. (Susan), Duijn, C.M., Rotter, J.I. (Jerome), Kooperberg, C.B., Gauderman, W.J. (W James), Psaty, B.M. (Bruce), Rice, K, Munroe, P. (Patricia), Fornage, M. (Myriam), Cupples, L.A. (Adrienne), Rotimi, CN, Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), and Loos, R.J.F. (Ruth)
Abstract: Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 l
Published: 2019
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58. What is the risk of mortality for people who are screen positive in a diabetes screening programme but who do not have diabetes on biochemical testing? Diabetes screening programmes from a public health perspective. (Original Paper)

Author: Spijkerman, A., Griffin, S., Dekker, J., Nijpels, G., and Wareham, N.J.
Subjects: Questionnaires -- Usage -- Evaluation -- Methods, Mortality -- Netherlands, Type 2 diabetes -- Risk factors -- Diagnosis -- Patient outcomes, Medical screening -- Methods -- Usage -- Evaluation, Health, Social sciences
Abstract: Objectives: To assess mortality risk in people classified by the Cambridge risk score (CRS), a previously validated simple screening tool for undiagnosed type 2 diabetes that uses only information routinely [...]
Published: 2002

59. The performance of a risk score in predicting undiagnosed hyperglycemia. (Epidemiology/Health Services/Psychosocial Research)

Author: Park, P.J., Griffin, S.J., Sargeant, L., and Wareham, N.J.
Subjects: Diabetes -- Research, Type 2 diabetes -- Diagnosis, Health, Diagnosis
Abstract: OBJECTIVE -- Type 2 diabetes is a serious disease that is commonly undetected and for which screening is sometimes advocated. A number of risk factors are associated with prevalent undiagnosed [...]
Published: 2002

60. Variants in the APOC3 promoter insulin responsive element modulate insulin secretion and lipids in middle-aged men

Author: Waterworth, D.M., Talmud, P.J., Luan, J., Flavell, D.M., Byrne, C.D., Humphries, S.E., and Wareham, N.J.
Published: 2003
Full Text: View/download PDF

61. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author: Jiang, X., O'Reilly, P.F., Aschard, H., Hsu, Y.H., Richards, J.B., Dupuis, J., Ingelsson, E., Karasik, D., Pilz, S., Berry, D., Kestenbaum, B., Zheng, J.S., Luan, J.N., Sofianopoulou, E., Streeten, E.A., Albanes, D., Lutsey, P.L., Yao, L., Tang, W.H., Econs, M.J., Wallaschofski, H., Volzke, H., Zhou, A., Power, C., McCarthy, M.I., Michos, E.D., Boerwinkle, E., Weinstein, S.J., Freedman, N.D., Huang, W.Y., Schoor, N.M. van, Velde, N. van der, Groot, L.C.P.G.M. de, Enneman, A., Cupples, L.A., Booth, S.L., Vasan, R.S., Liu, C.T., Zhou, Y.H., Ripatti, S., Ohlsson, C., Vandenput, L., Lorentzon, M., Eriksson, J.G., Shea, M.K., Houston, D.K., Kritchevsky, S.B., Liu, Y.M., Lohman, K.K., Ferrucci, L., Peacock, M., Gieger, C., Beekman, M., Slagboom, E., Deelen, J., Heemst, D. van, Kleber, M.E., Marz, W., Boer, I.H. de, Wood, A.C., Rotter, J.I., Rich, S.S., Robinson-Cohen, C., Heijer, M. den, Jarvelin, M.R., Cavadino, A., Joshi, P.K., Wilson, J.F., Hayward, C., Lind, L., Michaelsson, K., Trompet, S., Zillikens, M.C., Uitterlinden, A.G., Rivadeneira, F., Broer, L., Zgaga, L., Campbell, H., Theodoratou, E., Farrington, S.M., Timofeeva, M., Dunlop, M.G., Valdes, A.M., Tikkanen, E., Lehtimaki, T., Lyytikainen, L.P., Kahonen, M., Raitakari, O.T., Mikkila, V., Ikram, M.A., Sattar, N., Jukema, J.W., Wareham, N.J., Langenberg, C., Forouhi, N.G., Gundersen, T.E., Khaw, K.T., Butterworth, A.S., Danesh, J., Spector, T., Wang, T.J., Hypponen, E., Kraft, P., and Kiel, D.P.
Published: 2018

62. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps

Author: Mahajan, A. Taliun, D. Thurner, M. Robertson, N.R. Torres, J.M. Rayner, N.W. Payne, A.J. Steinthorsdottir, V. Scott, R.A. Grarup, N. Cook, J.P. Schmidt, E.M. Wuttke, M. Sarnowski, C. Mägi, R. Nano, J. Gieger, C. Trompet, S. Lecoeur, C. Preuss, M.H. Prins, B.P. Guo, X. Bielak, L.F. Below, J.E. Bowden, D.W. Chambers, J.C. Kim, Y.J. Ng, M.C.Y. Petty, L.E. Sim, X. Zhang, W. Bennett, A.J. Bork-Jensen, J. Brummett, C.M. Canouil, M. Ec kardt, K.-U. Fischer, K. Kardia, S.L.R. Kronenberg, F. Läll, K. Liu, C.-T. Locke, A.E. Luan, J. Ntalla, I. Nylander, V. Schönherr, S. Schurmann, C. Yengo, L. Bottinger, E.P. Brandslund, I. Christensen, C. Dedoussis, G. Florez, J.C. Ford, I. Franco, O.H. Frayling, T.M. Giedraitis, V. Hackinger, S. Hattersley, A.T. Herder, C. Ikram, M.A. Ingelsson, M. Jørgensen, M.E. Jørgensen, T. Kriebel, J. Kuusisto, J. Ligthart, S. Lindgren, C.M. Linneberg, A. Lyssenko, V. Mamakou, V. Meitinger, T. Mohlke, K.L. Morris, A.D. Nadkarni, G. Pankow, J.S. Peters, A. Sattar, N. Stančáková, A. Strauch, K. Taylor, K.D. Thorand, B. Thorleifsson, G. Thorsteinsdottir, U. Tuomilehto, J. Witte, D.R. Dupuis, J. Peyser, P.A. Zeggini, E. Loos, R.J.F. Froguel, P. Ingelsson, E. Lind, L. Groop, L. Laakso, M. Collins, F.S. Jukema, J.W. Palmer, C.N.A. Grallert, H. Metspalu, A. Dehghan, A. Köttgen, A. Abecasis, G.R. Meigs, J.B. Rotter, J.I. Marchini, J. Pedersen, O. Hansen, T. Langenberg, C. Wareham, N.J. Stefansson, K. Gloyn, A.L. Morris, A.P. Boehnke, M. McCarthy, M.I.
Abstract: We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency 2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence). © 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
Published: 2018

63. Consumption of fruits, vegetables and fruit juices and differentiated thyroid carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Zamora-Ros, R. Béraud, V. Franceschi, S. Cayssials, V. Tsilidis, K.K. Boutron-Ruault, M.-C. Weiderpass, E. Overvad, K. Tjønneland, A. Eriksen, A.K. Bonnet, F. Affret, A. Katzke, V. Kühn, T. Boeing, H. Trichopoulou, A. Valanou, E. Karakatsani, A. Masala, G. Grioni, S. Santucci de Magistris, M. Tumino, R. Ricceri, F. Skeie, G. Parr, C.L. Merino, S. Salamanca-Fernández, E. Chirlaque, M.-D. Ardanaz, E. Amiano, P. Almquist, M. Drake, I. Hennings, J. Sandström, M. Bueno-de-Mesquita, H.B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Schmidt, J.A. Perez-Cornago, A. Aune, D. Riboli, E. Slimani, N. Scalbert, A. Romieu, I. Agudo, A. Rinaldi, S.
Abstract: Fruit and vegetable (F&V) intake is considered as probably protective against overall cancer risk, but results in previous studies are not consistent for thyroid cancer (TC). The purpose of this study is to examine the association between the consumption of fruits, vegetables, fruit juices and differentiated thyroid cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The EPIC study is a cohort including over half a million participants, recruited between 1991 and 2000. During a mean follow-up of 14 years, 748 incident first primary differentiated TC cases were identified. F&V and fruit juice intakes were assessed through validated country-specific dietary questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models adjusted for potential confounding factors. Comparing the highest versus lowest quartile of intake, differentiated TC risk was not associated with intakes of total F&V (HR: 0.89; 95% CI: 0.68–1.15; p-trend = 0.44), vegetables (HR: 0.89; 95% CI: 0.69–1.14; p-trend = 0.56), or fruit (HR: 1.00; 95% CI: 0.79–1.26; p-trend = 0.64). No significant association was observed with any individual type of vegetable or fruit. However, there was a positive borderline trend with fruit juice intake (HR: 1.23; 95% CI: 0.98–1.53; p-trend = 0.06). This study did not find any significant association between F&V intakes and differentiated TC risk; however a positive trend with fruit juice intake was observed, possibly related to its high sugar content. © 2017 UICC
Published: 2018

64. Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes article

Author: Mahajan, A. Wessel, J. Willems, S.M. Zhao, W. Robertson, N.R. Chu, A.Y. Gan, W. Kitajima, H. Taliun, D. Rayner, N.W. Guo, X. Lu, Y. Li, M. Jensen, R.A. Hu, Y. Huo, S. Lohman, K.K. Zhang, W. Cook, J.P. Prins, B.P. Flannick, J. Grarup, N. Trubetskoy, V.V. Kravic, J. Kim, Y.J. Rybin, D.V. Yaghootkar, H. Müller-Nurasyid, M. Meidtner, K. Li-Gao, R. Varga, T.V. Marten, J. Li, J. Smith, A.V. An, P. Ligthart, S. Gustafsson, S. Malerba, G. Demirkan, A. Tajes, J.F. Steinthorsdottir, V. Wuttke, M. Lecoeur, C. Preuss, M. Bielak, L.F. Graff, M. Highland, H.M. Justice, A.E. Liu, D.J. Marouli, E. Peloso, G.M. Warren, H.R. Afaq, S. Afzal, S. Ahlqvist, E. Bang, L.B. Bertoni, A.G. Bombieri, C. Bork-Jensen, J. Brandslund, I. Brody, J.A. Burtt, N.P. Canouil, M. Chen, Y.-D.I. Cho, Y.S. Christensen, C. Eastwood, S.V. Eckardt, K.-U. Fischer, K. Gambaro, G. Giedraitis, V. Grove, M.L. De Haan, H.G. Hackinger, S. Hai, Y. Han, S. Tybjærg-Hansen, A. Hivert, M.-F. Isomaa, B. Jäger, S. Jørgensen, M.E. Jørgensen, T. Käräjämäki, A. Kim, B.-J. Kim, S.S. Koistinen, H.A. Kovacs, P. Kriebel, J. Kronenberg, F. Läll, K. Lange, L.A. Lee, J.-J. Lehne, B. Li, H. Lin, K.-H. Linneberg, A. Liu, C.-T. Liu, J. Loh, M. Mägi, R. Mamakou, V. McKean-Cowdin, R. Nadkarni, G. Neville, M. Nielsen, S.F. Ntalla, I. Peyser, P.A. Rathmann, W. Rice, K. Rich, S.S. Rode, L. Rolandsson, O. Schönherr, S. Selvin, E. Small, K.S. Stančáková, A. Surendran, P. Taylor, K.D. Teslovich, T.M. Thorand, B. Thorleifsson, G. Tin, A. Tönjes, A. Varbo, A. Witte, D.R. Wood, A.R. Yajnik, P. Yao, J. Yengo, L. Young, R. Boeing, H. Boerwinkle, E. Bottinger, E.P. Chowdhury, R. Dedoussis, G. Dehghan, A. Deloukas, P. Ferrario, M.M. Ferrières, J. Florez, J.C. Frossard, P. Gudnason, V. Harris, T.B. Heckbert, S.R. Howson, J.M.M. Ingelsson, M. Kathiresan, S. Kee, F. Kuusisto, J. Langenberg, C. Launer, L.J. Lindgren, C.M. Männistö, S. Meitinger, T. Mohlke, K.L. Moitry, M. Morris, A.D. Murray, A.D. De Mutsert, R. Orho-Melander, M. Owen, K.R. Perola, M. Peters, A. Province, M.A. Rasheed, A. Ridker, P.M. Rivadineira, F. Rosendaal, F.R. Rosengren, A.H. Salomaa, V. Sheu, W.H.-H. Sladek, R. Smith, B.H. Strauch, K. Uitterlinden, A.G. Varma, R. Willer, C.J. Blüher, M. Chambers, J.C. Danesh, J. Van Duijn, C. Dupuis, J. Franco, O.H. Franks, P.W. Froguel, P. Grallert, H. Groop, L. Han, B.-G. Hansen, T. Hattersley, A.T. Hayward, C. Ingelsson, E. Kardia, S.L.R. Karpe, F. Kooner, J.S. Köttgen, A. Kuulasmaa, K. Laakso, M. Lin, X. Lind, L. Liu, Y. Loos, R.J.F. Marchini, J. Metspalu, A. Mook-Kanamori, D. Nordestgaard, Bø.G. Palmer, C.N.A. Pankow, J.S. Pedersen, O. Psaty, B.M. Rauramaa, R. Sattar, N. Schulze, M.B. Soranzo, N. Spector, T.D. Stefansson, K. Stumvoll, M. Thorsteinsdottir, U. Tuomi, T. Tuomilehto, J. Wareham, N.J. Wilson, J.G. Zeggini, E. Scott, R.A. Barroso, I. Frayling, T.M. Goodarzi, M.O. Meigs, J.B. Boehnke, M. Saleheen, D. Morris, A.P. Rotter, J.I. McCarthy, M.I. ExomeBP Consortium MAGIC Consortium GIANT Consortium
Abstract: We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition. © 2018 The Author(s).
Published: 2018

65. Dietary intake of total polyphenol and polyphenol classes and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Zamora-Ros, R. Cayssials, V. Jenab, M. Rothwell, J.A. Fedirko, V. Aleksandrova, K. Tjønneland, A. Kyrø, C. Overvad, K. Boutron-Ruault, M.-C. Carbonnel, F. Mahamat-Saleh, Y. Kaaks, R. Kühn, T. Boeing, H. Trichopoulou, A. Valanou, E. Vasilopoulou, E. Masala, G. Pala, V. Panico, S. Tumino, R. Ricceri, F. Weiderpass, E. Lukic, M. Sandanger, T.M. Lasheras, C. Agudo, A. Sánchez, M.-J. Amiano, P. Navarro, C. Ardanaz, E. Sonestedt, E. Ohlsson, B. Nilsson, L.M. Rutegård, M. Bueno-de-Mesquita, B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Bradbury, K. Freisling, H. Romieu, I. Cross, A.J. Vineis, P. Scalbert, A.
Subjects: food and beverages
Abstract: Polyphenols may play a chemopreventive role in colorectal cancer (CRC); however, epidemiological evidence supporting a role for intake of individual polyphenol classes, other than flavonoids is insufficient. We evaluated the association between dietary intakes of total and individual classes and subclasses of polyphenols and CRC risk and its main subsites, colon and rectum, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The cohort included 476,160 men and women from 10 European countries. During a mean follow-up of 14 years, there were 5991 incident CRC cases, of which 3897 were in the colon and 2094 were in the rectum. Polyphenol intake was estimated using validated centre/country specific dietary questionnaires and the Phenol-Explorer database. In multivariable-adjusted Cox regression models, a doubling in total dietary polyphenol intake was not associated with CRC risk in women (HR log2 = 1.06, 95% CI 0.99–1.14) or in men (HR log2 = 0.97, 95% CI 0.90–1.05), respectively. Phenolic acid intake, highly correlated with coffee consumption, was inversely associated with colon cancer in men (HR log2 = 0.91, 95% CI 0.85–0.97) and positively associated with rectal cancer in women (HR log2 = 1.10, 95% CI 1.02–1.19); although associations did not exceed the Bonferroni threshold for significance. Intake of other polyphenol classes was not related to colorectal, colon or rectal cancer risks. Our study suggests a possible inverse association between phenolic acid intake and colon cancer risk in men and positive with rectal cancer risk in women. © 2018, Springer Science+Business Media B.V., part of Springer Nature.
Published: 2018

66. Prediction of acute myeloid leukaemia risk in healthy individuals

Author: Abelson, S. Collord, G. Ng, S.W.K. Weissbrod, O. Mendelson Cohen, N. Niemeyer, E. Barda, N. Zuzarte, P.C. Heisler, L. Sundaravadanam, Y. Luben, R. Hayat, S. Wang, T.T. Zhao, Z. Cirlan, I. Pugh, T.J. Soave, D. Ng, K. Latimer, C. Hardy, C. Raine, K. Jones, D. Hoult, D. Britten, A. McPherson, J.D. Johansson, M. Mbabaali, F. Eagles, J. Miller, J.K. Pasternack, D. Timms, L. Krzyzanowski, P. Awadalla, P. Costa, R. Segal, E. Bratman, S.V. Beer, P. Behjati, S. Martincorena, I. Wang, J.C.Y. Bowles, K.M. Quirós, J.R. Karakatsani, A. La Vecchia, C. Trichopoulou, A. Salamanca-Fernández, E. Huerta, J.M. Barricarte, A. Travis, R.C. Tumino, R. Masala, G. Boeing, H. Panico, S. Kaaks, R. Krämer, A. Sieri, S. Riboli, E. Vineis, P. Foll, M. McKay, J. Polidoro, S. Sala, N. Khaw, K.-T. Vermeulen, R. Campbell, P.J. Papaemmanuil, E. Minden, M.D. Tanay, A. Balicer, R.D. Wareham, N.J. Gerstung, M. Dick, J.E. Brennan, P. Vassiliou, G.S. Shlush, L.I.
Subjects: hemic and lymphatic diseases, neoplasms
Abstract: The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure 1 . The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion 2,3 . However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH) 4-8 . Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention. © 2018 Macmillan Publishers Ltd., part of Springer Nature.
Published: 2018

67. Body mass index and body fat distribution and new-onset atrial fibrillation: Substudy of the European Prospective Investigation into Cancer and Nutrition in Norfolk (EPIC-Norfolk) study

Author: Neefs, J., primary, Boekholdt, S.M., additional, Khaw, K.-T., additional, Luben, R., additional, Pfister, R., additional, Wareham, N.J., additional, Meulendijks, E.R., additional, Sanders, P., additional, and de Groot, J.R., additional
Published: 2019
Full Text: View/download PDF

68. Erratum to: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Author: Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), Caulfield, M. (Mark), Evangelou, E. (Evangelos), Warren, H. (Helen), Mosen-Ansorena, D. (David), Mifsud, B. (Borbala), Pazoki, R. (Raha), Gao, H. (He), Ntritsos, G. (Georgios), Dimou, N. (Niki), Cabrera, C.P. (Claudia P.), Karaman, I. (Ibrahim), Ng, F.L. (Fu Liang), Evangelou, M. (Marina), Witkowska, K. (Katarzyna), Tzanis, E. (Evan), Hellwege, J.N. (Jacklyn N.), Giri, A. (Ayush), Velez Edwards, D.R. (Digna R.), Sun, Y.V. (Yan V.), Cho, K. (Kelly), Gaziano, J.M. (J. Michael), Wilson, P.W.F. (Peter W. F.), Tsao, P.S. (Philip S.), Kovesdy, C.P. (Csaba P.), Esko, T. (Tonu), Mägi, R. (Reedik), Milani, L. (Lili), Almgren, P. (Peter), Boutin, T. (Thibaud), Debette, S. (Stéphanie), Ding, J. (Jun), Giulianini, F. (Franco), Holliday, E.G. (Elizabeth), Jackson, A.U. (Anne), Li-Gao, R. (Ruifang), Lin, W.-Y. (Wei-Yu), Luan, J., Mangino, M. (Massimo), Oldmeadow, C. (Christopher), Prins, B.P. (Bram Peter), Qian, Y. (Yong), Sargurupremraj, M. (Muralidharan), Shah, N. (Nisha), Surendran, P. (Praveen), Thériault, S. (Sébastien), Verweij, N. (Niek), Willems, S.M. (Sara), Zhao, J.-H. (Jing-Hua), Amouyel, P. (Philippe), Connell, J. (John), Mutsert, R. (Reneé) de, Doney, A.S.F. (Alex), Farrall, M. (Martin), Menni, C. (Cristina), Morris, A.D. (Andrew), Noordam, R. (Raymond), Pare, G. (Guillame), Poulter, N.R. (Neil), Shields, D.C. (Denis C.), Stanton, A. (Alice), McG Thom, S.A., Abecasis, G. (Gonçalo), Amin, N. (Najaf), Arking, D.E. (Dan), Ayers, K.L. (Kristin), Barbieri, C.M. (Caterina M.), Batini, C. (Chiara), Bis, J.C. (Joshua), Blake, T. (Tineka), Bochud, M. (Murielle), Boehnke, M. (Michael), Boerwinkle, E. (Eric), Boomsma, D.I. (Dorret I.), Bottinger, E.P. (Erwin P.), Braund, P.S. (Peter), Brumat, M. (Marco), Campbell, A. (Archie), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chambers, J.C. (John C.), Chauhan, G. (Ganesh), Ciullo, M. (Marina), Cocca, M. (Massimiliano), Collins, F. (Francis), Cordell, H.J. (Heather), Davies, G. (Gail), de Borst, M.H. (Martin H.), Geus, E.J.C. (Eco) de, Deary, I.J. (Ian), Deelen, J. (Joris), Del Greco M, F. (Fabiola), Demirkale, C.Y. (Cumhur Yusuf), Dörr, M. (Marcus), Ehret, G.B. (Georg B.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erzurumluoglu, A.M. (A. Mesut), Ferreira, T. (Teresa), Frånberg, M. (Mattias), Franco, O.H. (Oscar), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Gieger, C. (Christian), Girotto, G. (Giorgia), Goel, A. (Anuj), Gow, A.J. (Alan J.), Gudnason, V. (Vilmundur), Guo, X. (Xiuqing), Gyllensten, U. (Ulf), Hamsten, A. (Anders), Harris, T.B. (Tamara), Harris, S.E. (Sarah), Hartman, C.A. (Catharina A.), Havulinna, A.S. (Aki), Hicks, A.A. (Andrew A.), Hofer, E. (Edith), Hofman, A. (Albert), Hottenga, J.J. (Jouke Jan), Huffman, J.E. (Jennifer E.), Hwang, S.-J. (Shih-Jen), Ingelsson, E. (Erik), James, A. (Alan), Jansen, R. (Rick), Jarvelin, M.-R. (Marjo-Riitta), Joehanes, R. (Roby), Johansson, A. (Åsa), Johnson, A.D. (Andrew), Joshi, P.K. (Peter K.), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Jula, A. (Antti), Kähönen, M. (Mika), Kathiresan, S. (Sekar), Keavney, B.D. (Bernard D.), Khaw, K.-T. (Kay-Tee), Knekt, P., Knight, J. (Joanne), Kolcic, I. (Ivana), Kooner, J.S. (Jaspal S.), Koskinen, S. (Seppo), Kristiansson, K. (Kati), Kutalik, Z. (Zoltán), Laan, M. (Maris), Larson, M.G. (Martin), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lehtimäki, T. (Terho), Liewald, D.C.M. (David C. M.), Lin, L. (Li), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Liu, Y. (YongMei), Loos, R.J.F. (Ruth), Lopez, L.M. (Lorna), Lu, Y. (Yingchang), Lyytikäinen, L.-P. (Leo-Pekka), Mahajan, A. (Anubha), Mamasoula, C. (Chrysovalanto), Marrugat, J. (Jaume), Marten, J. (Jonathan), Milaneschi, Y. (Yuri), Morgan, A. (Anna), Morris, A.P. (Andrew), Morrison, A.C. (Alanna), Munson, P.J. (Peter), Nalls, M.A. (Michael), Nandakumar, P. (Priyanka), Nelson, C.P. (Christopher P.), Niiranen, T. (Teemu), Nolte, I.M. (Ilja), Nutile, T. (Teresa), Oldehinkel, A.J. (Albertine), Oostra, B.A. (Ben), O’Reilly, P.F. (Paul F.), Org, E. (Elin), Padmanabhan, S. (Sandosh), Palmas, W. (Walter), Palotie, A. (Aarno), Pattie, A. (Alison), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Polasek, O. (Ozren), Pramstaller, P.P. (Peter Paul), Nguyen, Q.T. (Quang Tri), Raitakari, O. (Olli), Ren, M. (Meixia), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Ridker, P.M. (Paul), Ried, J.S. (Janina S.), Riese, H. (Harriëtte), Ripatti, S. (Samuli), Robino, A. (Antonietta), Rose, L.M. (Lynda M.), Rotter, J.I. (Jerome I.), Rudan, I. (Igor), Ruggiero, D., Saba, Y. (Yasaman), Sala, C. (Cinzia), Salomaa, V. (Veikko), Samani, N.J. (Nilesh J.), Sarin, A.-P., Schmidt, R. (Reinhold), Schmidt, H. (Helena), Shrine, N.R.G. (Nick), Siscovick, D. (David), Smith, A.V. (Albert), Snieder, H. (Harold), Sõber, S. (Siim), Sorice, R., Starr, J.M. (John), Stott, D.J. (David. J.), Strachan, D.P. (David), Strawbridge, R.J. (Rona), Sundström, J. (Johan), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Teumer, A. (Alexander), Tobin, M.D. (Martin), Tomaszewski, M. (Maciej), Toniolo, D. (Daniela), Traglia, M. (Michela), Trompet, S. (Stella), Tuomilehto, J. (Jaakko), Tzourio, C. (Christophe), Uitterlinden, A.G. (André), Vaez, A. (Ahmad), Most, P.J. (Peter) van der, Duijn, C.M. (Cornelia) van, Vergnaud, A.-C. (Anne-Claire), Verwoert, G.C. (Germaine C.), Vitart, V. (Veronique), Völker, U. (Uwe), Vollenweider, P. (Peter), Vuckovic, D. (Dragana), Watkins, H. (Hugh), Wild, S.H. (Sarah), Willemsen, G. (Gonneke), Wilson, J.F. (James F.), Wright, A.F. (Alan), Yao, J. (Jie), Zemunik, T. (Tatijana), Zhang, W. (Weihua), Attia, J. (John), Butterworth, A.S. (Adam S.), Chasman, D.I. (Daniel), Conen, D. (David), Cucca, F. (Francesco), Danesh, J. (John), Hayward, C. (Caroline), Howson, J.M.M. (Joanna M. M.), Laakso, M. (Markku), Lakatta, E.G. (Edward G.), Langenberg, C. (Claudia), Melander, O. (Olle), Mook-Kanamori, D.O. (Dennis O.), Palmer, C.N.A. (Colin N. A.), Risch, L. (Lorenz), Scott, R.A. (Robert), Scott, R.J. (Rodney J.), Sever, P. (Peter), Spector, T.D. (Timothy), van der Harst, P. (Pim), Wareham, N.J. (Nick), Zeggini, E. (Eleftheria), Levy, D. (Daniel), Munroe, P. (Patricia), Newton-Cheh, C. (Christopher), Brown, M.J. (Morris), Metspalu, A. (Andres), Hung, A.M. (Adriana M.), Ódonnell, C.J. (Christopher), Edwards, T.L. (Todd L.), Psaty, B.M. (Bruce), Tzoulaki, I., Barnes, M.J. (Michael), Wain, L.V. (Louise V.), Elliott, P. (Paul), and Caulfield, M. (Mark)
Abstract: In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.
Published: 2018
Full Text: View/download PDF

69. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes

Author: Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), Morris, R.W. (Richard), Franceschini, N. (Nora), Giambartolomei, C. (Claudia), Vries, P.S. (Paul) de, Finan, C. (Chris), Bis, J.C. (Joshua), Huntley, R.P. (Rachael P.), Lovering, R.C. (Ruth C.), Tajuddin, S.M. (Salman M.), Winkler, T.W. (Thomas W.), Graff, M. (Misa), Kavousi, M. (Maryam), Dale, C. (Caroline), Smith, A.V. (Albert), Hofer, E. (Edith), Leeuwen, E.M. (Elisa) van, Nolte, I.M. (Ilja), Lu, L. (Lingyi), Scholz, M. (Markus), Sargurupremraj, M. (Muralidharan), Pitkanen, N. (Niina), Franzén, O. (Oscar), Joshi, P.K. (Peter), Noordam, R. (Raymond), Marioni, R.E. (Riccardo), Hwang, S.-J. (Shih-Jen), Musani, S.K. (Solomon K.), Schminke, U. (Ulf), Palmas, W. (Walter), Isaacs, A.J. (Aaron), Correa, D.D., Zonderman, A.B., Hofman, A. (Albert), Teumer, A. (Alexander), Cox, A.J. (Amanda J.), Uitterlinden, A.G. (André), Wong, A. (Andrew), Smit, A.J. (Andries), Newman, A.B. (Anne B.), Britton, A.R., Ruusalepp, A. (Arno), Sennblad, B. (Bengt), Hedblad, B. (Bo), Pasaniuc, B. (Bogdan), Penninx, B.W.J.H. (Brenda), Langefeld, C.D. (Carl D.), Wassel, C.L. (Christina), Tzourio, C. (Christophe), Fava, C. (Cristiano), Baldassarre, D. (Damiano), O’Leary, D.H. (Daniel H.), Teupser, D. (Daniel), Kuh, D. (Diana), Tremoli, E. (Elena), Mannarino, E. (Elmo), Grossi, E. (Enzo), Boerwinkle, E.A. (Eric), Schadt, E.E. (Eric E.), Ingelsson, E. (Erik), Veglia, F. (Fabrizio), Rivadeneira Ramirez, F. (Fernando), Beutner, F. (Frank), Chauhan, G. (Ganesh), Heiss, G. (Gerardo), Snieder, H. (Harold), Campbell, H. (Harry), Völzke, H. (Henry), Markus, H.S. (Hugh), Deary, I.J. (Ian), Jukema, J.W. (Jan Wouter), Graaf, J. (Jacqueline) de, Price, J. (Jacqueline), Pott, J. (Janne), Hopewell, J., Liang, J. (Jingjing), Thiery, J.P. (Joachim), Engmann, J. (Jorgen), Gertow, K. (Karl), Rice, K.M. (Kenneth), Taylor, K.D. (Kent), Dhana, K. (Klodian), Kiemeney, L.A.L.M. (Lambertus A. L. M.), Kao, W.H.L. (Wen), Raffield, L.M. (Laura M.), Launer, L.J. (Lenore), Holdt, L.M. (Lesca), Dörr, M. (Marcus), Kubisch, C. (Christian), Traylor, M. (Matthew), Sitzer, M. (Matthias), Kumari, M. (Meena), Kivimaki, M. (Mika), Nalls, M.A. (Michael), Melander, O. (Olle), Raitakari, O. (Olli), Franco, O.H. (Oscar), Rueda-Ochoa, O.L. (Oscar), Roussos, A. (Alexandra), Whincup, P.H. (Peter), Amouyel, P. (Philippe), Giral, P. (Philippe), Anugu, P. (Pramod), Wong, Q. (Quenna), Malik, R. (Rainer), Rauramaa, R. (Rainer), Burkhardt, R. (Ralph), Hardy, R. (Rebecca), Schmidt, R. (Reinhold), Mutsert, R. (Reneé) de, Strawbridge, R.J. (Rona), Wannamethee, S.G. (Goya), Hägg, S. (Sara), Shah, S. (Sonia), McLachlan, S. (Stela), Trompet, S. (Stella), Seshadri, S. (Sudha), Kurl, S. (Sudhir), Heckbert, S.R. (Susan), Ring, S.M. (Susan), Harris, T.B. (Tamara B.), Lehtimäki, T. (Terho), Galesloot, T.E. (Tessel), Shah, T. (Tina), Faire, U. (Ulf) de, Plagnol, V. (Vincent), Rosamond, W.D. (Wayne), Post, W.S. (Wendy S.), Zhu, X. (Xiaofeng), Zhang, X. (Xiaoling), Guo, X. (Xiuqing), Saba, Y. (Yasaman), Okada, Y. (Yukinori), Mishra, A. (Aniket), Rutten-Jacobs, L. (Loes), Giese, A.-K. (Anne-Katrin), van der Laan, S.W. (Sander W.), Gretarsdottir, S. (Solveig), Anderson, C.D. (Christopher D.), Chong, M. (Michael), Adams, H.H.H. (Hieab), Ago, T. (Tetsuro), Almgren, P. (Peter), Ay, H. (Hakan), Bartz, T.M. (Traci M.), Benavente, O.R. (Oscar R.), Bevan, S. (Steve), Boncoraglio, G. (Giorgio Battista), Brown, R.D. (Robert D.), Butterworth, A.S. (Adam S.), Carrera, C. (Caty), Carty, C.L. (Cara L.), Chasman, D.I. (Daniel), Chen, W-M., Cole, J.W. (John W.), Cotlarciuc, I. (Ioana), Cruchaga, C. (Carlos), Danesh, J. (John), Bakker, P.I.W. (Paul) de, DeStefano, A.L. (Anita), Hoed, M. (Marcel) den, Duan, Q. (Qing), Engelter, S.T. (Stefan), Falcone, G.J. (Guido J.), Gottesman, R.F. (Rebecca), Grewal, R.P. (Raji P.), Gustafsson, S. (Stefan), Haessler, J. (Jeff), Harris, T.B. (Tamara), Hassan, A. (Ahamad), Havulinna, A.S. (Aki), Holliday, E.G. (Elizabeth), Howard, G. (George), Hsu, F.-C. (Fang-Chi), Hyacinth, H.I. (Hyacinth I.), Ikram, M.A. (Arfan), Irvin, M.R. (Marguerite R.), Jian, X. (Xueqiu), Jimenez-Conde, J. (Jordi), Johnson, J.A. (Julie A.), Jukema, J.W. (J. Wouter), Kanai, M. (Masahiro), Keene, K.L. (Keith), Kissela, B.M. (Brett M.), Kleindorfer, D.O. (Dawn O.), Kooperberg, C. (Charles), Kubo, M. (Michiaki), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Lee, J.-M. (Jin-Moo), Lemmens, R. (Robin), Leys, D. (Didier), Lewis, C.M. (Cathryn), Lin, W.-Y. (Wei-Yu), Lindgren, A.G. (Arne G.), Lorentzen, E. (Erik), Magnusson, P.K. (Patrik), Maguire, J.M. (Jane), Manichaikul, A. (Ani), McArdle, P.F. (Patrick), Meschia, J.F. (James F.), Mosley, T.H. (Thomas H.), Ninomiya, T. (Toshiharu), O’Donnell, M.J. (Martin J.), Pulit, S.L. (Sara), Rannikmäe, K. (Kristiina), Reiner, A.P. (Alexander P.), Rexrode, K. (Kathryn), Rich, S.S. (Stephen), Ridker, P.M. (Paul), Rost, N.S. (Natalia), Rothwell, P.M. (Peter), Rundek, T. (Tatjana), Muir, K.W. (Keith), Sakaue, S. (Saori), Sale, M.M. (Michele M.), Salomaa, V. (Veikko), Sapkota, B.R. (Bishwa R.), Schmidt, C.O. (Carsten O.), Sharma, P. (Pankaj), Slowik, A. (Agnieszka), Sudlow, C. (Cathie), Tanislav, C. (Christian), Tatlisumak, T. (Turgut), Thijs, V. (Vincent), Thorleifsson, G. (Gudmar), Thorsteinsdottir, U. (Unnur), Tiedt, S. (Steffen), Walters, M. (Matthew), Wareham, N.J. (Nick), Wassertheil-Smoller, S. (Sylvia), Wiggins, K.L. (Kerri), Yang, Q. (Qiong Fang), Yusuf, S. (Salim), Pastinen, T. (Tomi), Schadt, E.E. (Eric), Koplev, S. (Simon), Codoni, V. (Veronica), Civelek, M. (Mete), Smith, N.L. (Nicholas), Tregouet, D.-A. (David-Alexandre), Christophersen, I.E. (Ingrid E.), Roselli, C. (Carolina), Lubitz, S.A. (Steven A.), Ellinor, P.T. (Patrick), Tai, E.S. (E. Shyong), Kooner, J.S. (Jaspal S.), Kato, N. (Norihiro), He, J. (Jiang), Harst, P. (Pim) van der, Elliott, P. (Paul), Chambers, J.C. (John C.), Takeuchi, F. (Fumihiko), Johnson, A.D. (Andrew), Sanghera, D.K. (Dharambir K.), Jern, C. (Christina), Strbian, D. (Daniel), Fernandez-Cadenas, I. (Israel), Longstreth Jr, W.T., Rolfs, A. (Arndt), Hata, J. (Jun), Woo, D. (Daniel), Rosand, J. (Jonathan), Pare, G. (Guillame), Saleheen, D. (Danish), Zwart, J-A. (John-Anker), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Howson, J.M.M. (Joanna M. M.), Kamatani, Y. (Yoichiro), Dehghan, A. (Abbas), Seldenrijk, K.A. (Kees), Morrison, A.C. (Alanna), Hamsten, A. (Anders), Psaty, B.M. (Bruce), Duijn, C.M. (Cornelia) van, Lawlor, D.A. (Debbie), Mook-Kanamori, D.O. (Dennis O.), Bowden, D.W. (Donald), Schmidt, H. (Helena), Wilson, J.F. (James F.), Wilson, J.F. (James), Rotter, J.I. (Jerome I.), Wardlaw, J.M. (J.), Deanfield, J. (John), Halcox, J. (Julian), Lyytikäinen, L.-P. (Leo-Pekka), Loeffler, M. (Markus), Evans, M.K. (Michele), Debette, S. (Stéphanie), Humphries, S.E. (Steve), Völker, U. (Uwe), Gudnason, V. (Vilmundur), Hingorani, A. (Aroon), Björkegren, J.L.M. (Johan L.M.), Casas, J.P. (Juan), Ódonnell, C.J. (Christopher), and Morris, R.W. (Richard)
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
Published: 2018
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70. A DNA methylation biomarker of alcohol consumption

Author: Liu, C. (C.), Marioni, R.E. (Riccardo), Hedman, A.K. (Asa), Pfeiffer, L. (L.), Tsai, P.-C. (P. C.), Reynolds, L.M. (Lindsay), Just, A.C. (A. C.), Duan, Q. (Qing), Boer, C.G. (Cindy), Tanaka, T. (T.), Elks, C.E. (Cathy), Aslibekyan, S. (S.), Brody, J.A. (Jennifer A.), Kuhnel, B. (Brigitte), Herder, C. (Christian), Almli, L.M. (L. M.), Zhi, D. (D.), Wang, Y. (Y.), Huan, T. (T.), Yao, C. (C.), Mendelson, M.M. (M. M.), Joehanes, R. (Roby), Liang, L. (Liming), Love, S.-A. (S. A.), Guan, W. (Weihua), Shah, S. (S.), McRae, A.F. (A. F.), Kretschmer, A. (A.), Prokisch, H. (Holger), Strauch, K. (K.), Peters, A. (Annette), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Guo, X. (Xiuqing), Wiggins, K.L. (Kerri), Smith, A.K. (A. K.), Binder, E.B. (Elisabeth), Ressler, K.J. (Kerry), Irvin, M.R. (M. R.), Absher, D.M. (D. M.), Hernandez, D.G. (Dena), Ferrucci, L. (Luigi), Bandinelli, S. (Stefania), Lohman, K. (K.), Ding, J. (J.), Trevisi, L. (L.), Gustafsson, S. (Stefan), Sandling, J.K. (Johanna), Stolk, L. (Lisette), Uitterlinden, A.G. (André), Yet, I. (Idil), Castillo-Fernandez, J.E. (J. E.), Spector, T.D. (Timothy), Schwartz, J.D. (J. D.), Vokonas, P. (P.), Kao, W.H.L. (Wen), Li, Y. (Y.), Fornage, M. (Myriam), Arnett, D.K. (Donna), Wareham, N.J. (Nick), Sotoodehnia, N. (Nona), Ong, K.K. (Ken), Meurs, J.B.J. (Joyce) van, Conneely, K.N. (Karen N.), Baccarelli, A.A. (A. A.), Deary, I.J. (Ian), Bell, J.T. (J. T.), North, K.E. (Kari), Liu, Y. (YongMei), Waldenberger, M. (M.), London, S.J. (S. J.), Ingelsson, E. (Erik), Levy, D. (D.), Liu, C. (C.), Marioni, R.E. (Riccardo), Hedman, A.K. (Asa), Pfeiffer, L. (L.), Tsai, P.-C. (P. C.), Reynolds, L.M. (Lindsay), Just, A.C. (A. C.), Duan, Q. (Qing), Boer, C.G. (Cindy), Tanaka, T. (T.), Elks, C.E. (Cathy), Aslibekyan, S. (S.), Brody, J.A. (Jennifer A.), Kuhnel, B. (Brigitte), Herder, C. (Christian), Almli, L.M. (L. M.), Zhi, D. (D.), Wang, Y. (Y.), Huan, T. (T.), Yao, C. (C.), Mendelson, M.M. (M. M.), Joehanes, R. (Roby), Liang, L. (Liming), Love, S.-A. (S. A.), Guan, W. (Weihua), Shah, S. (S.), McRae, A.F. (A. F.), Kretschmer, A. (A.), Prokisch, H. (Holger), Strauch, K. (K.), Peters, A. (Annette), Visscher, P.M. (Peter), Wray, N.R. (Naomi), Guo, X. (Xiuqing), Wiggins, K.L. (Kerri), Smith, A.K. (A. K.), Binder, E.B. (Elisabeth), Ressler, K.J. (Kerry), Irvin, M.R. (M. R.), Absher, D.M. (D. M.), Hernandez, D.G. (Dena), Ferrucci, L. (Luigi), Bandinelli, S. (Stefania), Lohman, K. (K.), Ding, J. (J.), Trevisi, L. (L.), Gustafsson, S. (Stefan), Sandling, J.K. (Johanna), Stolk, L. (Lisette), Uitterlinden, A.G. (André), Yet, I. (Idil), Castillo-Fernandez, J.E. (J. E.), Spector, T.D. (Timothy), Schwartz, J.D. (J. D.), Vokonas, P. (P.), Kao, W.H.L. (Wen), Li, Y. (Y.), Fornage, M. (Myriam), Arnett, D.K. (Donna), Wareham, N.J. (Nick), Sotoodehnia, N. (Nona), Ong, K.K. (Ken), Meurs, J.B.J. (Joyce) van, Conneely, K.N. (Karen N.), Baccarelli, A.A. (A. A.), Deary, I.J. (Ian), Bell, J.T. (J. T.), North, K.E. (Kari), Liu, Y. (YongMei), Waldenberger, M. (M.), London, S.J. (S. J.), Ingelsson, E. (Erik), and Levy, D. (D.)
Abstract: The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal = 13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n = 6926) and identified 144 CpGs that provided substantial discrimination (area under the curve = 0.90-0.99) for current heavy alcohol intake (≥42 g per day in men and ≥28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1×10-7. Analysis of the monocyte-derived DNA (n = 1251) identified 62 alcohol-related CpGs at P<1×10-7. In whole-blood samples of people of European ancestry, we detected differen
Published: 2018
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71. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K i

Author: Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), Levy, D. (Daniel), Feitosa, M.F. (Mary Furlan), Kraja, A. (Aldi), Chasman, D.I. (Daniel), Sung, Y.J. (Yun J.), Winkler, T.W. (Thomas W.), Ntalla, I. (Ioanna), Guo, X. (Xiuqing), Franceschini, N. (Nora), Cheng, C.-Y. (Ching-Yu), Sim, X. (Xueling), Vojinović, D. (Dina), Marten, J. (Jonathan), Musani, S.K. (Solomon K.), Li, C. (Changwei), Bentley, A.R. (Amy), Brown, M.R., Schwander, K., Richard, M.A. (Melissa A.), Noordam, R. (Raymond), Aschard, H. (Hugues), Bartz, T.M. (Traci M.), Bielak, L.F. (Lawrence F.), Dorajoo, R. (Rajkumar), Fisher, V. (Virginia), Hartwig, F.P. (Fernando P.), Horimoto, A.R.V.R. (Andrea R. V.R.), Lohman, K.K. (Kurt K.), Manning, A.K. (Alisa), Rankinen, T. (Tuomo), Smith, A.V. (Albert), Tajuddin, S.M. (Salman M.), Wojczynski, M.K. (Mary ), Alver, M. (Maris), Boissel, M. (Mathilde), Cai, Q. (Qiuyin), Campbell, A. (Archie), Chai, J.F. (Jin Fang), Chen, X. (Xu), Divers, J. (Jasmin), Gao, C. (Chuan), Goel, A. (Anuj), Hagemeijer, Y. (Yanick), Harris, S.E. (Sarah), He, M. (Meian), Hsu, F.-C. (Fang-Chi), Jackson, A.U. (Anne), Kähönen, M. (Mika), Kasturiratne, A. (Anuradhani), Komulainen, P. (Pirjo), Kuhnel, B. (Brigitte), Laguzzi, F. (Federica), Luan, J., Matoba, N. (Nana), Nolte, I.M. (Ilja), Padmanabhan, S. (Sandosh), Riaz, M. (Muhammad), Rueedi, R. (Rico), Robino, A. (Antonietta), Said, M.A. (M. Abdullah), Scott, R.A. (Robert), Sofer, T. (Tamar), Stancáková, A. (Alena), Takeuchi, F. (Fumihiko), Tayo, B. (Bamidele), Most, P.J. (Peter) van der, Varga, T.V. (Tibor V.), Vitart, V. (Veronique), Wang, Y. (Yajuan), Ware, E.B. (Erin B.), Warren, H. (Helen), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Afaq, S. (Saima), Amin, N. (Najaf), Amini, M. (Marzyeh), Arking, D.E. (Dan), Aung, T. (Tin), Boerwinkle, E. (Eric), Borecki, I.B. (Ingrid), Broeckel, U. (Ulrich), Brown, M. (Morris), Brumat, M. (Marco), Burke, G.L. (Greg), Canouil, M. (Mickaël), Chakravarti, A. (Aravinda), Charumathi, S. (Sabanayagam), Chen, Y.D.I. (Yii-Der Ida), Connell, J.M. (John M.), Correa, D.D., De Las Fuentes, L. (Lisa), Mutsert, R. (Reneé) de, De Silva, H.J. (H. Janaka), Deng, X. (Xuan), Ding, J. (Jingzhong), Duan, Q. (Qing), Eaton, C.B. (Charles B.), Ehret, G. (Georg), Eppinga, R.N. (Ruben N.), Evangelou, E. (Evangelos), Faul, J.D. (Jessica D.), Felix, S.B. (Stephan B.), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Friedlander, Y. (Yechiel), Gandin, I. (Ilaria), Gao, H. (He), Ghanbari, M. (Mohsen), Gigante, B. (Bruna), Gu, C. (Charles), Gu, D. (Dongfeng), Hagenaars, S. (Saskia), Hallmans, G. (Göran), Harris, T.B. (Tamara), He, J. (Jiang), Heikkinen, S. (Sami), Heng, C.K. (Chew-Kiat), Hirata, M. (Makoto), Howard, B.V. (Barbara V.), Ikram, M.K. (Kamran), John, U. (Ulrich), Katsuya, T. (Tomohiro), Khor, C.C., Kilpeläinen, T.O. (Tuomas), Koh, W.-P. (Woon-Puay), Krieger, J.E. (José), Kritchevsky, S.B. (Stephen), Kubo, M. (Michiaki), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lewis, C.E. (Cora E.), Li, Y. (Yize), Lin, S. (Shiow), Liu, J. (Jianjun), Liu, J. (Jingmin), Loh, M. (Marie), Louie, T. (Tin), Mägi, R. (Reedik), McKenzie, C.A. (Colin), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Milani, L. (Lili), Mohlke, K.L. (Karen), Momozawa, Y. (Yukihide), Nalls, M.A. (Michael), Nelson, C.P. (Christopher P.), Sotoodehnia, N. (Nona), Norris, J.M. (Jill M.), O´Connell, J.R., Palmer, N.D. (Nicholette), Perls, T.T. (Thomas T.), Pedersen, N.L. (Nancy), Peters, A. (Annette), Peyser, P.A. (Patricia A.), Poulter, N.R. (Neil), Raffel, L.J. (Leslie J.), Raitakari, O. (Olli), Roll, K. (Kathryn), Rose, L.M. (Lynda M.), Rosendaal, F.R. (Frits), Rotter, J.I. (Jerome I.), Schmidt, C.O. (Carsten Oliver), Schreiner, P.J. (Pamela), Schupf, N. (Nicole), Scott, W.R. (William R.), Sever, P. (Peter), Shi, Y. (Yuan), Sidney, S. (Stephen), Sims, M. (Mario), Sitlani, C.M. (Colleen), Smith, J.A. (Jennifer A), Snieder, H. (Harold), Starr, J.M. (John), Strauch, K. (Konstantin), Stringham, H.M. (Heather M.), Tan, N.Y.Q. (Nicholas Y.Q.), Tang, H. (Hua), Taylor, K.D. (Kent), Teo, Y.Y. (Yik Ying), Tham, Y.C. (Yih Chung), Turner, S.T. (Stephen T.), Uitterlinden, A.G. (André), Vollenweider, P. (Peter), Waldenberger, M. (Melanie), Wang, L. (Lihua), Wang, Y.X. (Ya Xing), Wei, W.B. (Wen Bin), Williams, C. (Christine), Yao, J. (Jie), Yu, C. (Caizheng), Yuan, J.-M. (Jian-Min), Zhao, W. (Wei), Zonderman, A.B., Becker, D.M. (Diane), Boehnke, M. (Michael), Bowden, D.W. (Donald W.), Chambers, J.C. (John C.), Deary, I.J. (Ian), Esko, T. (Tõnu), Farrall, M. (Martin), Franks, P.W. (Paul W.), Freedman, B.I. (Barry), Froguel, P. (Philippe), Gasparini, P. (Paolo), Gieger, C. (Christian), Jonas, J.B. (Jost Bruno), Kamatani, Y. (Yoichiro), Kato, N. (Norihiro), Kooner, J.S. (Jaspal S.), Kutalik, Z. (Zoltán), Laakso, M. (Markku), Laurie, C.C. (Cathy C.), Leander, K. (Karin), Lehtimäki, T. (Terho), Magnusson, P.K. (Patrik), Oldehinkel, A.J. (Albertine), Penninx, B.W.J.H. (Brenda), Polasek, O. (Ozren), Porteous, D.J. (David J.), Rauramaa, R. (Rainer), Samani, N.J. (Nilesh J.), Scott, J. (James), Shu, X.-O. (Xiao-Ou), Van Der Harst, P. (Pim), Wagenknecht, L.E. (Lynne), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weir, D.R. (David R.), Wickremasinghe, A.R. (Ananda), Wu, T. (Tangchun), Zheng, W. (Wei), Bouchard, C. (Claude), Christensen, K. (Kaare), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Horta, B.L. (Bernardo L.), Kardia, S.L.R. (Sharon L.R.), Liu, Y. (YongMei), Pereira, A.C. (Alexandre C.), Psaty, B.M. (Bruce M.), Ridker, P.M. (Paul), Dam, R.M. (Rob) van, Gauderman, W.J. (W James), Zhu, X. (Xiaofeng), Mook-Kanamori, D.O. (Dennis O.), Fornage, M. (Myriam), Rotimi, C. (Charles), Cupples, L.A. (Adrienne), Kelly, T.N. (Tanika N.), Fox, E.R. (Ervin), Hayward, C. (Caroline), Duijn, C.M. (Cornelia) van, Tai, E.S. (E. Shyong), Wong, T.Y. (Tien Yin), Kooperberg, C. (Charles), Palmas, W. (Walter), Rice, K.M. (Kenneth), Morrison, A.C. (Alanna), Elliott, P. (Paul), Caulfield, M. (Mark), Munroe, P. (Patricia), Rao, D.C. (Dabeeru C.), Province, M.A. (Mike), and Levy, D. (Daniel)
Abstract: Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in ≈131K individuals across several ancestry groups yielded 3, 514 SNVs (245 loci) with suggestive evidence of association (P < 1.0 × 10-5). In Stage 2, these SNVs were tested for independent external replication in ≈440K individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2, 159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 × 10-8). For African ancestry samples, we detected 18 potentially novel BP loci (P < 5.0 × 10-8) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2) have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
Published: 2018
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72. Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels

Author: Jiang, X. (Xia), O'Reilly, P.F. (Paul), Aschard, H. (Hugues), Hsu, Y.-H. (Yi-Hsiang), Richards, J.B. (J. Brent), Dupuis, J. (Josée), Ingelsson, E. (Erik), Karasik, D. (David), Pilz, D.T. (Daniela), Berry, D. (Diane), Kestenbaum, B. (Bryan), Zheng, J. (Jusheng), Luan, J. (Jianan), Sofianopoulou, E. (Eleni), Streeten, E.A. (Elizabeth), Albanes, D. (Demetrius), Lutsey, P.L. (Pamela), Yao, L. (Lu), Tang, W. (Weihong), Econs, M.J. (Michael), Wallaschofski, H. (Henri), Völzke, H. (Henry), Zhou, A. (Ang), Power, C. (Christopher), McCarthy, M.I. (Mark I.), Michos, E.D. (Erin D.), Boerwinkle, E. (Eric), Weinstein, S.J. (Stephanie J.), Freedman, N.D. (Neal D.), Huang, W.-Y. (Wen-Yi), Schoor, N.M. (Natasja) van, Velde, N. (Nathalie) van der, Groot, L.C.P.G.M.D. (Lisette C.P.G.M. De), Enneman, A.W. (Anke), Cupples, L.A. (Adrienne), Booth, S.L. (Sarah L.), Vasan, R. (Ramachandran), Liu, C.-T. (Ching-Ti), Zhou, Y. (Yanhua), Ripatti, S. (Samuli), Ohlsson, C. (Claes), Vandenput, L. (Liesbeth), Lorentzon, M. (Mattias), Hagen, K. (Knut), Shea, M.K. (M. Kyla), Houston, D.K. (Denise K.), Kritchevsky, S.B. (Stephen B.), Liu, Y. (YongMei), Lohman, K.K. (Kurt K.), Ferrucci, L. (Luigi), Peacock, M. (Munro), Gieger, C. (Christian), Beekman, M. (Marian), Slagboom, P.E. (Eline), Deelen, J. (Joris), Heemst, D.V. (DIana Van), Kleber, M.E. (Marcus), März, W. (Winfried), Boer, I.H. (Ian) de, Wood, A.C. (Alexis C.), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Robinson-Cohen, C. (Cassianne), Heijer, M. (Martin) den, Jarvelin, M.-R. (Marjo-Riitta), Cavadino, A. (Alana), Joshi, P.K. (Peter), Wilson, J.F. (James F.), Hayward, C. (Caroline), Kao, W.H.L. (Wen), Michaëlsson, K. (Karl), Trompet, S. (Stella), Zillikens, M.C. (Carola), Uitterlinden, A.G. (Andre G.), Rivadeneira Ramirez, F. (Fernando), Broer, L. (Linda), Zgaga, L. (Lina), Campbell, H. (Harry), Theodoratou, E. (Evropi), Farrington, S.M. (Susan M.), Timofeeva, M.N. (Maria N.), Dunlop, M.G. (Malcolm), Valdes, A.M., Tikkanen, E. (Emmi), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Raitakari, O.T. (Olli T.), Mikkilä, V. (Vera), Ikram, M.A. (Arfan), Sattar, N. (Naveed), Jukema, J.W. (J. Wouter), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Forouhi, N.G. (Nita), Gundersen, T.E. (Thomas E.), Khaw, K.-T. (Kay-Tee), Butterworth, A.S. (Adam S.), Danesh, J. (John), Spector, T.D. (Timothy), Wang, T.J. (Thomas J.), Hypponen, E. (Elina), Kraft, P. (Peter), Kiel, D.P. (Douglas P.), Jiang, X. (Xia), O'Reilly, P.F. (Paul), Aschard, H. (Hugues), Hsu, Y.-H. (Yi-Hsiang), Richards, J.B. (J. Brent), Dupuis, J. (Josée), Ingelsson, E. (Erik), Karasik, D. (David), Pilz, D.T. (Daniela), Berry, D. (Diane), Kestenbaum, B. (Bryan), Zheng, J. (Jusheng), Luan, J. (Jianan), Sofianopoulou, E. (Eleni), Streeten, E.A. (Elizabeth), Albanes, D. (Demetrius), Lutsey, P.L. (Pamela), Yao, L. (Lu), Tang, W. (Weihong), Econs, M.J. (Michael), Wallaschofski, H. (Henri), Völzke, H. (Henry), Zhou, A. (Ang), Power, C. (Christopher), McCarthy, M.I. (Mark I.), Michos, E.D. (Erin D.), Boerwinkle, E. (Eric), Weinstein, S.J. (Stephanie J.), Freedman, N.D. (Neal D.), Huang, W.-Y. (Wen-Yi), Schoor, N.M. (Natasja) van, Velde, N. (Nathalie) van der, Groot, L.C.P.G.M.D. (Lisette C.P.G.M. De), Enneman, A.W. (Anke), Cupples, L.A. (Adrienne), Booth, S.L. (Sarah L.), Vasan, R. (Ramachandran), Liu, C.-T. (Ching-Ti), Zhou, Y. (Yanhua), Ripatti, S. (Samuli), Ohlsson, C. (Claes), Vandenput, L. (Liesbeth), Lorentzon, M. (Mattias), Hagen, K. (Knut), Shea, M.K. (M. Kyla), Houston, D.K. (Denise K.), Kritchevsky, S.B. (Stephen B.), Liu, Y. (YongMei), Lohman, K.K. (Kurt K.), Ferrucci, L. (Luigi), Peacock, M. (Munro), Gieger, C. (Christian), Beekman, M. (Marian), Slagboom, P.E. (Eline), Deelen, J. (Joris), Heemst, D.V. (DIana Van), Kleber, M.E. (Marcus), März, W. (Winfried), Boer, I.H. (Ian) de, Wood, A.C. (Alexis C.), Rotter, J.I. (Jerome I.), Rich, S.S. (Stephen), Robinson-Cohen, C. (Cassianne), Heijer, M. (Martin) den, Jarvelin, M.-R. (Marjo-Riitta), Cavadino, A. (Alana), Joshi, P.K. (Peter), Wilson, J.F. (James F.), Hayward, C. (Caroline), Kao, W.H.L. (Wen), Michaëlsson, K. (Karl), Trompet, S. (Stella), Zillikens, M.C. (Carola), Uitterlinden, A.G. (Andre G.), Rivadeneira Ramirez, F. (Fernando), Broer, L. (Linda), Zgaga, L. (Lina), Campbell, H. (Harry), Theodoratou, E. (Evropi), Farrington, S.M. (Susan M.), Timofeeva, M.N. (Maria N.), Dunlop, M.G. (Malcolm), Valdes, A.M., Tikkanen, E. (Emmi), Lehtimäki, T. (Terho), Lyytikäinen, L.-P. (Leo-Pekka), Kähönen, M. (Mika), Raitakari, O.T. (Olli T.), Mikkilä, V. (Vera), Ikram, M.A. (Arfan), Sattar, N. (Naveed), Jukema, J.W. (J. Wouter), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Forouhi, N.G. (Nita), Gundersen, T.E. (Thomas E.), Khaw, K.-T. (Kay-Tee), Butterworth, A.S. (Adam S.), Danesh, J. (John), Spector, T.D. (Timothy), Wang, T.J. (Thomas J.), Hypponen, E. (Elina), Kraft, P. (Peter), and Kiel, D.P. (Douglas P.)
Abstract: Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.
Published: 2018
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73. Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation

Author: Strawbridge, R.J., Silveira, A., Hoed, M. den, Gustafsson, S., Luan, J.A., Rybin, D., Dupuis, J., Li-Gao, R.F., Kavousi, M., Dehghan, A., Haljas, K., Lahti, J., Gadin, J.R., Backlund, A., Faire, U. de, Gertow, K., Giral, P., Goel, A., Humphries, S.E., Kurl, S., Langenberg, C., Lannfelt, L.L., Lind, L., Lindgren, C.C.M., Mannarino, E., Mook-Kanamori, D.O., Morris, A.P., Mutsert, R. de, Rauramaa, R., Saliba-Gustafsson, P., Sennblad, B., Smit, A.J., Syvanen, A.C., Tremoli, E., Veglia, F., Zethelius, B., Bjorck, H.M., Eriksson, J.G., Hofman, A., Franco, O.H., Watkins, H., Jukema, J.W., Florez, J.C., Wareham, N.J., Meigs, J.B., Ingelsson, E., Baldassarre, D., Hamsten, A., IMPROVE Study Grp, Medicum, Department of Psychology and Logopedics, University of Helsinki, Clinicum, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Developmental Psychology Research Group, Luan, Jian'an [0000-0003-3137-6337], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Carotid Artery Diseases, Male, EXPRESSION, endocrine system, Genetic variants, endocrine system diseases, Quantitative Trait Loci, PATHOPHYSIOLOGY, DEPENDENT DIABETES-MELLITUS, Vascular Remodeling, Carotid Intima-Media Thickness, Polymorphism, Single Nucleotide, INTIMA-MEDIA THICKNESS, Gene Frequency, Risk Factors, Intima-media-thickness, Humans, Genetic Predisposition to Disease, CORONARY-HEART-DISEASE, COHORT, cardiovascular diseases, Mendelian randomisation, EUROPEAN POPULATION, COMMON, Genetic Association Studies, Chromosomes, Human, Pair 15, MEN, Single nucleotide polymorphisms, Mendelian Randomization Analysis, Atherosclerosis, INSULIN, Europe, Phenotype, 3121 General medicine, internal medicine and other clinical medicine, Asymptomatic Diseases, Linear Models, Female, hormones, hormone substitutes, and hormone antagonists, Proinsulin
Abstract: Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling. Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants. Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures. Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.
Published: 2017

74. Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease

Author: Webb, T.R., Erdmann, J., Stirrups, K.E., Stitziel, N.O., Masca, N.G.D., Jansen, H., Kanoni, S., Nelson, C.P., Ferrario, P.G., Konig, I.R., Eicher, J.D., Johnson, A.D., Hamby, S.E., Betsholtz, C., Ruusalepp, A., Franzen, O., Schadt, E.E., Bjorkegren, J.L.M., Weeke, P.E., Auer, P.L., Schick, U.M., Lu, Y.C., Zhang, H., Dube, M.P., Goel, A., Farrall, M., Peloso, G.M., Won, H.H., R. do, Iperen, E. van, Kruppa, J., Mahajan, A., Scott, R.A., Willenborg, C., Braund, P.S., Capelleveen, J.C. van, Doney, A.S.F., Donnelly, L.A., Asselta, R., Merlini, P.A., Duga, S., Marziliano, N., Denny, J.C., Shaffer, C., El-Mokhtari, N.E., Franke, A., Heilmann, S., Hengstenberg, C., Hoffmann, P., Holmen, O.L., Hveem, K., Jansson, J.H., Jockel, K.H., Kessler, T., Kriebel, J., Laugwitz, K.L., Marouli, E., Martinelli, N., McCarthy, M.I., Zuydam, N.R. van, Meisinger, C., Esko, T., Mihailov, E., Escher, S.A., Alver, M., Moebus, S., Morris, A.D., Virtamo, J., Nikpay, M., Olivieri, O., Provost, S., AlQarawi, A., Robertson, N.R., Akinsansya, K.O., Reilly, D.F., Vogt, T.F., Yin, W., Asselbergs, F.W., Kooperberg, C., Jackson, R.D., Stahl, E., Muller-Nurasyid, M., Strauch, K., Varga, T.V., Waldenberger, M., Zeng, L.Y., Chowdhury, R., Salomaa, V., Ford, I., Jukema, J.W., Amouyel, P., Kontto, J., Nordestgaard, B.G., Ferrieres, J., Saleheen, D., Sattar, N., Surendran, P., Wagner, A., Young, R., Howson, J.M.M., Butterworth, A.S., Danesh, J., Ardissino, D., Bottinger, E.P., Erbel, R., Franks, P.W., Girelli, D., Hall, A.S., Hovingh, G.K., Kastrati, A., Lieb, W., Meitinger, T., Kraus, W.E., Shah, S.H., McPherson, R., Orho-Melander, M., Melander, O., Metspalu, A., Palmer, C.N.A., Peters, A., Rader, D.J., Reilly, M.P., Loos, R.J.F., Reiner, A.P., Roden, D.M., Tardif, J.C., Thompson, J.R., Wareham, N.J., Watkins, H., Willer, C.J., Samani, N.J., Schunkert, H., Deloukas, P., Kathiresan, S., Wellcome Trust Case Control, MORGAM Investigators, and Myocardial Infarction Genetics
Subjects: expression quantitative trait loci, single nucleotide polymorphism, cholesteryl ester transfer protein, genome-wide association, genetics
Abstract: BACKGROUND: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits. OBJECTIVES: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci. METHODS: In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs. RESULTS: We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 × 10(-4) with a range of other diseases/traits. CONCLUSIONS: We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
Published: 2017

75. Consumption of fish is not associated with risk of differentiated thyroid carcinoma in the European prospective investigation into cancer and nutrition (EPIC) study

Author: Zamora-Ros, R. Castañeda, J. Rinaldi, S. Cayssials, V. Slimani, N. Weiderpass, E. Tsilidis, K.K. Boutron-Ruault, M.-C. Overvad, K. Eriksen, A.K. Tjønneland, A. Kühn, T. Katzke, V. Boeing, H. Trichopoulou, A. La Vecchia, C. Kotanidou, A. Palli, D. Grioni, S. Mattiello, A. Tumino, R. Sciannameo, V. Lund, E. Merino, S. Salamanca-Fernández, E. Amiano, P. Huerta, J.M. Barricarte, A. Ericson, U. Almquist, M. Hennings, J. Sandström, M. Bueno-de-Mesquita, H.B. Peeters, P.H. Khaw, K.-T. Wareham, N.J. Schmidt, J.A. Cross, A.J. Riboli, E. Scalbert, A. Romieu, I. Agudo, A. Franceschi, S.
Abstract: Background: Differentiated thyroid cancer (TC) is the most common endocrine cancer. Fish can be an important source of iodine and other micronutrients and contaminants that may affect the thyroid gland and TC risk. Objective: We prospectively evaluated the relations between the consumption of total fish and different fish types and shellfish and TC risk in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Methods: EPIC is a cohort of > 500,000 men and women, mostly aged 35-70 y, who were recruited in 10 European countries. After a mean follow-up of 14 y, 748 primary differentiated TC cases were diagnosed; 666 were in women and 601 were papillary TC. Data on intakes of lean fish, fatty fish, fish products, and shellfish were collected by using countryspecific validated dietary questionnaires at recruitment. Multivariable Cox regression was used to calculate HRs and 95% CIs adjusted for many potential confounders, including dietary and nondietary factors. Results: No significant association was observed between total fish consumption and differentiated TC risk for the highest compared with the lowest quartile (HR: 1.03; 95% CI: 0.81, 1.32; P-trend = 0.67). Likewise, no significant association was observed with the intake of any specific type of fish, fish product, or shellfish. No significant heterogeneity was found by TC subtype (papillary or follicular tumors), by sex, or between countries with low and high TC incidence. Conclusion: This large study shows that the intake of fish and shellfish was not associated with differentiated TC risk in Europe, a region in which iodine deficiency or excess is rare. © 2017 American Society for Nutrition.
Published: 2017

76. New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475,000 Individuals

Author: Chasman, D.I., Herzig, K.-H., Laakso, M., Kraja, A.T., Padmanabhan, S., Amin, N., Marioni, R.E., Giulianini, F., Havulinna, A.S., Asselbergs, F.W., Stafford, J.M., Stirrups, K.E., Fornage, M., Danesh, J., Lindgren, C.M., Bonnycastle, L.L., Zhang, H., Groop, L., Loos, R.J.F., J��rgensen, M.E., Christensen, C.K., CHD Exome+, Rudan, I., Butterworth, A.S., Cook, J.P., Liu, Y., Morrison, A.C., Guo, X., Barnes, M.R., Fava, C., Province, M.A., K��r��j��m��ki, A., Wareham, N.J., Deary, I.J., CHARGE EXOME BP, Edwards, T.L., Poveda, A., Kooperberg, C., Have, C.T., Ingelsson, E., Wain, L.V., Rotter, J.I., Levy, D., Tragante, V., Young, R., Cabrera, C.P., Connell, J.M., Caulfield, M.J., Little, L., Jarvelin, M.-R., Warren, H.R., Zhang, W., Rayner, N.W., Gambaro, G., Munroe, P.B., Ferreira, T., Morris, A.P., Farmaki, A.-E., Smith, A.V., Pedersen, O., Esko, T., Heikki, O., Bork-Jensen, J., Witte, D.R., Drenos, F., Southam, L., Deloukas, P., Franceschini, N., Zeggini, E., Lind, L., Van Der Harst, P., Riaz, M., Rice, K., Grarup, N., Dominiczak, A.F., Vergnaud, A.-C., Hayward, C., Ehret, G.B., Melander, O., Tzoulaki, I., Boerwinkle, E., Evangelou, E., Wilson, J.G., Polasek, O., Harris, S.E., Tuomilehto, J., Franks, P.W., McCarthy, M.I., Skaaby, T., D��rr, M., Poulter, N.R., Salomaa, V., Finland, Willer, C.J., Saleheen, D., The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group, Lakka, T.A., Newton-Cheh, C., Kooner, J.S., Exome BP, Samani, N.J., Van Der Meer, P., Kardia, S.L.R., Gao, H., Mei, H., Surendran, P., Van Duijn, C.M., Richard, M.A., Gudnason, V., Smith, J.A., Boehnke, M., Varga, T.V., Hansen, T., M��gi, R., Chambers, J.C., Mahajan, A., Rauramaa, R., Tuomi, T., Yiorkas, A.M., Psaty, B.M., Dedoussis, G., Brandslund, I., Sever, P.J., Mohlke, K.L., Weiss, S., Liu, C., Langenberg, C., De Boer, R.A., Blakemore, A.I.F., Grove, M.L., Malerba, G., Karpe, F., Lu, Y., Joehanes, R., Stan��kov��, A., Manning, A.K., Sim, X., Ridker, P.M., Starr, J.M., Hallmans, G., Elliott, P., Howson, J.M.M., GoT2D:T2DGenes Consortia, Palmer, C.N.A., Linneberg, A., Palmas, W., Menni, C., and Giri, A.
Abstract: Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. Methods and Results - Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ��475 000), and the other in the subset of individuals of European descent (��423 000). Twenty-one SNVs were genome-wide significant (P
Published: 2017
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77. Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity

Author: Hendricks, A.E. Bochukova, E.G. Marenne, G. Keogh, J.M. Atanassova, N. Bounds, R. Wheeler, E. Mistry, V. Henning, E. Körner, A. Muddyman, D. McCarthy, S. Hinney, A. Hebebrand, J. Scott, R.A. Langenberg, C. Wareham, N.J. Surendran, P. Howson, J.M. Butterworth, A.S. Danesh, J. Nordestgaard, Bø.G. Nielsen, S.F. Afzal, S. Papadia, S. Ashford, S. Garg, S. Millhauser, G.L. Palomino, R.I. Kwasniewska, A. Tachmazidou, I. O'Rahilly, S. Zeggini, E. Barroso, I. Farooqi, I.S. Benzeval, M. Burton, J. Buck, N. Jäckle, A. Kumari, M. Laurie, H. Lynn, P. Pudney, S. Rabe, B. Wolke, D. Overvad, K. Tjønneland, A. Clavel-Chapelon, F. Kaaks, R. Boeing, H. Trichopoulou, A. Ferrari, P. Palli, D. Krogha, V. Panico, S. Tuminoa, R. Matullo, G. Boer, J. Van Der Schouw, Y. Weiderpass, E. Quiros, J.R. Sánchez, M.-J. Navarro, C. Moreno-Iribas, C. Arriola, L. Melander, O. Wennberg, P. Key, T.J. Riboli, E. Turki, S.A. Anderson, C.A. Anney, R. Antony, D. Soler Artigas, M. Ayub, M. Bala, S. Barrett, J.C. Beales, P. Bentham, J. Bhattacharyaa, S. Birney, E. Blackwooda, D. Bobrow, M. Bolton, P.F. Boustred, C. Breen, G. Calissanoa, M. Carss, K. Charlton, R. Chatterjee, K. Chen, L. Ciampia, A. Cirak, S. Clapham, P. Clement, G. Coates, G. Coccaa, M. Collier, D.A. Cosgrove, C. Coxa, T. Craddock, N. Crooks, L. Curran, S. Curtis, D. Daly, A. Danecek, P. Day, I.N.M. Day-Williams, A. Dominiczak, A. Down, T. Du, Y. Dunham, I. Durbin, R. Edkins, S. Ekong, R. Ellis, P. Evansa, D.M. Fitzpatrick, D.R. Flicek, P. Floyd, J. Foley, A.R. Franklin, C.S. Futema, M. Gallagher, L. Gaunt, T.R. Geihs, M. Geschwind, D. Greenwood, C.M.T. Griffin, H. Grozeva, D. Guo, X. Guo, X. Gurling, H. Hart, D. Holmans, P. Howie, B. Huang, J. Huang, L. Hubbard, T. Humphries, S.E. Hurles, M.E. Hysi, P. Iotchkova, V. Jackson, D.K. Jamshidi, Y. Joyce, C. Karczewski, K.J. Kaye, J. Keane, T. Kemp, J.P. Kennedy, K. Kent, A. Khawaja, F. Van Kogelenberg, M. Kolb-Kokocinski, A. Lachance, G. Langford, C. Lawson, D. Lee, I. Lek, M. Li, R. Li, Y. Liang, J. Lin, H. Liu, R. Lönnqvist, J. Lopes, L.R. Lopes, M. MacArthur, D.G. Mangino, M. Marchini, J. Maslen, J. Mathieson, I. McGuffin, P. McIntosh, A.M. McKechanie, A.G. McQuillin, A. Memari, Y. Metrustry, S. Migone, N. Min, J.L. Mitchison, H.M. Moayyeri, A. Morris, A. Morris, J. Muntoni, F. Northstone, K. O'Donovan, M.C. Onoufriadis, A. Oualkacha, K. Owen, M.J. Palotie, A. Panoutsopoulou, K. Parker, V. Parr, J.R. Paternoster, L. Paunio, T. Payne, F. Payne, S.J. Perry, J.R.B. Pietilainen, O. Plagnol, V. Pollitt, R.C. Porteous, D.J. Povey, S. Quail, M.A. Quaye, L. Raymond, F.L. Rehnström, K. Richards, J.B. Ridout, C.K. Ring, S. Ritchie, G.R.S. Roberts, N. Robinson, R.L. Savage, D.B. Scambler, P. Schiffels, S. Schmidts, M. Schoenmakers, N. Scott, R.H. Semple, R.K. Serra, E. Sharp, S.I. Shaw, A. Shihab, H.A. Shin, S.-Y. Skuse, D. Small, K.S. Smee, C. Smith, B.H. Davey Smith, G. Soranzo, N. Southam, L. Spasic-Boskovic, O. Spector, T.D. St Clair, D. St Pourcain, B. Stalker, J. Stevens, E. Sun, J. Surdulescu, G. Suvisaari, J. Syrris, P. Taylor, R. Tian, J. Timpson, N.J. Tobin, M.D. Valdes, A.M. Vandersteen, A.M. Vijayarangakannan, P. Visscher, P.M. Wain, L.V. Walter, K. Walters, J.T.R. Wang, G. Wang, J. Wang, Y. Ward, K. Whyte, T. Williams, H.J. Williamson, K.A. Wilson, C. Wilson, S.G. Wong, K. Xu, C. Yang, J. Zhang, F. Zhang, P. Zheng, H.-F.
Abstract: Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and ANGPTL6. The p.S284X variant in ANGPTL6 drives the association signal (rs201622589, MAF∼0.1%, odds ratio = 10.13, p-value = 0.042) and results in complete loss of secretion in cells. Further analysis including additional case-control studies and population controls (N = 260,642) did not support association of this variant with obesity (odds ratio = 2.34, p-value = 2.59 × 10-3), highlighting the challenges of testing rare variant associations and the need for very large sample sizes. Further validation in cohorts with severe obesity and engineering the variants in model organisms will be needed to explore whether human variants in ANGPTL6 and other genes that lead to obesity when deleted in mice, do contribute to obesity. Such studies may yield druggable targets for weight loss therapies. © 2017 The Author(s).
Published: 2017

78. A common apolipoprotein B signal peptide polymorphism modifies the relation between plasma non-esterified fatty acids and triglyceride concentration in men

Author: Halsall, D.J, Martensz, N.D, Luan, J, Maison, P, Wareham, N.J, Hales, C.N, and Byrne, C.D
Published: 2000
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79. Metabolomic patterns associated with known genetic variants for hepatic steatosis and non-alcoholic steatohepatitisidentify biomarkers that may be of utility in predicting adverse liver outcomes

Author: Mann, J., primary, Allison, M., additional, Wittemans, L., additional, Rolfe, E.D.L., additional, Imamura, F., additional, Forouhi, N., additional, Lotta, L.A., additional, Griffin, J.L., additional, Koulman, A., additional, Langenberg, C., additional, and Wareham, N.J., additional
Published: 2018
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80. PS18 - 86. Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals

Author: van Vliet-Ostaptchouk, J.V., den Hoed, M., Luan, J., Zhao, J-H., Ong, K.K., van der Most, P.J., Wong, A., Hardy, R., Kuh, D., van der Klauw, M.M., Bruinenberg, M., Wolffenbuttel, B.H.R., Wareham, N.J., Snieder, H., and Loos, R.J.F.
Published: 2012
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81. Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

Author: Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), Montgomery, G.W. (G. W.), Hinney, A. (Anke), Kesselmeier, M. (M.), Jall, S. (S.), Volckmar, A.-L. (A. L.), Föcker, M. (M.), Antel, J. (J.), Heid, I.M. (Iris), Winkler, T.W. (Thomas W.), Grant, S.F.A. (S. F.A.), Guo, Y. (Yongli), Bergen, A.W. (Andrew), Grant, S.F.A. (Struan), Berrettini, W. (Wade), Hakonarson, H. (Hakon), Herpertz-Dahlmann, B. (B.), De Zwaan, M. (M.), Herzog, W. (W.), Ehrlich, S.M. (Stefan), Zipfel, S. (S.), Egberts, K. (Karin), Adan, R. (R.), Brandys, M. (M.), Elburg, A.A. (Annemarie) van, Boraska Perica, V. (V.), Müller, T.D., Tschöp, M.H. (M. H.), Zeggini, E. (Eleftheria), Bulik, C.M. (C. M.), Collier, D.A. (David), Scherag, A. (A.), Hebebrand, J. (J.), Tschop, M. (Matthias), Floyd, J. (Jamie), Thornton, L.M. (Laura), Huckins, L.M. (Laura M), Southam, L. (Lorraine), Rayner, N.W. (Nigel William), Tachmazidou, I. (Ioanna), Klump, K.L. (K. L.), Treasure, J. (Janet), Lewis, C.M. (Cathryn), Schmidt, U. (Ulrike), Tozzi, F. (Federica), Iezebrink, K. (Kirsty), Gorwood, P. (Philip), Kas, M.J.H. (Martien), Favaro, A. (Angela), Santonastaso, P. (Paolo), Fernández-Aranda, F. (Fernando), Gratacos, M. (Monica), Rybakowski, F. (Filip), Dmitrzak-Weglarz, M. (Monika), Kaprio, J. (Jaakko), Keski-Rahkonen, A. (Anna), Raevuori-Helkamaa, A. (Anu), Furth, E.F. (Eric) van, Slof-Op’t Landt, M.C.T. (Margarita C. T.), Hudson, J.I. (James I), Knudsen, G.P.S. (Gun Peggy S.), Monteleone, P. (Palmiero), Kaplan, A.S. (Allan S), Karwautz, A. (Andreas), Li, D. (Dong), Komaki, G. (Gen), Ando, T. (Tetsuya), Inoko, H. (Hidetoshi), Esko, T. (T.), Fischer, K. (Krista), Männik, K. (Katrin), Metspalu, A. (Andres), Baker, J.H. (Jessica H), Cone, R.D. (Roger D), Esko, T. (Tõnu), DeSocio, J.E. (Janiece E), Hilliard, C.E. (Christopher E), O’Toole, J.K. (Julie K), Pantel, J. (Jacques), Szatkiewicz, J.P. (Jin P), Taico, C. (Chrysecolla), Zerwas, S. (Stephanie), Trace, S.E. (Sara E), Davis, O.S.P. (Oliver S.), Helder, S. (Sietske), Bühren, K. (Katharina), Burghardt, R. (Roland), Imgart, H. (Hartmut), Scherag, A. (Andre), Boni, C. (Claudette), Ramoz, N. (Nicolas), Versini, A. (Audrey), Danner, U.N. (Unna N), de Kove, C. (Carolien), Hendriks, J. (Judith), Koeleman, B.P.C. (Bobby P. C.), Ophoff, R.A. (Roel), Strengman, E. (Eric), Bruson, A. (Alice), Clementi, M. (Maurizio), Degortes, D. (Daniela), Forzan, M. (Monica), Tenconi, E. (Elena), Docampo, E. (Elisa), Jiménez-Murcia, G.E.S. (Geòrgia Escaramí Susana), Lissowska, J. (Jolanta), Rajewski, A. (Andrzej), Szeszenia-Dabrowska, N. (Neonila), Slopien, A. (Agnieszka), Hauser, J. (J.), Karhunen, L. (Leila), Meulenbelt, I. (Ingrid), Slagboom, P.E. (Eline), Tortorella, A. (Alfonso), Maj, M. (Mario), Dedoussis, G.V. (George), Dedoussis, G.V. (G. V.), Koeleman, B.P.C. (Bobby), Gonidakis, F. (Fragiskos), Tziouvas, K. (Konstantinos), Tsitsika, A. (Artemis), Papezova, H. (Hana), Slachtova, L. (Lenka), Martaskova, D. (Debora), Kennedy, J.L., Levitan, R.D. (Robert D), Yilmaz, Z. (Zeynep), Huemer, J. (Julia), Koubek, D. (Doris), Merl, E. (Elisabeth), Wagner, G. (Gudrun), Lichtenstein, P. (Paul), Breen, G. (Gerome), Cohen-Woods, S. (Sarah), Farmer, A.E. (Anne E), Mcguffin, P. (Peter), Cichon, S. (Sven), Giegling, I. (Ina), Herms, S. (Stefan), Rujescu, D. (Dan), Schreiber, S. (Stefan), Wichmann, H.E. (Heinz Erich), Sladek, R. (Rob), Gambaro, G. (Giovanni), Soranzo, N. (Nicole), Julia, A. (Antonio), Marsal, S. (Sara), Rabionet, R. (Raquel), Gaborieau, V. (Valerie), Dick, D.M. (Danielle), Palotie, A. (A.), Ripatti, S. (Samuli), Widen, E., Espeseth, T. (Thomas), Lundervold, A.J. (Astri), Reinvang, I. (Ivar), Steen, V.M. (Vidar), Le Hellard, S. (Stephanie), Mattingsdal, M. (Morten), Ntalla, I. (Ioanna), Bencko, V. (Vladimir), Foretova, L. (Lenka), Janout, V. (Vladimir), Navratilova, M. (Marie), Pinto, D. (Dalila), Scherer, S.W. (Stephen W), Carlberg, L. (Laura), Schosser, A. (Alexandra), Alfredsson, L. (Lars), Pinto, D. (Duane), Scherer, S.W. (Stephen), Padyukov, L. (Leonid), Finan, C. (Chris), Kalsi, G. (Gursharan), Roberts, M. (Marion), Logan, D.W. (Darren W), Peltonen, L. (Leena Johanna), Ritchie, G.R.S. (Graham R.S.), Barrett, J.C. (Jeffrey), Estivill, X. (Xavier), Sullivan, P.F. (Patrick), Anderson, C.A. (Carl A), McGinnis, R. (Ralph), Sambrook, J. (Jennifer), Stephens, J. (Jonathan), Ouwehand, W.H. (Willem), McArdle, P.F. (P. F.), Ring, S.M. (Susan), Strachan, D.P. (David), Alexander, G. (Graeme), Conlon, P.J. (Peter J), Dominiczak, A. (Anna), Duncanson, A. (Audrey), Padyukov, L. (L.), Langford, C. (Cordelia), Lord, G. (Graham), Conlon, P. (Peter), Sandford, R. (Richard), Sheerin, N. (Neil), Vannberg, F.O. (Frederik O), Blackburn, H. (Hannah), Maxwell, A.P. (A.), Edkins, T. (Ted), Gillman, M.W. (Matthew W.), Gray, E. (Emma), Hunt, S.E. (Sarah E), Nengut, S.-G. (Suna-Gumuscu), Potter, S.C. (Simon), Rich, S.S. (Stephen), Simpkin, D. (Douglas), Whittaker, P. (Pamela), Ang, W.Q. (Wei), Atalay, M. (Mustafa), Beijsterveldt, C.E.M. (Toos) van, Bergen, N. (N.), Benke, K. (K.), Berry, D. (Diane), Boomsma, D.I. (Dorret), Bradfield, J.P. (Jonathan), Charoen, P. (Pimphen), Coin, L. (Lachlan), Cooper, C. (C.), Cousminer, D.L. (Diana), Das, S. (Shikta), Elliott, P. (P.), Evans, D.M. (D. M.), Feenstra, B. (B.), Flexeder, C. (Claudia), Frayling, T.M. (Timothy), Freathy, R.M. (Rachel), Gaillard, R. (R.), Geller, F. (Frank), Groen-Blokhuis, M. (Maria), Goh, L.K. (L. K.), Guxens Junyent, M. (Mònica), Hattersley, A.T. (Andrew), Haworth, C.M.A. (Claire M.), Hadley, D. (D.), Heinrich, J. (J.), Hirschhorn, J.N. (Joel), Hocher, B. (Berthold), Holloway, J.W. (J. W.), Holst, J.J., Hottenga, J.J. (Jouke Jan), Horikoshi, M. (Momoko), Huikari, V. (Ville), Hypponen, E. (E.), Iñiguez, C. (C.), Jaddoe, V.W. (V. W.), Jarvelin, M.R. (M. R.), Kaakinen, M. (M.), Kilpeläinen, T.O. (Tuomas), Hypponen, E. (Elina), Kowgier, M. (Matthew), Lakka, T.A. (Timo), Cooper, C. (Charles), Lange, L.A. (Leslie), Lawlor, D.A. (D. A.), Lehtimäki, T. (Terho), Lewin, A. (Alex), Elliott, P. (Paul), Lindi, V. (Virpi), Maggi, R. (Reedik), Feenstra, B. (Bjarke), McCarthy, M.I. (M. I.), Melbye, M. (Mads), Middeldorp, C.M. (Christel), Millwood, I.Y. (Iona), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (D. O.), Murray, J.C. (Jeffrey), Nivard, M. (Michel), Nohr, C. (Christian), Oken, E. (Emily), Ong, K.K. (K. K.), O'Reilly, P.F. (P. F.), Palmer, C. (Cameron), Panoutsopoulou, K. (K.), Pararajasingham, J. (Jennifer), Pearson, E.R. (E. R.), Pennell, C.E. (Craig), Power, C. (Christopher), Price, T.S. (Thomas), Prokopenko, I. (Inga), Raitakari, O.T. (O. T.), Rodriguez, A. (A.), Salem, R.M. (Rany), Saw, S.M. (S. M.), Sebert, S. (S.), Siitonen, N. (Niina), Jaddoe, V.W.V. (Vincent), Sørensen, T.I.A. (Thorkild), Sovio, U. (Ulla), Lawlor, D.A. (Debbie), Sunyer, J. (J.), Taal, H.R. (Rob), Teo, Y.Y. (Y. Y.), Thiering, E. (Elisabeth), Tiesler, C. (C.), Timpson, N.J. (Nicholas), Uitterlinden, A.G. (André), Valcárcel, B. (Beatriz), Teo, Y.Y. (Yik Ying), White, S.J. (Stefan), Willemsen, G.A.H.M. (Gonneke), Wilson, J.F. (J. F.), Yaghootkar, H. (H.), Elks, C.E. (Cathy), Perry, J.R. (J. R.), Sulem, P. (Patrick), Chasman, D.I. (Daniel), Franceschini, N. (Nora), He, C. (C.), Lunetta, K.L. (Kathryn), Visser, J.A. (Jenny), Byrne, E.M. (E. M.), Gudbjartsson, D.F. (Daniel), Koller, D.L. (Daniel), Kutalik, Z. (Zoltán), Lin, P. (P.), Mangino, M. (Massimo), Byrne, E.M. (Enda), Smith, A.V. (Albert), Stolk, L. (Lisette), Wingerden, S. (Sophie) van, Zhao, J.H. (J. H.), Albrecht, E. (Eva), Corre, T. (Tanguy), Ingelsson, E. (Erik), Hayward, C. (Caroline), Magnusson, P.K. (Patrik), Smith, A.V. (Davey), Chanock, S.J. (Stephen), Warrington, M. (M.), Zgaga, L. (L.), Alavere, H. (Helene), Amin, N. (Najaf), Aspelund, T. (T.), Ulivi, S. (Shelia), Sunyer, J. (Jordi), Berenson, G. (Gerald), Bergmann, S.M. (Sven), Boerwinkle, E. (E.), Buring, J.E. (Julie), Busonero, F. (F.), Barroso, I.E. (Inês), Chanock, S.J. (S. J.), Warrington, N.M. (Nicole), Couper, D.J. (David), Coviello, A.D. (Andrea), Busonero, F., Faire, U. (Ulf) de, de Geus, E.J. (E. J.), Deloukas, P. (Panagiotis), Döring, A. (Angela), Davey Smith, G. (G.), Adamo, P. (Pio) d', Eiriksdottir, G. (Gudny), Geus, E.J.C. (Eco) de, Hagen, K. (Knut), Ferrucci, L. (L.), Folsom, A.R. (A. R.), Foroud, T. (T.), Garcia, M.E. (M.), Gasparini, P. (P.), Gieger, C. (Christian), Gudnason, V. (V.), Folsom, A.R. (Aaron), Hankinson, S.E. (S. E.), Ferreli, L. (Liana), Gasparini, P. (Paolo), Hernandez, D.G. (Dena), Hofman, A. (Albert), Hu, F.B. (F. B.), Illig, T. (T.), Jarvelin, M.-R. (Marjo-Riitta), Johnson, A.D. (Andrew), Karasik, D. (David), Khaw, K.T. (K. T.), Kiel, D.P. (Douglas P.), Kolcic, I. (Ivana), Kraft, P. (Peter), Launer, L.J. (Lenore), Laven, J.S. (J. S.), Li, S. (S.), Liu, J. (J.), Levy, D. (D.), Martin, N.G. (N. G.), Aspelund, T. (Thor), Nalls, M.A. (Michael), Navarro, P. (Pau), Nelis, M. (M.), Ness, A.R. (A. R.), Boerwinkle, E.A. (Eric), Oostra, B.A. (Ben), Peacock, M. (M.), Pare, G. (Guillame), Parker, A.N. (Alex), Pedersen, N.L. (Nancy), Cornelis, M. (Marilyn), Polasek, O. (Ozren), Plump, A.S. (A. S.), Peacock, M. (Munro), Porcu, E. (Eleonora), Rafnar, T. (Thorunn), Rice, J.P. (John), Rivadeneira, F. (F.), Sala, C. (Cinzia), Salomaa, V. (Veikko), Sanna, S. (Serena), Schlessinger, D. (D.), Scuteri, A. (A.), Segrè, A.V. (Ayellet), Foroud, T. (Tatiana), Srinivasan, S.R. (Sathanur), Tammesoo, M.L. (M. L.), Tikkanen, E. (Emmi), Toniolo, D. (Daniela), Scuteri, A. (Angelo), Tryggvadottir, L. (Laufey), Tyrer, J. (J.), Uda, M. (M.), van Dam, R.M. (R. M.), Meurs, J.B.J. (Joyce) van, Vollenweider, P. (Peter), Waeber, G. (Gérard), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weedon, M.N. (Michael), Wright, A.F. (Alan), Young, L. (L.), Zhai, G. (G.), Zhuang, W.V. (W. V.), Bierut, L.J. (L. J.), Boyd, H.A. (H. A.), Crisponi, L. (Laura), Demerath, E.W. (E. W.), Duijn, C.M. (Cornelia) van, Econs, M.J. (M. J.), Harris, T.B. (Tamara), Bierut, L.J. (Laura), Loos, R.J.F. (Ruth), Ridker, P.M. (Paul), Demerath, E.W. (Ellen), Streeten, E.A. (Elizabeth), Econs, M.J. (Michael), Thorsteinsdottir, U. (Unnur), Widen, E. (E.), Murabito, J. (Joanne), Ness, A.R. (Andrew), Spector, T.D. (Timothy), Crawford, S. (Steve), Crow, S. (Scott), Fichter, M.M. (M. M.), Halmi, K.A. (K. A.), Palotie, A. (Aarno), La Via, M. (Maria), Mitchell, J. (James), Strober, M. (Michael), Rotondo, A. (Alessandro), Woodside, D.B. (D Blake), Keel, P. (Pamela), Lilenfeld, L. (Lisa), Rivadeneira Ramirez, F. (Fernando), Magistretti, P. (Pierre), and Montgomery, G.W. (G. W.)
Abstract: The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the associa
Published: 2017
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82. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), Cupples, L.A. (Adrienne), Justice, A.E. (Anne), Winkler, T.W. (Thomas W.), Feitosa, M.F., Graff, M.J. (Maud J.L.), Fisher, V.A. (Virginia A.), Young, K. (Kristin), Barata, L. (Llilda), Deng, X. (Xuan), Czajkowski, J. (Jacek), Hadley, D. (David), Ngwa, J.S. (Julius S.), Ahluwalia, T.S. (Tarunveer Singh), Chu, A.Y. (Audrey Y), Heard-Costa, N.L. (Nancy), Lim, E. (Elise), Perez, J. (Jeremiah), Eicher, J.D. (John D.), Kutalik, Z. (Zoltán), Xue, L. (Luting), Mahajan, A. (Anubha), Renström, F. (Frida), Wu, J.M.W. (Joseph M. W.), Qi, Q., Ahmad, S. (Shafqat), Alfred, T. (Tamuno), Amin, N. (Najaf), Bielak, L.F. (Lawrence F.), Bonnefond, A. (Amélie), Bragg-Gresham, J.L. (Jennifer L.), Cadby, G. (Gemma), Chittani, M. (Martina), Coggeshall, S. (Scott), Corre, T. (Tanguy), Direk, N. (Nese), Eriksson, J. (Joel), Fischer, K. (Krista), Gorski, M. (Mathias), Harder, M.N. (Marie Neergaard), Horikoshi, M. (Momoko), Huang, T. (Tao), Huffman, J.E. (Jennifer), Jackson, A.U. (Anne), Justesen, J.M. (Johanne M.), Kanoni, S. (Stavroula), Kinnunen, L. (Leena), Kleber, M.E. (Marcus), Komulainen, P. (Pirjo), Kumari, M. (Meena), Lim, U. (Unhee), Luan, J., Lyytikäinen, L.-P. (Leo-Pekka), Mangino, M. (Massimo), Manichaikul, A. (Ani), Marten, J. (Jonathan), Middelberg, R.P.S. (Rita), Müller-Nurasyid, M. (Martina), Navarro, P. (Pau), Perusse, L. (Louis), Pervjakova, N. (Natalia), Sarti, C. (Cinzia), Smith, A.V. (Albert), Smith, J.A. (Jennifer A), Stanča'kova, A. (Alena), Strawbridge, R.J. (Rona), Stringham, H.M. (Heather M.), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Most, P.J. (Peter) van der, Vliet-Ostaptchouk, J.V. (Jana) van, Vedantam, S. (Sailaja), Verweij, N. (Niek), Vink, J.M. (Jacqueline), Vitart, V. (Veronique), Wu, Y. (Ying), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zimmermann, M.E. (Martina E.), Zubair, N. (Niha), Abecasis, G.R. (Gonçalo), Adair, L.S. (Linda S.), Afaq, S. (Saima), Afzal, U. (Uzma), Bakker, S.J.L. (Stephan), Bartz, T.M. (Traci M.), Beilby, J.P. (John), Bergman, R.N. (Richard), Bergmann, S. (Sven), Biffar, R. (Reiner), Blangero, J. (John), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin), Braga, D. (Daniele), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Campbell, H. (Harry), Chambers, J.C. (John C.), Collins, F.S. (Francis), Curran, J.E. (Joanne), Borst, G.J. (Gert) de, Craen, A.J. (Anton) de, Geus, E.J.C. (Eco) de, Dedoussis, G.V. (George), Delgado, G., Ruijter, H.M. (Hester ) den, Eiriksdottir, G. (Gudny), Eriksson, A.L. (Anna L.), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Ford, I. (Ian), Forrester, T. (Terrence), Gertow, K. (Karl), Gigante, B. (Bruna), Glorioso, N. (Nicola), Gong, J. (Jian), Grallert, H. (Harald), Grammer, T.B. (Tanja), Grarup, N. (Niels), Haitjema, S. (Saskia), Hallmans, G. (Göran), Hamsten, A. (Anders), Hansen, T. (Torben), Harris, T.B. (Tamara), Hartman, C.A. (C.), Hassinen, M. (Maija), Hastie, N. (Nick), Heath, A.C. (Andrew), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J., Hollensted, M. (Mette), Holmen, O.L. (Oddgeir L.), Homuth, G. (Georg), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Hung, J. (Joseph), Hutri-Kähönen, N. (Nina), Ingelsson, E. (Erik), James, A. (Alan), Jansson, J.-O. (John-Olov), Jarvelin, M.-R. (Marjo-Riitta), Jhun, M.A. (Min A.), Jørgensen, M.E. (Marit E.), Juonala, M. (Markus), Kähönen, M. (Mika), Karlsson, M. (Magnus), Koistinen, H.A. (Heikki A.), Kolcic, I. (Ivana), Kolovou, G. (Genovefa), Kooperberg, C. (Charles), Krämer, B.K. (Bernhard), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Launer, L.J. (Lenore), Leander, K. (Karin), Lee, N.R. (Nanette R.), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), Linneberg, A. (Allan), Lobbens, S. (Stéphane), Loh, M. (Marie), Lorentzon, M. (Mattias), Luben, R. (Robert), Lubke, G.H. (Gitta), Ludolph-Donislawski, A. (Anja), Lupoli, S. (Sara), Madden, P.A. (Pamela), Männikkö, R. (Reija), Marques-Vidal, P. (Pedro), Martin, N.G. (Nicholas), McKenzie, C.A. (Colin), McKnight, B. (Barbara), Mellström, D. (Dan), Menni, C. (Cristina), Montgomery, G.W. (Grant W.), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Peyser, P.A. (Patricia A.), Pisinger, C. (Charlotta), Porteous, D.J. (David J.), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rao, D.C. (D. C.), Rasmussen-Torvik, L.J. (Laura), Rawal, R. (Rajesh), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Rose, L.M. (Lynda M.), Bien, S.A. (Stephanie A.), Rudan, I. (Igor), Sanna, S. (Serena), Sarzynski, M.A. (Mark A.), Sattar, N. (Naveed), Savonen, K. (Kai), Schlessinger, D. (David), Scholtens, S. (Salome), Schurmann, C. (Claudia), Scott, R.A. (Robert), Sennblad, B. (Bengt), Siemelink, M.A. (Marten A.), Silbernagel, G. (Günther), Slagboom, P.E. (Eline), Snieder, H. (Harold), Staessen, J.A. (Jan A.), Stott, D.J. (David. J.), Swertz, M.A. (Morris A.), Swift, A.J. (Amy), Taylor, K.D. (Kent), Tayo, B. (Bamidele), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Vandenput, L. (Liesbeth), Vohl, M.-C. (Marie-Claude), Völzke, H. (Henry), Vonk, J.M. (Judith), Waeber, G. (Gérard), Waldenberger, M. (Melanie), Westendorp, R.G.J. (Rudi), Wild, S.H. (Sarah), Willemsen, G., Wolffenbuttel, B.H.R. (Bruce), Wong, A. (Andrew), Wright, A.F. (Alan), Zhao, W. (Wei), Zillikens, M.C. (Carola), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Böger, C.A. (Carsten), Boomsma, D.I. (Dorret), Bouchard, C. (Claude), Bruinenberg, M. (M.), Chasman, D.I. (Daniel), Ida Chen, Y.-D. (Yii-Der), Chines, P.S. (Peter), Cooper, R.S. (Richard S.), Cucca, F. (Francesco), Cusi, D. (Daniele), Faire, U. (Ulf) de, Ferrucci, L. (Luigi), Franks, P.W. (Paul), Froguel, P. (Philippe), Gordon-Larsen, P. (Penny), Grabe, H.J. (Hans Jörgen), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Hayward, C. (Caroline), Hveem, K. (Kristian), Johnson, A.D. (Andrew D.), Jukema, J.W. (Jan Wouter), Kardia, S.L.R. (Sharon), Kivimaki, M. (Mika), Kooner, J.S. (Jaspal S.), Kuh, D. (Diana), Laakso, M. (Markku), Lehtimäki, T. (Terho), Le Marchand, L. (Loic), März, W. (Winfried), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Morris, A.P. (Andrew), Ohlsson, C. (Claes), Palmer, L.J. (Lyle J.), Pasterkamp, G. (Gerard), Pedersen, O. (Oluf), Peters, A. (Annette), Peters, U. (Ulrike), Polasek, O. (Ozren), Psaty, B.M. (Bruce M.), Qi, L. (Lu), Rauramaa, R. (Rainer), Smith, B.H. (Blair), Sørensen, T.I.A. (Thorkild), Strauch, K. (Konstantin), Tiemeier, H.W. (Henning), Tremoli, E. (Elena), Van Der Harst, P. (Pim), Vestergaard, H. (Henrik), Vollenweider, P. (Peter), Wareham, N.J. (Nick), Weir, D.R. (David), Whitfield, J. (John), Wilson, J.F. (James F.), Tyrrell, A.W.R., Frayling, T.M. (Timothy M.), Barroso, I.E. (Inês), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Fox, C.S. (Caroline), Hirschhorn, J.N. (Joel), Hunter, D.J. (David J.), Spector, T.D. (Timothy), Strachan, D.P. (David), Duijn, C.M. (Cornelia) van, Heid, I.M. (Iris), Mohlke, K.L. (Karen), Marchini, J. (Jonathan), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Liu, C.-T. (Ching-Ti), Borecki, I.B. (Ingrid), North, K.E. (Kari), and Cupples, L.A. (Adrienne)
Abstract: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting
Published: 2017
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83. Rare and low-frequency coding variants alter human adult height

Author: Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), Lettre, G. (Guillaume), Marouli, E. (Eirini), Graff, M.J. (Maud J.L.), Medina-Gomez, C. (Carolina), Lo, K.S., Wood, A.R. (Andrew), Kjaer, T.R. (Troels R.), Fine, R.S. (Rebecca S.), Lu, Y. (Yingchang), Schurmann, C. (Claudia), Highland, H. (Heather), Rüeger, S. (Sina), Thorleifsson, G. (Gudmar), Justice, A.E. (Anne), Lamparter, D. (David), Stirrups, K. (Kathy), Turcot, V. (Valérie), Young, K.L. (Kristin L.), Winkler, T.W. (Thomas W.), Esko, T. (Tõnu), Karaderi, T. (Tugce), Locke, A. (Adam), Masca, N.G.D. (Nicholas G.D.), Ng, M.C.Y. (Maggie C.Y.), Mudgal, P. (Poorva), Rivas, M.A. (Manuel), Vedantam, S. (Sailaja), Mahajan, A. (Anubha), Guo, X. (Xiuqing), Abecasis, G.R. (Gonçalo), Aben, K.K.H. (Katja), Adair, L.S. (Linda), Alam, D.S. (Dewan S.), Albrecht, E. (Eva), Allin, K.H. (Kristine H), Allison, M.A. (Matthew), Amouyel, P. (Philippe), Appel, E.V. (Emil V.), Arveiler, D. (Dominique), Asselbergs, F.W. (Folkert), Auer, P. (Paul), Balkau, B. (Beverley), Banas, B. (Bernhard), Bang, L.E. (Lia E.), Benn, M. (Marianne), Bergmann, S. (Sven), Bielak, L.F. (Lawrence F.), Blüher, M. (Matthias), Boeing, H. (Heiner), Boerwinkle, E.A. (Eric), Böger, C.A. (Carsten), Bonnycastle, L.L. (Lori), Bork-Jensen, J. (Jette), Bots, M.L. (Michiel), Bottinger, E.P. (Erwin), Bowden, D.W. (Donald), Brandslund, I. (Ivan), Breen, G. (Gerome), Brilliant, M.H. (Murray H.), Broer, L. (Linda), Burt, A.D. (Alastair), Butterworth, A.S. (Adam), Carey, D.J. (David J.), Caulfield, M. (Mark), Chambers, J.C. (John), Chasman, D.I. (Daniel), Chen, Y.-D.I. (Yii-Der Ida), Chowdhury, R. (Rajiv), Christensen, C. (Cramer), Chu, A.Y. (Audrey), Cocca, M. (Massimiliano), Collins, F.S. (Francis), Cook, J.P. (James P.), Corley, J. (Janie), Galbany, J.C. (Jordi Corominas), Cox, A.J. (Amanda J.), Cuellar-Partida, G. (Gabriel), Danesh, J. (John), Davies, G. (Gail), Bakker, P.I.W. (Paul) de, Borst, G.J. (Gert) de, De Denus, S. (Simon), De Groot, M.C.H. (Mark C.H.), Mutsert, R. (Reneé) de, Deary, I.J. (Ian), Dedoussis, G.V. (George), Demerath, E.W. (Ellen), Hollander, A.I. (Anneke), Dennis, J. (Joe), Angelantonio, E. (Emanuele) di, Drenos, F. (Fotios), Du, M. (Mengmeng), Dunning, A.M. (Alison M.), Easton, D.F. (Douglas), Ebeling, T. (Tapani), Edwards, T.L. (Todd L.), Ellinor, P.T. (Patrick), Elliott, P. (Paul), Evangelou, E. (Evangelos), Farmaki, A.-E. (Aliki-Eleni), Faul, J.D. (Jessica D.), Feitosa, M.F. (Mary Furlan), Feng, S. (Shuang), Ferrannini, E. (Ele), Ferrario, M.M. (Marco M.), Ferrieres, J. (Jean), Florez, J.C. (Jose), Ford, I., Fornage, M. (Myriam), Franks, P.W. (Paul), Frikke-Schmidt, R. (Ruth), Galesloot, T.E. (Tessel), Gan, W. (Wei), Gandin, I. (Ilaria), Gasparini, P. (Paolo), Giedraitis, V. (Vilmantas), Giri, A. (Ayush), Girotto, S., Gordon, S.D. (Scott D.), Gordon-Larsen, P. (Penny), Gorski, M. (Mathias), Grarup, N. (Niels), Grove, M.L. (Megan), Gudnason, V. (Vilmundur), Gustafsson, S. (Stefan), Hansen, T. (T.), Harris, K.M. (Kathleen Mullan), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Hayward, C. (Caroline), He, L. (Liang), Heid, I.M. (Iris), Heikkilä, K. (Kauko), Helgeland, Ø. (Øyvind), Hernesniemi, J. (Jussi), Hewit, A.W. (Alex), Hocking, L.J. (Lynne), Hollensted, M. (Mette), Holmen, O.L. (Oddgeir), Hovingh, G.K. (Kees), Howson, J.M.M. (Joanna M.M.), Hoyng, C.B. (Carel), Huang, P.L. (Paul L.), Hveem, K. (Kristian), Ikram, M.K. (Kamran), Ingelsson, E. (Erik), Jackson, A.U. (Anne), Jansson, J.-H. (Jan-Håkan), Jarvik, G.P. (Gail), Jensen, G.B. (Gorm B.), Jhun, M.A. (Min A.), Jia, Y. (Yucheng), Jiang, X. (Xuejuan), Johansson, S. (Stefan), Jørgensen, M.E. (Marit E.), Jorgensen, T. (Torben), Jousilahti, P. (Pekka), Jukema, J.W. (Jan Wouter), Kahali, B. (Bratati), Kahn, R. (René), Kähönen, M. (Mika), Kamstrup, P.R. (Pia R.), Kanoni, S. (Stavroula), Kaprio, J. (Jaakko), Karaleftheri, M. (Maria), Kardia, S.L.R. (Sharon L.R.), Karpe, F. (Fredrik), Kee, F. (Frank), Keeman, J.N., Kiemeney, L.A.L.M. (Bart), Kitajima, H. (Hidetoshi), Kluivers, K.B. (Kirsten B.), Kocher, T., Komulainen, P. (Pirjo), Kontto, J. (Jukka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kriebel, J. (Jennifer), Kuivaniemi, H. (Helena), Küry, S. (Sébastien), Kuusisto, J. (Johanna), La Bianca, M. (Martina), Laakso, M. (Markku), Lakka, T.A. (Timo), Lange, E.M. (Ethan), Lange, L.A. (Leslie), Langefeld, C.D. (Carl), Langenberg, C. (Claudia), Larson, E.B. (Eric B.), Lee, I.-T. (I-Te), Lehtimäki, T. (Terho), Lewis, C.E. (Cora E.), Li, H. (Huaixing), Li, J. (Jin), Li-Gao, R. (Ruifang), Lin, H. (Honghuang), Lin, L.-A. (Li-An), Lin, X. (Xu), Kao, W.H.L. (Wen), Lindström, J. (Jaana), Linneberg, A. (Allan), Liu, Y. (Yeheng), Liu, Y. (YongMei), Lophatananon, A. (Artitaya), Luan, J. (Jian'An), Lubitz, S.A. (Steven), Lyytikäinen, L.-P. (Leo-Pekka), Mackey, D.A. (David A.), Madden, P.A. (Pamela), Manning, A.K. (Alisa), Männistö, S. (Satu), Marenne, G. (Gaëlle), Marten, J. (Jonathan), Martin, N.G. (Nicholas), Mazul, A.L. (Angela L.), Meidtner, K. (Karina), Metspalu, A. (Andres), Mitchell, P. (Paul), Mohlke, K.L. (Karen), Mook-Kanamori, D.O. (Dennis), Morgan, A. (Anna), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Müller-Nurasyid, M. (Martina), Munroe, P. (Patricia), Nalls, M.A. (Michael), Nauck, M. (Matthias), Nelson, C.P. (Christopher P.), Neville, M.J. (Matthew), Nielsen, S.F. (Sune), Nikus, K. (Kjell), Njolstad, P. (Pal), Nordestgaard, B.G. (Børge), Ntalla, I. (Ioanna), O'Connel, J.R. (Jeffrey R.), Oksa, H. (Heikki), Loohuis, L.M.O. (Loes M. Olde), Ophoff, R.A. (Roel), Owen, K.R. (Katharine R.), Packard, C.J. (Chris J.), Padmanabhan, S. (Sandosh), Palmer, C.N.A. (Colin), Pasterkamp, G. (Gerard), Patel, A.P. (Aniruddh), Pattie, A. (Alison), Pedersen, O. (Oluf), Peissig, P.L. (Peggy L.), Peloso, G.M. (Gina), Pennell, C.E. (Craig), Perola, M. (Markus), Perry, J.A. (James A.), Perry, J.R.B. (John R.B.), Person, A.D. (Anthony), Pirie, A. (Ailith), Polasek, O. (Ozren), Posthuma, D. (Danielle), Raitakari, O.T. (Olli T.), Rasheed, A. (Asif), Rauramaa, R. (Rainer), Reilly, D.F. (Dermot F.), Reiner, A. (Alexander), Renström, F. (Frida), Ridker, P.M. (Paul), Rioux, J.D. (John), Robertson, N.R. (Neil), Robino, A. (Antonietta), Rolandsson, O. (Olov), Rudan, I. (Igor), Ruth, K.S. (Katherine S.), Saleheen, D. (Danish), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Sandow, K. (Kevin), Sapkota, Y. (Yadav), Sattar, N. (Naveed), Schmidt, M.K. (Marjanka), Schreiner, P.J. (Pamela), Schulze, M.B. (Matthias B), Scott, R.A. (Robert), Segura-Lepe, M.P. (Marcelo P.), Shah, S.H. (Svati), Sim, X. (Xueling), Sivapalaratnam, S. (Suthesh), Small, K.S. (Kerrin), Smith, A.V. (Albert Vernon), Smith, J.A. (Jennifer A), Southam, L. (Lorraine), Spector, T.D. (Timothy), Speliotes, E.K. (Elizabeth K.), Starr, J.M. (John), Steinthorsdottir, V. (Valgerdur), Stringham, H.M. (Heather), Stumvoll, M. (Michael), Surendran, P. (Praveen), Hart't, L.M. (Leen M.), Tansey, K.E. (Katherine E.), Tardif, J.-C. (Jean-Claude), Taylor, K.D. (Kent), Teumer, A. (Alexander), Thompson, D. (Deborah), Thorsteinsdottir, U. (Unnur), Thuesen, B.H. (Betina H.), Tönjes, A. (Anke), Tromp, G. (Gerard), Trompet, S. (Stella), Tsafantakis, E. (Emmanouil), Tuomilehto, J. (Jaakko), Tybjaerg-Hansen, A. (Anne), Tyrer, J.P. (Jonathan), Uher, R., Uitterlinden, A.G. (André), Ulivi, S. (Sheila), Van Der Laan, S.W. (Sander W.), Van Der Leij, A.R. (Andries R.), Duijn, C.M. (Cornelia) van, Schoor, N.M. (Natasja) van, Setten, J. (Jessica) van, Varbo, A. (Anette), Varga, T.V. (Tibor V.), Varma, R. (Rohit), Velez Edwards, D.R. (Digna R.), Vermeulen, S.H.H.M. (Sita), Vestergaard, H. (Henrik), Vitart, V. (Veronique), Vogt, T.F. (Thomas F.), Vozzi, D. (Diego), Walker, M. (Mark), Wang, F. (Feijie), Wang, C.A. (Carol A.), Wang, S. (Shuai), Wang, Y. (Yiqin), Wareham, N.J. (Nicholas J.), Warren, H. (Helen), Wessel, J. (Jennifer), Willems, S.M. (Sara), Wilson, J.F. (James), Witte, D.R. (Deniel), Woods, M.O. (Michael), Wu, Y. (Ying), Yaghootkar, H. (Hanieh), Yao, J. (Jiefen), Yao, P. (Pang), Yerges-Armstrong, L.M. (Laura), Young, R. (Robin), Zeggini, E. (Eleftheria), Zhan, X. (Xiaowei), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhao, W. (Wei), Zheng, H. (He), Zhou, W. (Wei), Rotter, J.I. (Jerome I.), Boehnke, M. (Michael), Kathiresan, S. (Sekar), McCarthy, M.I. (Mark I.), Willer, C.J. (Cristen), Zwart, J-A. (John-Anker), Borecki, I.B. (Ingrid), Liu, D. (Dajiang), North, K.E. (Kari), Heard-Costa, N.L. (Nancy), Pers, T.H. (Tune), Lindgren, C.M. (Cecilia M.), Oxvig, C. (Claus), Kutalik, Z. (Zoltán), Rivadeneira Ramirez, F. (Fernando), Loos, R.J.F. (Ruth), Frayling, T.M. (Timothy), Hirschhorn, J.N. (Joel), Deloukas, P. (Panos), and Lettre, G. (Guillaume)
Abstract: Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of I
Published: 2017
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84. Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

Author: Graff, M.J. (Maud J.L.), Scott, R.A. (Robert), Justice, A.E. (Anne), Young, K.L. (Kristin L.), Feitosa, M.F. (Mary Furlan), Barata, L. (Llilda), Winkler, T.W. (Thomas W.), Chu, A.Y. (Audrey), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N.L. (Nancy), Hoed, M. (Marcel) den, Ahluwalia, T.S. (Tarunveer Singh), Qi, Q., Ngwa, J.S., Renström, F. (Frida), Quaye, L. (Lydia), Eicher, J.D. (John D.), Hayes, J.E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltán), Lim, E. (Elise), Luan, J. (Jian'An), Huffman, J.E. (Jennifer), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P.J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. (Pedro), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A.V. (Albert Vernon), Kumari, M. (Meena), Harder, M.N. (Marie Neergaard), Justesen, J.M. (Johanne M.), Kleber, M.E. (Marcus), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N.V. (Natalia), Whitfield, J.B. (John B.), Zhao, J.H. (Jing Hua), Stringham, H.M. (Heather), Lyytikäinen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G.A.H.M. (Gonneke), Peyrot, W.J. (Wouter ), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayşe), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L.F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Mägi, R. (Reedik), Most, P.J. (Peter) van der, Jackson, A.U. (Anne), Bragg-Gresham, J.L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, Å. (Åsa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L.S. (Linda), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J.P. (John), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Bertoni, A.G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borja, J.B. (Judith), Brage, S. (Soren), Busonero, F., Buyske, S. (Steven), Campbell, H. (Harry), Chines, P.S. (Peter), Collins, F.S. (Francis), Corre, T. (Tanguy), Smith, G.D. (George Davey), Delgado, G., Dueker, N. (Nicole), Dörr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Fu, M. (Mao), Færch, K. (Kristine), Gieger, C. (Christian), Gläser, S., Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grootheest, G. (Gerard) van, Harald, K. (Kennet), Hastie, N. (Nick), Havulinna, A.S. (Aki), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J. (Lynne), Holmens, O.L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), James, A. (Alan), Jansson, J.-O. (John-Olov), Jhun, M.A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. (Heikki), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Kähönen, M. (Mika), Lakka, T.A. (Timo), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lindgren, C.M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K.L. (Keri), Montgomery, G.W. (Grant W.), Moor, M.H.M. de, Mulas, A. (Antonella), Müller-Nurasyid, M. (Martina), Musk, A.W., Männikkö, R. (Reija), Männistö, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J.A. (Jennifer ), Nolte, I.M. (Ilja M.), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P.A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L.J. (Laura J.), Rawal, R. (Rajesh), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M.A. (Mark A.), Savonen, K. (Kai), Scott, W.R. (William R.), Sanna, S. (Serena), Shuldiner, A.R. (Alan), Sidney, S. (Steve), Silbernagel, G. (Günther), Smith, B.H., Smith, J.A. (Jennifer A), Snieder, H. (Harold), Stancáková, A. (Alena), Sternfeld, B. (Barbara), Swift, A.J. (Amy), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), Vliet-Ostaptchouk, J.V. (Jana) van, Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Waeber, G. (Gérard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Zubair, N. (Niha), Haiman, C.A. (Christopher), LeMarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Perusse, L. (Louis), Wilson, J.F. (James), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C.A. (Catharina A.), Tönjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L.J. (Lyle J.), Kardia, S.L.R. (Sharon L. R.), Rauramaa, R. (Rainer), Sørensen, T.I.A. (Thorkild), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B.W.J.H. (Brenda), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Lehtimäki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N.G. (Nicholas), Kuh, D. (Diana), Liu, Y. (YongMei), Linneberg, A. (Allan), März, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T.B. (Tamara), Gudnason, V. (Vilmundur), Völzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Göran), Hansen, T. (T.), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Weir, D.R. (David), Porteous, D.J. (David J.), Boerwinkle, E.A. (Eric), Chasman, D.I. (Daniel), Abecasis, G.R. (Gonçalo R.), Barroso, I.E. (Inês), McCarthy, M.I. (Mark I.), Frayling, T.M. (Timothy), O’Connell, J.R. (Jeffrey R.), Duijn, C.M. (Cornelia) van, Boehnke, M. (Michael), Heid, I.M. (Iris), Mohlke, K.L. (Karen), Strachan, D.P. (David), Fox, C.S. (Caroline), Liu, C.-T. (Ching-Ti), Hirschhorn, J.N. (Joel), Klein, R.J. (Robert J.), Johnson, A.D. (Andrew), Borecki, I.B. (Ingrid), Franks, P.W. (Paul), North, K.E. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), Kilpeläinen, T.O. (Tuomas), Graff, M.J. (Maud J.L.), Scott, R.A. (Robert), Justice, A.E. (Anne), Young, K.L. (Kristin L.), Feitosa, M.F. (Mary Furlan), Barata, L. (Llilda), Winkler, T.W. (Thomas W.), Chu, A.Y. (Audrey), Mahajan, A. (Anubha), Hadley, D. (David), Xue, L. (Luting), Workalemahu, T. (Tsegaselassie), Heard-Costa, N.L. (Nancy), Hoed, M. (Marcel) den, Ahluwalia, T.S. (Tarunveer Singh), Qi, Q., Ngwa, J.S., Renström, F. (Frida), Quaye, L. (Lydia), Eicher, J.D. (John D.), Hayes, J.E. (James E.), Cornelis, M. (Marilyn), Kutalik, Z. (Zoltán), Lim, E. (Elise), Luan, J. (Jian'An), Huffman, J.E. (Jennifer), Zhang, W. (Weihua), Zhao, W. (Wei), Griffin, P.J. (Paula J.), Haller, T. (Toomas), Ahmad, S. (Shafqat), Marques-Vidal, P. (Pedro), Bien, S. (Stephanie), Yengo, L. (Loic), Teumer, A. (Alexander), Smith, A.V. (Albert Vernon), Kumari, M. (Meena), Harder, M.N. (Marie Neergaard), Justesen, J.M. (Johanne M.), Kleber, M.E. (Marcus), Hollensted, M. (Mette), Lohman, K. (Kurt), Rivera, N.V. (Natalia), Whitfield, J.B. (John B.), Zhao, J.H. (Jing Hua), Stringham, H.M. (Heather), Lyytikäinen, L.-P. (Leo-Pekka), Huppertz, C. (Charlotte), Willemsen, G.A.H.M. (Gonneke), Peyrot, W.J. (Wouter ), Wu, Y. (Ying), Kristiansson, K. (Kati), Demirkan, A. (Ayşe), Fornage, M. (Myriam), Hassinen, M. (Maija), Bielak, L.F. (Lawrence F.), Cadby, G. (Gemma), Tanaka, T. (Toshiko), Mägi, R. (Reedik), Most, P.J. (Peter) van der, Jackson, A.U. (Anne), Bragg-Gresham, J.L. (Jennifer L.), Vitart, V. (Veronique), Marten, J. (Jonathan), Navarro, P. (Pau), Bellis, C. (Claire), Pasko, D. (Dorota), Johansson, Å. (Åsa), Snitker, S. (Soren), Cheng, Y.-C. (Yu-Ching), Eriksson, J. (Joel), Lim, U. (Unhee), Aadahl, M. (Mette), Adair, L.S. (Linda), Amin, N. (Najaf), Balkau, B. (Beverley), Auvinen, J. (Juha), Beilby, J.P. (John), Bergman, R.N. (Richard N.), Bergmann, S.M. (Sven), Bertoni, A.G. (Alain G.), Blangero, J. (John), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borja, J.B. (Judith), Brage, S. (Soren), Busonero, F., Buyske, S. (Steven), Campbell, H. (Harry), Chines, P.S. (Peter), Collins, F.S. (Francis), Corre, T. (Tanguy), Smith, G.D. (George Davey), Delgado, G., Dueker, N. (Nicole), Dörr, M. (Marcus), Ebeling, T. (Tapani), Eiriksdottir, G. (Gudny), Esko, T. (Tõnu), Faul, J.D. (Jessica D.), Fu, M. (Mao), Færch, K. (Kristine), Gieger, C. (Christian), Gläser, S., Gong, J. (Jian), Gordon-Larsen, P. (Penny), Grallert, H. (Harald), Grammer, T.B. (Tanja B), Grarup, N. (Niels), Grootheest, G. (Gerard) van, Harald, K. (Kennet), Hastie, N. (Nick), Havulinna, A.S. (Aki), Hernandez, D.G. (Dena), Hindorff, L.A. (Lucia A), Hocking, L.J. (Lynne), Holmens, O.L. (Oddgeir L.), Holzapfel, C. (Christina), Hottenga, J.J. (Jouke Jan), Huang, J. (Jian), Huang, T. (Tao), Hui, J. (Jennie), Huth, C. (Cornelia), Hutri-Kähönen, N. (Nina), James, A. (Alan), Jansson, J.-O. (John-Olov), Jhun, M.A. (Min A.), Juonala, M. (Markus), Kinnunen, L. (Leena), Koistinen, H. (Heikki), Kolcic, I. (Ivana), Komulainen, P. (Pirjo), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Kähönen, M. (Mika), Lakka, T.A. (Timo), Launer, L.J. (Lenore), Lehne, B. (Benjamin), Lindgren, C.M. (Cecilia M.), Lorentzon, M. (Mattias), Luben, R.N. (Robert), Marre, M. (Michel), Milaneschi, Y. (Yuri), Monda, K.L. (Keri), Montgomery, G.W. (Grant W.), Moor, M.H.M. de, Mulas, A. (Antonella), Müller-Nurasyid, M. (Martina), Musk, A.W., Männikkö, R. (Reija), Männistö, S. (Satu), Narisu, N. (Narisu), Nauck, M. (Matthias), Nettleton, J.A. (Jennifer ), Nolte, I.M. (Ilja M.), Oldehinkel, A.J. (Albertine), Olden, M. (Matthias), Ong, K.K. (Ken K.), Padmanabhan, S. (Sandosh), Paternoster, L. (Lavinia), Perez, J. (Jeremiah), Perola, M. (Markus), Peters, A. (Annette), Peters, U. (Ulrike), Peyser, P.A. (Patricia A.), Prokopenko, I. (Inga), Puolijoki, H. (Hannu), Raitakari, O.T. (Olli T.), Rankinen, T. (Tuomo), Rasmussen-Torvik, L.J. (Laura J.), Rawal, R. (Rajesh), Ridker, P.M. (Paul), Rose, L.M. (Lynda), Rudan, I. (Igor), Sarti, C. (Cinzia), Sarzynski, M.A. (Mark A.), Savonen, K. (Kai), Scott, W.R. (William R.), Sanna, S. (Serena), Shuldiner, A.R. (Alan), Sidney, S. (Steve), Silbernagel, G. (Günther), Smith, B.H., Smith, J.A. (Jennifer A), Snieder, H. (Harold), Stancáková, A. (Alena), Sternfeld, B. (Barbara), Swift, A.J. (Amy), Tammelin, T. (Tuija), Tan, S.-T. (Sian-Tsung), Thorand, B. (Barbara), Thuillier, D. (Dorothee), Vandenput, L. (Liesbeth), Vestergaard, H. (Henrik), Vliet-Ostaptchouk, J.V. (Jana) van, Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Waeber, G. (Gérard), Walker, M. (Mark), Wild, S. (Sarah), Wong, A. (Andrew), Wright, A.F. (Alan), Zillikens, M.C. (Carola), Zubair, N. (Niha), Haiman, C.A. (Christopher), LeMarchand, L. (Loic), Gyllensten, U. (Ulf), Ohlsson, C. (Claes), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Perusse, L. (Louis), Wilson, J.F. (James), Hayward, C. (Caroline), Polasek, O. (Ozren), Cucca, F. (Francesco), Hveem, K. (Kristian), Hartman, C.A. (Catharina A.), Tönjes, A. (Anke), Bandinelli, S. (Stefania), Palmer, L.J. (Lyle J.), Kardia, S.L.R. (Sharon L. R.), Rauramaa, R. (Rainer), Sørensen, T.I.A. (Thorkild), Tuomilehto, J. (Jaakko), Salomaa, V. (Veikko), Penninx, B.W.J.H. (Brenda), Geus, E.J.C. (Eco) de, Boomsma, D.I. (Dorret), Lehtimäki, T. (Terho), Mangino, M. (Massimo), Laakso, M. (Markku), Bouchard, C. (Claude), Martin, N.G. (Nicholas), Kuh, D. (Diana), Liu, Y. (YongMei), Linneberg, A. (Allan), März, W. (Winfried), Strauch, K. (Konstantin), Kivimaki, M. (Mika), Harris, T.B. (Tamara), Gudnason, V. (Vilmundur), Völzke, H. (Henry), Qi, L. (Lu), Jarvelin, M.-R. (Marjo-Riitta), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Froguel, P. (Philippe), Kooperberg, C. (Charles), Vollenweider, P. (Peter), Hallmans, G. (Göran), Hansen, T. (T.), Pedersen, O. (Oluf), Metspalu, A. (Andres), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Weir, D.R. (David), Porteous, D.J. (David J.), Boerwinkle, E.A. (Eric), Chasman, D.I. (Daniel), Abecasis, G.R. (Gonçalo R.), Barroso, I.E. (Inês), McCarthy, M.I. (Mark I.), Frayling, T.M. (Timothy), O’Connell, J.R. (Jeffrey R.), Duijn, C.M. (Cornelia) van, Boehnke, M. (Michael), Heid, I.M. (Iris), Mohlke, K.L. (Karen), Strachan, D.P. (David), Fox, C.S. (Caroline), Liu, C.-T. (Ching-Ti), Hirschhorn, J.N. (Joel), Klein, R.J. (Robert J.), Johnson, A.D. (Andrew), Borecki, I.B. (Ingrid), Franks, P.W. (Paul), North, K.E. (Kari), Cupples, L.A. (Adrienne), Loos, R.J.F. (Ruth), and Kilpeläinen, T.O. (Tuomas)
Abstract: Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
Published: 2017
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85. Large meta-analysis of genome-wide association studies identifies five loci for lean body mass.

Author: Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., Kiel, D.P., Zillikens, M.C., Demissie, S., Hsu, Y.H., Yerges-Armstrong, L.M., Chou, W.C., Stolk, L., Livshits, G., Broer, L., Johnson, T., Koller, D.L., Kutalik, Z., Luan, J., Malkin, I., Ried, J.S., Smith, A.V., Thorleifsson, G., Vandenput, L., Hua Zhao, J., Zhang, W., Aghdassi, A., Åkesson, K., Amin, N., Baier, L.J., Barroso, I., Bennett, D.A., Bertram, L., Biffar, R., Bochud, M., Boehnke, M., Borecki, I.B., Buchman, A.S., Byberg, L., Campbell, H., Campos Obanda, N., Cauley, J.A., Cawthon, P.M., Cederberg, H., Chen, Z., Cho, N.H., Jin Choi, H., Claussnitzer, M., Collins, F., Cummings, S.R., De Jager, P.L., Demuth, I., Dhonukshe-Rutten, RAM, Diatchenko, L., Eiriksdottir, G., Enneman, A.W., Erdos, M., Eriksson, J.G., Eriksson, J., Estrada, K., Evans, D.S., Feitosa, M.F., Fu, M., Garcia, M., Gieger, C., Girke, T., Glazer, N.L., Grallert, H., Grewal, J., Han, B.G., Hanson, R.L., Hayward, C., Hofman, A., Hoffman, E.P., Homuth, G., Hsueh, W.C., Hubal, M.J., Hubbard, A., Huffman, K.M., Husted, L.B., Illig, T., Ingelsson, E., Ittermann, T., Jansson, J.O., Jordan, J.M., Jula, A., Karlsson, M., Khaw, K.T., Kilpeläinen, T.O., Klopp, N., Kloth, JSL, Koistinen, H.A., Kraus, W.E., Kritchevsky, S., Kuulasmaa, T., Kuusisto, J., Laakso, M., Lahti, J., Lang, T., Langdahl, B.L., Launer, L.J., Lee, J.Y., Lerch, M.M., Lewis, J.R., Lind, L., Lindgren, C., Liu, Y., Liu, T., Ljunggren, Ö., Lorentzon, M., Luben, R.N., Maixner, W., McGuigan, F.E., Medina-Gomez, C., Meitinger, T., Melhus, H., Mellström, D., Melov, S., Michaëlsson, K., Mitchell, B.D., Morris, A.P., Mosekilde, L., Newman, A., Nielson, C.M., O'Connell, J.R., Oostra, B.A., Orwoll, E.S., Palotie, A., Parker, S., Peacock, M., Perola, M., Peters, A., Polasek, O., Prince, R.L., Räikkönen, K., Ralston, S.H., Ripatti, S., Robbins, J.A., Rotter, J.I., Rudan, I., Salomaa, V., Satterfield, S., Schadt, E.E., Schipf, S., Scott, L., Sehmi, J., Shen, J., Soo Shin, C., Sigurdsson, G., Smith, S., Soranzo, N., Stančáková, A., Steinhagen-Thiessen, E., Streeten, E.A., Styrkarsdottir, U., Swart, KMA, Tan, S.T., Tarnopolsky, M.A., Thompson, P., Thomson, C.A., Thorsteinsdottir, U., Tikkanen, E., Tranah, G.J., Tuomilehto, J., van Schoor, N.M., Verma, A., Vollenweider, P., Völzke, H., Wactawski-Wende, J., Walker, M., Weedon, M.N., Welch, R., Wichmann, H.E., Widen, E., Williams, FMK, Wilson, J.F., Wright, N.C., Xie, W., Yu, L., Zhou, Y., Chambers, J.C., Döring, A., van Duijn, C.M., Econs, M.J., Gudnason, V., Kooner, J.S., Psaty, B.M., Spector, T.D., Stefansson, K., Rivadeneira, F., Uitterlinden, A.G., Wareham, N.J., Ossowski, V., Waterworth, D., Loos, RJF, Karasik, D., Harris, T.B., Ohlsson, C., and Kiel, D.P.
Abstract: Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10(-8)) or suggestively genome wide (p < 2.3 × 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.
Published: 2017

86. Correction: Genome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.

Author: Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., Barata, L., Winkler, T.W., Chu, A.Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N.L., den Hoed, M., Ahluwalia, T.S., Qi, Q., Ngwa, J.S., Renström, F., Quaye, L., Eicher, J.D., Hayes, J.E., Cornelis, M., Kutalik, Z., Lim, E., Luan, J., Huffman, J.E., Zhang, W., Zhao, W., Griffin, P.J., Haller, T., Ahmad, S., Marques-Vidal, P.M., Bien, S., Yengo, L., Teumer, A., Smith, A.V., Kumari, M., Harder, M.N., Justesen, J.M., Kleber, M.E., Hollensted, M., Lohman, K., Rivera, N.V., Whitfield, J.B., Zhao, J.H., Stringham, H.M., Lyytikäinen, L.P., Huppertz, C., Willemsen, G., Peyrot, W.J., Wu, Y., Kristiansson, K., Demirkan, A., Fornage, M., Hassinen, M., Bielak, L.F., Cadby, G., Tanaka, T., Mägi, R., van der Most, P.J., Jackson, A.U., Bragg-Gresham, J.L., Vitart, V., Marten, J., Navarro, P., Bellis, C., Pasko, D., Johansson, Å., Snitker, S., Cheng, Y.C., Eriksson, J., Lim, U., Aadahl, M., Adair, L.S., Amin, N., Balkau, B., Auvinen, J., Beilby, J., Bergman, R.N., Bergmann, S., Bertoni, A.G., Blangero, J., Bonnefond, A., Bonnycastle, L.L., Borja, J.B., Brage, S., Busonero, F., Buyske, S., Campbell, H., Chines, P.S., Collins, F.S., Corre, T., Smith, G.D., Delgado, G.E., Dueker, N., Dörr, M., Ebeling, T., Eiriksdottir, G., Esko, T., Faul, J.D., Fu, M., Færch, K., Gieger, C., Gläser, S., Gong, J., Gordon-Larsen, P., Grallert, H., Grammer, T.B., Grarup, N., van Grootheest, G., Harald, K., Hastie, N.D., Havulinna, A.S., Hernandez, D., Hindorff, L., Hocking, L.J., Holmens, O.L., Holzapfel, C., Hottenga, J.J., Huang, J., Huang, T., Hui, J., Huth, C., Hutri-Kähönen, N., James, A.L., Jansson, J.O., Jhun, M.A., Juonala, M., Kinnunen, L., Koistinen, H.A., Kolcic, I., Komulainen, P., Kuusisto, J., Kvaløy, K., Kähönen, M., Lakka, T.A., Launer, L.J., Lehne, B., Lindgren, C.M., Lorentzon, M., Luben, R., Marre, M., Milaneschi, Y., Monda, K.L., Montgomery, G.W., De Moor, MHM, Mulas, A., Müller-Nurasyid, M., Musk, A.W., Männikkö, R., Männistö, S., Narisu, N., Nauck, M., Nettleton, J.A., Nolte, I.M., Oldehinkel, A.J., Olden, M., Ong, K.K., Padmanabhan, S., Paternoster, L., Perez, J., Perola, M., Peters, A., Peters, U., Peyser, P.A., Prokopenko, I., Puolijoki, H., Raitakari, O.T., Rankinen, T., Rasmussen-Torvik, L.J., Rawal, R., Ridker, P.M., Rose, L.M., Rudan, I., Sarti, C., Sarzynski, M.A., Savonen, K., Scott, W.R., Sanna, S., Shuldiner, A.R., Sidney, S., Silbernagel, G., Smith, B.H., Smith, J.A., Snieder, H., Stančáková, A., Sternfeld, B., Swift, A.J., Tammelin, T., Tan, S.T., Thorand, B., Thuillier, D., Vandenput, L., Vestergaard, H., van Vliet-Ostaptchouk, J.V., Vohl, M.C., Völker, U., Waeber, G., Walker, M., Wild, S., Wong, A., Wright, A.F., Zillikens, M.C., Zubair, N., Haiman, C.A., Lemarchand, L., Gyllensten, U., Ohlsson, C., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Pérusse, L., Wilson, J.F., Hayward, C., Polasek, O., Cucca, F., Hveem, K., Hartman, C.A., Tönjes, A., Bandinelli, S., Palmer, L.J., Kardia, SLR, Rauramaa, R., Sørensen, TIA, Tuomilehto, J., Salomaa, V., Penninx, BWJH, de Geus, EJC, Boomsma, D.I., Lehtimäki, T., Mangino, M., Laakso, M., Bouchard, C., Martin, N.G., Kuh, D., Liu, Y., Linneberg, A., März, W., Strauch, K., Kivimäki, M., Harris, T.B., Gudnason, V., Völzke, H., Qi, L., Järvelin, M.R., Chambers, J.C., Kooner, J.S., Froguel, P., Kooperberg, C., Vollenweider, P., Hallmans, G., Hansen, T., Pedersen, O., Metspalu, A., Wareham, N.J., Langenberg, C., Weir, D.R., Porteous, D.J., Boerwinkle, E., Chasman, D.I., CHARGE, Consortium, EPIC-InterAct, Consortium, PAGE, Consortium, Abecasis, G.R., Barroso, I., McCarthy, M.I., Frayling, T.M., O'Connell, J.R., van Duijn, C.M., Boehnke, M., Heid, I.M., Mohlke, K.L., Strachan, D.P., Fox, C.S., Liu, C.T., Hirschhorn, J.N., Klein, R.J., Johnson, A.D., Borecki, I.B., Franks, P.W., North, K.E., Cupples, L.A., Loos, RJF, Kilpeläinen, T.O., Graff, M., Scott, R.A., Justice, A.E., Young, K.L., Feitosa, M.F., Barata, L., Winkler, T.W., Chu, A.Y., Mahajan, A., Hadley, D., Xue, L., Workalemahu, T., Heard-Costa, N.L., den Hoed, M., Ahluwalia, T.S., Qi, Q., Ngwa, J.S., Renström, F., Quaye, L., Eicher, J.D., Hayes, J.E., Cornelis, M., Kutalik, Z., Lim, E., Luan, J., Huffman, J.E., Zhang, W., Zhao, W., Griffin, P.J., Haller, T., Ahmad, S., Marques-Vidal, P.M., Bien, S., Yengo, L., Teumer, A., Smith, A.V., Kumari, M., Harder, M.N., Justesen, J.M., Kleber, M.E., Hollensted, M., Lohman, K., Rivera, N.V., Whitfield, J.B., Zhao, J.H., Stringham, H.M., Lyytikäinen, L.P., Huppertz, C., Willemsen, G., Peyrot, W.J., Wu, Y., Kristiansson, K., Demirkan, A., Fornage, M., Hassinen, M., Bielak, L.F., Cadby, G., Tanaka, T., Mägi, R., van der Most, P.J., Jackson, A.U., Bragg-Gresham, J.L., Vitart, V., Marten, J., Navarro, P., Bellis, C., Pasko, D., Johansson, Å., Snitker, S., Cheng, Y.C., Eriksson, J., Lim, U., Aadahl, M., Adair, L.S., Amin, N., Balkau, B., Auvinen, J., Beilby, J., Bergman, R.N., Bergmann, S., Bertoni, A.G., Blangero, J., Bonnefond, A., Bonnycastle, L.L., Borja, J.B., Brage, S., Busonero, F., Buyske, S., Campbell, H., Chines, P.S., Collins, F.S., Corre, T., Smith, G.D., Delgado, G.E., Dueker, N., Dörr, M., Ebeling, T., Eiriksdottir, G., Esko, T., Faul, J.D., Fu, M., Færch, K., Gieger, C., Gläser, S., Gong, J., Gordon-Larsen, P., Grallert, H., Grammer, T.B., Grarup, N., van Grootheest, G., Harald, K., Hastie, N.D., Havulinna, A.S., Hernandez, D., Hindorff, L., Hocking, L.J., Holmens, O.L., Holzapfel, C., Hottenga, J.J., Huang, J., Huang, T., Hui, J., Huth, C., Hutri-Kähönen, N., James, A.L., Jansson, J.O., Jhun, M.A., Juonala, M., Kinnunen, L., Koistinen, H.A., Kolcic, I., Komulainen, P., Kuusisto, J., Kvaløy, K., Kähönen, M., Lakka, T.A., Launer, L.J., Lehne, B., Lindgren, C.M., Lorentzon, M., Luben, R., Marre, M., Milaneschi, Y., Monda, K.L., Montgomery, G.W., De Moor, MHM, Mulas, A., Müller-Nurasyid, M., Musk, A.W., Männikkö, R., Männistö, S., Narisu, N., Nauck, M., Nettleton, J.A., Nolte, I.M., Oldehinkel, A.J., Olden, M., Ong, K.K., Padmanabhan, S., Paternoster, L., Perez, J., Perola, M., Peters, A., Peters, U., Peyser, P.A., Prokopenko, I., Puolijoki, H., Raitakari, O.T., Rankinen, T., Rasmussen-Torvik, L.J., Rawal, R., Ridker, P.M., Rose, L.M., Rudan, I., Sarti, C., Sarzynski, M.A., Savonen, K., Scott, W.R., Sanna, S., Shuldiner, A.R., Sidney, S., Silbernagel, G., Smith, B.H., Smith, J.A., Snieder, H., Stančáková, A., Sternfeld, B., Swift, A.J., Tammelin, T., Tan, S.T., Thorand, B., Thuillier, D., Vandenput, L., Vestergaard, H., van Vliet-Ostaptchouk, J.V., Vohl, M.C., Völker, U., Waeber, G., Walker, M., Wild, S., Wong, A., Wright, A.F., Zillikens, M.C., Zubair, N., Haiman, C.A., Lemarchand, L., Gyllensten, U., Ohlsson, C., Hofman, A., Rivadeneira, F., Uitterlinden, A.G., Pérusse, L., Wilson, J.F., Hayward, C., Polasek, O., Cucca, F., Hveem, K., Hartman, C.A., Tönjes, A., Bandinelli, S., Palmer, L.J., Kardia, SLR, Rauramaa, R., Sørensen, TIA, Tuomilehto, J., Salomaa, V., Penninx, BWJH, de Geus, EJC, Boomsma, D.I., Lehtimäki, T., Mangino, M., Laakso, M., Bouchard, C., Martin, N.G., Kuh, D., Liu, Y., Linneberg, A., März, W., Strauch, K., Kivimäki, M., Harris, T.B., Gudnason, V., Völzke, H., Qi, L., Järvelin, M.R., Chambers, J.C., Kooner, J.S., Froguel, P., Kooperberg, C., Vollenweider, P., Hallmans, G., Hansen, T., Pedersen, O., Metspalu, A., Wareham, N.J., Langenberg, C., Weir, D.R., Porteous, D.J., Boerwinkle, E., Chasman, D.I., CHARGE, Consortium, EPIC-InterAct, Consortium, PAGE, Consortium, Abecasis, G.R., Barroso, I., McCarthy, M.I., Frayling, T.M., O'Connell, J.R., van Duijn, C.M., Boehnke, M., Heid, I.M., Mohlke, K.L., Strachan, D.P., Fox, C.S., Liu, C.T., Hirschhorn, J.N., Klein, R.J., Johnson, A.D., Borecki, I.B., Franks, P.W., North, K.E., Cupples, L.A., Loos, RJF, and Kilpeläinen, T.O.
Abstract: [This corrects the article DOI: 10.1371/journal.pgen.1006528.].
Published: 2017

87. Long-term physical activity: an exogenous risk factor for sporadic amyotrophic lateral sclerosis?

Author: Harwood, C.A., Westgate, K., Gunstone, S., Brage, S., Wareham, N.J., McDermott, C.J., and Shaw, P.J.
Abstract: Objectives: To conduct a geographically defined, UK-based case-control study, to examine any association between physical activity (PA) and amyotrophic lateral sclerosis (ALS).\ud \ud Methods: A novel historical PA questionnaire was designed, validated, and subsequently administered in individual face-to-face interviews of 175 newly diagnosed sporadic ALS cases and 317 age- and sex-matched community controls. Historical PA energy expenditure and time spent in vigorous-intensity PA were derived from questionnaire data and compared between cases and controls.\ud \ud Results: Participation in an extra 10kJ/kg/day of PA (equivalent to approximately 45minutes brisk walking) was consistently associated with an increased risk of ALS, with the strongest association observed for adulthood exercise-related PA (OR 1.47, 95% CI 1.10-1.97). An extra 10mins/day of vigorous PA was also associated with the odds of ALS (OR 1.03, 95% CI 1·01-1·05). Results were slightly attenuated following adjustment for smoking and educational attainment.\ud \ud Conclusions: To our knowledge this is the first study to demonstrate a positive association between ALS and PA participation using a specifically designed and validated historical PA questionnaire. Despite the well-established health benefits of PA, a high activity lifestyle may also be associated with elevated risk of ALS. Large-scale prospective studies in the future may help to confirm this association.
Published: 2016

88. PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

Author: Schmidt, A.F., Swerdlow, D.I., Holmes, M.V., Patel, R.S., Fairhurst-Hunter, Z., Lyall, D.M., Hartwig, F.P., Horta, B.L., Hypponen, E., Power, C., Moldovan, M., Iperen, E. van, Hovingh, G.K., Demuth, I., Norman, K., Steinhagen-Thiessen, E., Demuth, J., Bertram, L., Liu, T., Coassin, S., Willeit, J., Kiechl, S., Willeit, K., Mason, D., Wright, J., Morris, R., Wanamethee, G., Whincup, P., Ben-Shlomo, Y., McLachlan, S., Price, J.F., Kivimaki, M., Welch, C., Sanchez-Galvez, A., Marques-Vidal, P., Nicolaides, A., Panayiotou, A.G., Onland-Moret, N.C., Schouw, Y.T. van der, Matullo, G., Fiorito, G., Guarrera, S., Sacerdote, C., Wareham, N.J., Langenberg, C., Scott, R., Luan, J.A., Bobak, M., Malyutina, S.A., Pajak, A., Kubinova, R., Tamosiunas, A., Pikhart, H., Husemoen, L.L.N., Grarup, N., Pedersen, O., Hansen, T., Linneberg, A., Simonsen, K.S., Cooper, J., Humphries, S.E., Brilliant, M., Kitchner, T., Hakonarson, H., Carrell, D.S., McCarty, C.A., Kirchner, H.L., Larson, E.B., Crosslin, D.R., Andrade, M. de, Roden, D.M., Denny, J.C., Carty, C., Hancock, S., Attia, J., Holliday, E., Donnell, M.O., Yusuf, S., Chong, M., Pare, G., Harst, P. van der, Said, M.A., Eppinga, R.N., Verweij, N., Snieder, H., Christen, T., Mook-Kanamori, D.O., Gustafsson, S., Lind, L., Ingelsson, E., Pazoki, R., Franco, O., Hofman, A., Uitterlinden, A., Dehghan, A., Teumer, A., Baumeister, S., Dorr, M., Lerch, M.M., Volker, U., Volzke, H., Ward, J., Pell, J.P., Smith, D.J., Meade, T., Maitland-van der Zee, A.H., Baranova, E.V., Young, R., Ford, I., Campbell, A., Padmanabhan, S., Bots, M.L., Grobbee, D.E., Froguel, P., Thuillier, D., Balkau, B., Bonnefond, A., Cariou, B., Smart, M., Bao, Y., Kumari, M., Mahajan, A., Ridker, P.M., Chasman, D.I., Reiner, A.P., Lange, L.A., Ritchie, M.D., Asselbergs, F.W., Casas, J.P., Keating, B.J., Preiss, D., Hingorani, A.D., Sattar, N., LifeLines Cohort Study Grp, UCLEB Consortium, Centre for Paediatric Epidemiology and Biostatistics, University College of London [London] (UCL), MRC Centre for Epidemiology of Child Health, UCL Institute of Child Health, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Dept. of Gastroenterology, Hepatology and Endocrinology, Neuroepidemiology of Ageing Research Unit, Imperial College London, Institut des Sciences Moléculaires (ISM), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Université Sciences et Technologies - Bordeaux 1-Université Montesquieu - Bordeaux 4-Institut de Chimie du CNRS (INC), Division of Community Health Sciences, St George's University of London, Department of Social Medicine, University of Bristol [Bristol], Finnish Institute of Occupational Health of Helsinki, Department of Epidemiology and Public Health, Institute of Social and Preventive Medicine, Lausanne university hospital, Computer Science Department, University of Cyprus, Cyprus Institute of Neurology and Genetics, University Medical Center [Utrecht], Department of Genetics, Biology and Biochemistry, University of Turin, Institute for Scientific Interchange Foundation, Center for Cancer Prevention, CPO-Piemonte, Unità di epidemiologia dei tumori, Università degli studi di Torino (UNITO)-HuGeF Foundation, Medical Research Council Epidemiology Unit, University of Cambridge [UK] (CAM), Serono Genetics Institute S.A.[Evry], Serono Genetics Institute, Institute of Internal and Preventive Medicine Sibe rian Branch, Russian Academy of Medical Sciences, Institute of Internal Medicine, Novosibirsk State Medical University, Centre for Environmental Health, National Institute of Public Health [Prague], Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Copenhagen = Københavns Universitet (KU), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, Rigshospitalet [Copenhagen], Copenhagen University Hospital, BHF Laboratories, Rayne building, Department of Medicine, 5 University Street, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia]-Children’s Hospital of Philadelphia (CHOP ), Population Health Research Institute, Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen [Groningen], Augusta University - Medical College of Georgia, University System of Georgia (USG)-University System of Georgia (USG), Limnology, Ecology, Uppsala Universitet [Uppsala], Metacohorts Consortium, Erasmus University Medical Center [Rotterdam] (Erasmus MC), King‘s College London, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Institute for Community Medicine, Department of Oncology and Metabolism [Sheffield, UK], The University of Sheffield [Sheffield, U.K.], European Associated Laboratory [Sheffield, UK] (Sarcoma Research Unit), Robertson Centre for Biostatistics, University of Glasgow, Faculty of Medicine, University of Glasgow, Julius Center for Health Sciences and Primary Care, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), INSERM UMRS 1178, Institut de recherche en biothérapie (IRB), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Department of Pathological Biochemistry, Royal Infirmary, Wareham, Nicholas [0000-0003-1422-2993], Langenberg, Claudia [0000-0002-5017-7344], Luan, Jian'an [0000-0003-3137-6337], and Apollo - University of Cambridge Repository
Subjects: Blood Glucose, Cohort Studies, Diabetes Mellitus, Type 2, Case-Control Studies, [SDV]Life Sciences [q-bio], Genetic Variation, Humans, Genetic Predisposition to Disease, Cholesterol, LDL, Mendelian Randomization Analysis, Proprotein Convertase 9, Randomized Controlled Trials as Topic
Abstract: BACKGROUND:Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk.METHODS:In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores.FINDINGS:Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m2, -0·09 to 0·30).INTERPRETATION:PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.FUNDING:British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.
Published: 2016

89. Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

Author: Duarte-Salles, T. Misra, S. Stepien, M. Plymoth, A. Muller, D. Overvad, K. Olsen, A. Tjønneland, A. Baglietto, L. Severi, G. Boutron-Ruault, M.-C. Turzanski-Fortner, R. Kaaks, R. Boeing, H. Aleksandrova, K. Trichopoulou, A. Lagiou, P. Bamia, C. Pala, V. Palli, D. Mattiello, A. Tumino, R. Naccarati, A. Bueno-De-Mesquita, H.B. Peeters, P.H. Weiderpass, E. Quiros, J.R. Agudo, A. Sanchez-Cantalejo, E. Ardanaz, E. Gavrila, D. Dorronsoro, M. Werner, M. Hemmingsson, O. Ohlsson, B. Sjöberg, K. Wareham, N.J. Khaw, K.-T. Bradbury, K.E. Gunter, M.J. Cross, A.J. Riboli, E. Jenab, M. Hainaut, P. Beretta, L.
Subjects: stomatognathic system, neoplasms, digestive system diseases
Abstract: We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function, and a-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95% CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable = 1.30; 95% CI, 1.14-1.48). The association was stronger among cases diagnosed within 2 years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC = 0.86). For cases diagnosed within 2 years, the combination of OPN and AFP was best able to predict HCC risk (AUC = 0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within 2 years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis. © 2016 American Association for Cancer Research.
Published: 2016

90. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Ehret, G.B. Ferreira, T. Chasman, D.I. Jackson, A.U. Schmidt, E.M. Johnson, T. Thorleifsson, G. Luan, J. Donnelly, L.A. Kanoni, S. Petersen, A.-K. Pihur, V. Strawbridge, R.J. Shungin, D. Hughes, M.F. Meirelles, O. Kaakinen, M. Bouatia-Naji, N. Kristiansson, K. Shah, S. Kleber, M.E. Guo, X. Lyytikäinen, L.-P. Fava, C. Eriksson, N. Nolte, I.M. Magnusson, P.K. Salfati, E.L. Rallidis, L.S. Theusch, E. Smith, A.J.P. Folkersen, L. Witkowska, K. Pers, T.H. Joehanes, R. Kim, S.K. Lataniotis, L. Jansen, R. Johnson, A.D. Warren, H. Kim, Y.J. Zhao, W. Wu, Y. Tayo, B.O. Bochud, M. Absher, D. Adair, L.S. Amin, N. Arking, D.E. Axelsson, T. Baldassarre, D. Balkau, B. Bandinelli, S. Barnes, M.R. Barroso, I. Bevan, S. Bis, J.C. Bjornsdottir, G. Boehnke, M. Boerwinkle, E. Bonnycastle, L.L. Boomsma, D.I. Bornstein, S.R. Brown, M.J. Burnier, M. Cabrera, C.P. Chambers, J.C. Chang, I.-S. Cheng, C.-Y. Chines, P.S. Chung, R.-H. Collins, F.S. Connell, J.M. Döring, A. Dallongeville, J. Danesh, J. De Faire, U. Delgado, G. Dominiczak, A.F. Doney, A.S.F. Drenos, F. Edkins, S. Eicher, J.D. Elosua, R. Enroth, S. Erdmann, J. Eriksson, P. Esko, T. Evangelou, E. Evans, A. Fall, T. Farrall, M. Felix, J.F. Ferrières, J. Ferrucci, L. Fornage, M. Forrester, T. Franceschini, N. Franco, O.H. Franco-Cereceda, A. Fraser, R.M. Ganesh, S.K. Gao, H. Gertow, K. Gianfagna, F. Gigante, B. Giulianini, F. Goel, A. Goodall, A.H. Goodarzi, M.O. Gorski, M. Gräßler, J. Groves, C.J. Gudnason, V. Gyllensten, U. Hallmans, G. Hartikainen, A.-L. Hassinen, M. Havulinna, A.S. Hayward, C. Hercberg, S. Herzig, K.-H. Hicks, A.A. Hingorani, A.D. Hirschhorn, J.N. Hofman, A. Holmen, J. Holmen, O.L. Hottenga, J.-J. Howard, P. Hsiung, C.A. Hunt, S.C. Ikram, M.A. Illig, T. Iribarren, C. Jensen, R.A. Kähönen, M. Kang, H.M. Kathiresan, S. Keating, B.J. Khaw, K.-T. Kim, Y.K. Kim, E. Kivimaki, M. Klopp, N. Kolovou, G. Komulainen, P. Kooner, J.S. Kosova, G. Krauss, R.M. Kuh, D. Kutalik, Z. Kuusisto, J. Kvaløy, K. Lakka, T.A. Lee, N.R. Lee, I.-T. Lee, W.-J. Levy, D. Li, X. Liang, K.-W. Lin, H. Lin, L. Lindström, J. Lobbens, S. Männistö, S. Müller, G. Müller-Nurasyid, M. Mach, F. Markus, H.S. Marouli, E. McCarthy, M.I. McKenzie, C.A. Meneton, P. Menni, C. Metspalu, A. Mijatovic, V. Moilanen, L. Montasser, M.E. Morris, A.D. Morrison, A.C. Mulas, A. Nagaraja, R. Narisu, N. Nikus, K. O'Donnell, C.J. O'Reilly, P.F. Ong, K.K. Paccaud, F. Palmer, C.D. Parsa, A. Pedersen, N.L. Penninx, B.W. Perola, M. Peters, A. Poulter, N. Pramstaller, P.P. Psaty, B.M. Quertermous, T. Rao, D.C. Rasheed, A. Rayner, N.W. Renström, F. Rettig, R. Rice, K.M. Roberts, R. Rose, L.M. Rossouw, J. Samani, N.J. Sanna, S. Saramies, J. Schunkert, H. Sebert, S. Sheu, W.H.-H. Shin, Y.-A. Sim, X. Smit, J.H. Smith, A.V. Sosa, M.X. Spector, T.D. Stančáková, A. Stanton, A.V. Stirrups, K.E. Stringham, H.M. Sundstrom, J. Swift, A.J. Syvänen, A.-C. Tai, E.-S. Tanaka, T. Tarasov, K.V. Teumer, A. Thorsteinsdottir, U. Tobin, M.D. Tremoli, E. Uitterlinden, A.G. Uusitupa, M. Vaez, A. Vaidya, D. Van Duijn, C.M. Van Iperen, E.P.A. Vasan, R.S. Verwoert, G.C. Virtamo, J. Vitart, V. Voight, B.F. Vollenweider, P. Wagner, A. Wain, L.V. Wareham, N.J. Watkins, H. Weder, A.B. Westra, H.-J. Wilks, R. Wilsgaard, T. Wilson, J.F. Wong, T.Y. Yang, T.-P. Yao, J. Yengo, L. Zhang, W. Zhao, J.H. Zhu, X. Bovet, P. Cooper, R.S. Mohlke, K.L. Saleheen, D. Lee, J.-Y. Elliott, P. Gierman, H.J. Willer, C.J. Franke, L. Hovingh, G.K. Taylor, K.D. Dedoussis, G. Sever, P. Wong, A. Lind, L. Assimes, T.L. Njølstad, I. Schwarz, P.E.H. Langenberg, C. Snieder, H. Caulfield, M.J. Melander, O. Laakso, M. Saltevo, J. Rauramaa, R. Tuomilehto, J. Ingelsson, E. Lehtimäki, T. Hveem, K. Palmas, W. März, W. Kumari, M. Salomaa, V. Chen, Y.-D.I. Rotter, J.I. Froguel, P. Jarvelin, M.-R. Lakatta, E.G. Kuulasmaa, K. Franks, P.W. Hamsten, A. Wichmann, H.-E. Palmer, C.N.A. Stefansson, K. Ridker, P.M. Loos, R.J.F. Chakravarti, A. Deloukas, P. Morris, A.P. Newton-Cheh, C. Munroe, P.B.
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation. © 2016 Nature America, Inc. All rights reserved.
Published: 2016

91. Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Author: Hughes, D.J. Duarte-Salles, T. Hybsier, S. Trichopoulou, A. Stepien, M. Aleksandrova, K. Overvad, K. Tjønneland, A. Olsen, A. Affret, A. Fagherazzi, G. Boutron-Ruault, M.-C. Katzke, V. Kaaks, R. Boeing, H. Bamia, C. Lagiou, P. Peppa, E. Palli, D. Krogh, V. Panico, S. Tumino, R. Sacerdote, C. Bueno-De-Mesquita, H.B. Peeters, P.H. Engeset, D. Weiderpass, E. Lasheras, C. Agudo, A. Sánchez, M.J. Navarro, C. Ardanaz, E. Dorronsoro, M. Hemmingsson, O. Wareham, N.J. Khaw, K.-T. Bradbury, K.E. Cross, A.J. Gunter, M. Riboli, E. Romieu, I. Schomburg, L. Jenab, M.
Abstract: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. Objective: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. Design: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. Results: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-mg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). Conclusion: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. © 2016 American Society for Nutrition.
Published: 2016

92. Corrigendum: Rare coding variants and X-linked loci associated with age at menarche

Author: Lunetta, K.L., Day, F.R., Sulem, P., Ruth, K.S., Tung, J.Y., Hinds, D.A., Esko, T., Elks, C.E., Altmaier, E., He, C., Huffman, J.E., Mihailov, E., Porcu, E., Robino, A., Rose, L.M., Schick, U.M., Stolk, L., Teumer, A., Thompson, D.J., Traglia, M., Wang, C.A., Yerges-Armstrong, L.M., Antoniou, A.C., Barbieri, C., Coviello, A.D., Cucca, F., Demerath, E.W., Dunning, A.M., Gandin, I., Grove, M.L., Gudbjartsson, D.F., Hocking, L.J., Hofman, A., Huang, J., Jackson, R.D., Karasik, D., Kriebel, J., Lange, E.M., Lange, L.A., Langenberg, C., Li, X., Luan, J., Mägi, R., Morrison, A.C., Padmanabhan, S., Pirie, A., Polasek, O., Porteous, D.J., Reiner, A.P., Rivadeneira, F., Rudan, I., Sala, C.F., Schlessinger, D., Scott, R.A., Stöckl, D., Visser, J.A., Völker, U., Vozzi, D., Wilson, J.G., Zygmunt, M., EPIC-Interact Consortium (), Generation Scotland Consortium (), Boerwinkle, E., Buring, J.E., Crisponi, L., Easton, D.F., Hayward, C., Hu, F.B., Liu, S., Metspalu, A., Pennell, C.E., Ridker, P.M., Strauch, K., Streeten, E.A., Toniolo, D., Uitterlinden, A.G., Ulivi, S., Völzke, H., Wareham, N.J., Wellons, M., Franceschini, N., Chasman, D.I., Thorsteinsdottir, U., Murray, A., Stefansson, K., Murabito, J.M., Ong, K.K., and Perry, J.R.
Subjects: Adult, Adolescent, Genotype, Mutation, Missense, Immunoglobulins, Cell Cycle Proteins, Penetrance, AMP-Activated Protein Kinases, Autoantigens, White People, Young Adult, Gene Frequency, Genes, X-Linked, Humans, Aged, Menarche, Chromosomes, Human, X, Hypogonadism, Fatty Acids, Age Factors, Genetic Variation, Membrane Proteins, Proteins, RNA-Binding Proteins, Receptors, Neurokinin-3, Middle Aged, Corrigenda, Amides, Phenotype, Codon, Nonsense, Female, RNA Interference, Laminin, Energy Metabolism, Signal Transduction
Abstract: More than 100 loci have been identified for age at menarche by genome-wide association studies; however, collectively these explain only ∼3% of the trait variance. Here we test two overlooked sources of variation in 192,974 European ancestry women: low-frequency protein-coding variants and X-chromosome variants. Five missense/nonsense variants (in ALMS1/LAMB2/TNRC6A/TACR3/PRKAG1) are associated with age at menarche (minor allele frequencies 0.08-4.6%; effect sizes 0.08-1.25 years per allele; P5 × 10(-8)). In addition, we identify common X-chromosome loci at IGSF1 (rs762080, P=9.4 × 10(-13)) and FAAH2 (rs5914101, P=4.9 × 10(-10)). Highlighted genes implicate cellular energy homeostasis, post-transcriptional gene silencing and fatty-acid amide signalling. A frequently reported mutation in TACR3 for idiopathic hypogonatrophic hypogonadism (p.W275X) is associated with 1.25-year-later menarche (P=2.8 × 10(-11)), illustrating the utility of population studies to estimate the penetrance of reportedly pathogenic mutations. Collectively, these novel variants explain ∼0.5% variance, indicating that these overlooked sources of variation do not substantially explain the 'missing heritability' of this complex trait.
Published: 2015

93. Parental origin of sequence variants associated with complex diseases

Author: Voight, B.F., Raychaudhuri, S., Purcell, S., McCarroll, S.A., Segrè, A.V., Ardlie, K., Burtt, N.P., Crawford, G., Elliott, A.L., Green, T., Guiducci, C., Saxena, R., Daly, M.J., Florez, J.C., Altshuler, D., Meigs, J.B., Scott, L.J., Welch, R.P., Willer, C.J., Ganser, M., Jackson, A.U., Stringham, H.M., Abecasis, G.R., Boehnke, M., Steinthorsdottir, V., Thorleifsson, G., Kong, A., Walters, G.B., Thorsteinsdottir, U., Stefansson, K., Dina, C., Proença, C., Cauchi, S., Froguel, P., Zeggini, E., Bumpstead, S., Payne, F., Smith, N., Barroso, I., Ferreira, T., Elliott, K.S., Lindgren, C.M., Prokopenko, I., Rayner, N.W., Robertson, N.R., Morris, A.P., McCarthy, M.I., Huth, C., Grallert, H., Gieger, C., Klopp, N., Meitinger, T., Petersen, A.-K., Thorand, B., Wichmann, H.-E., Illig, T., Aulchenko, Y.S., Amin, N., Witteman, J., Hofman, A., Van Duijn, C.M., McCulloch, L.J., Bennett, A.J., Groves, C.J., Hassanali, N., Owen, K.R., Gloyn, A.L., Wu, G., Stein, L.D., Langenberg, C., Griffin, S., Wareham, N.J., Hoffmann, O.M., Hide, W.A., Dupuis, J., Qi, L., Kraft, P., Sun, Q., Hunter, D., Hu, F.B., Cornelis, M., VanDam, R., Van Hoek, M., Van Herpt, T., Sijbrands, E., Uitterlinden, A., Navarro, P., Balkau, B., Benediktsson, R., Sigurdsson, G., Blagieva, R., Boehm, B.O., Boerwinkle, E., Bonnycastle, L.L., Chines, P.S., Erdos, M.R., Morken, M.A., Narisu, N., Swift, A.J., Boström, K.B., Bravenboer, B., Charpentier, G., Couper, D.J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Fox, C.S., Franklin, C.S., Rudan, I., Grarup, N., Hadjadj, S., Thomas Sparsø, [No Value], Campbell, H., Wilson, J.F., Hansen, T., Pedersen, O., Herder, C., Roden, M., Isomaa, B., Tuomi, T., Johnson, P.R.V., Jørgensen, T., Kao, W.H.L., Kuusisto, J., Laakso, M., Lauritzen, T., Li, M., Lieverse, A., Lyssenko, V., Nilsson, P., Groop, L., Marre, M., Midthjell, K., Platou, C., Hveem, K., Perry, J.R.B., Shields, B.M., Weedon, M.N., Frayling, T.M., Hattersley, A.T., Rathmann, W., Strassburger, K., Rocheleau, G., Sladek, R., Sampson, M.J., Shrader, P., Tichet, J., Bergman, R.N., Collins, F.S., Gyllensten, U., Hitman, G.A., Mohlke, K.L., Pramstaller, P.P., Tuomilehto, J., Walker, M., Watanabe, R.M., Pankow, J.S., and deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland. kong@decode.is
Subjects: Male, CCCTC-Binding Factor, Iceland, Mothers, Breast Neoplasms, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Fathers, Genomic Imprinting, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Humans, SNP, Genetic Predisposition to Disease, Allele, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, Binding Sites, Multidisciplinary, Genome, Human, Chromosomes, Human, Pair 11, Haplotype, DNA Methylation, Pedigree, Repressor Proteins, Diabetes Mellitus, Type 2, Haplotypes, Carcinoma, Basal Cell, DNA methylation, Female, Human genome, Genomic imprinting, Chromosomes, Human, Pair 7, 030217 neurology & neurosurgery
Abstract: To access publisher full text version of this article. Please click on the hyperlink in Additional Links field Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site. info:eu-repo/grantAgreement/EC/FP7/218071
Published: 2009

94. Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes

Author: Webb, D.R., primary, Zaccardi, F., additional, Davies, M.J., additional, Griffin, S.J., additional, Wareham, N.J., additional, Simmons, R.K., additional, Rutten, G.E., additional, Sandbaek, A., additional, Lauritzen, T., additional, Borch-Johnsen, K., additional, and Khunti, K., additional
Published: 2017
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95. Association of Cardiometabolic Multimorbidity With Mortality The Emerging Risk Factors Collaboration

Author: Angelantonio, E. di, Kaptoge, S., Wormser, D., Willeit, P., Butterworth, A.S., Bansal, N., O'Keeffe, L.M., Gao, P., Wood, A.M., Burgess, S., Freitag, D.F., Pennells, L., Peters, S.A., Hart, C.L., Haheim, L.L., Gillum, R.F., Nordestgaard, B.G., Psaty, B.M., Yeap, B.B., Knuiman, M.W., Nietert, P.J., Kauhanen, J., Salonen, J.T., Kuller, L.H., Simons, L.A., Schouw, Y.T. van der, Barrett-Connor, E., Selmer, R., Crespo, C.J., Rodriguez, B., Verschuren, W.M.M., Salomaa, V., Svardsudd, K., Harst, P. van der, Bjorkelund, C., Wilhelmsen, L., Wallace, R.B., Brenner, H., Amouyel, P., Barr, E.L.M., Iso, H., Onat, A., Trevisan, M., D'Agostino, R.B., Cooper, C., Kavousi, M., Welin, L., Roussel, R., Hu, F.B., Sato, S., Davidson, K.W., Howard, B.V., Leening, M., Rosengren, A., Dorr, M., Deeg, D.J.H., Kiechl, S., Stehouwer, C.D.A., Nissinen, A., Giampaoli, S., Donfrancesco, C., Kromhout, D., Price, J.F., Peters, A., Meade, T.W., Casiglia, E., Lawlor, D.A., Gallacher, J., Nagel, D., Franco, O.H., Assmann, G., Dagenais, G.R., Jukema, J.W., Sundstrom, J., Woodward, M., Brunner, E.J., Khaw, K.T., Wareham, N.J., Whitsel, E.A., Njolstad, I., Hedblad, B., Wassertheil-Smoller, S., Engstrom, G., Rosamond, W.D., Selvin, E., Sattar, N., Thompson, S.G., Danesh, J., and Emerging Risk Factors Collaboratio
Published: 2015

96. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: The European prospective investigation into cancer and nutrition study (EPIC)

Author: Ekelund, U. Ward, H.A. Norat, T. Luan, J. May, A.M. Weiderpass, E. Sharp, S.J. Overvad, K. Østergaard, J.N. Tjønneland, A. Johnsen, N.F. Mesrine, S. Fournier, A. Fagherazzi, G. Trichopoulou, A. Lagiou, P. Trichopoulos, D. Li, K. Kaaks, R. Ferrari, P. Licaj, I. Jenab, M. Bergmann, M. Boeing, H. Palli, D. Sieri, S. Panico, S. Tumino, R. Vineis, P. Peeters, P.H. Monnikhof, E. Bueno-De-Mesquita, H.B. Quirós, J.R. Agudo, A. Sánchez, M.-J. Huerta, J.M. Ardanaz, E. Arriola, L. Hedblad, B. Wirfält, E. Sund, M. Johansson, M. Key, T.J. Travis, R.C. Khaw, K.-T. Brage, S. Wareham, N.J. Riboli, E.
Abstract: Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear. Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures. Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Centerspecific PAF associated with inactivity, body mass index (BMI; in kg/m2) (>30), and WC (≥102 cm for men, ≥88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures. Results: Significant interactions (PA × BMI and PA × WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity. Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health. © 2015 American Society for Nutrition.
Published: 2015

97. Genetic variation in FTO and mortality

Author: Zimmermann, E., Angquist, L.H., Mirza, S.S., Zhao, J.H., Chasman, D.I., Fischer, K., Qi, Q., Smith, A.V., Thinggaard, M., Jarczok, M.N., Nalls, M.A., Trompet, S., Timpson, N.J., Schmidt, B., Jackson, A.U., Lyytikainen, L.P., Verweij, N., Mueller-Nurasyid, M., Vikstrom, M., Marques-Vidal, P., Wong, A., Meidtner, K., Middelberg, R.P., Strawbridge, R.J., Christiansen, L., Kyvik, K.O., Hamsten, A., Jaaskelainen, T., Tjonneland, A., Eriksson, J.G., Whitfield, J.B., Boeing, H., Hardy, R., Vollenweider, P., Leander, K., Peters, A., Harst, P. van der, Kumari, M., Lehtimaki, T., Meirhaeghe, A., Tuomilehto, J., Jockel, K.H., Ben-Shlomo, Y., Sattar, N., Baumeister, S.E., Smith, G.D., Casas, J.P., Houston, D.K., Marz, W., Christensen, K., Gudnason, V., Hu, F.B., Metspalu, A., Ridker, P.M., Wareham, N.J., Loos, R.J.F., Tiemeier, H., Sonestedt, E., Sorensen, T.I.A., The FTO-Mortality Collaborating, Epidemiology, Surgery, Erasmus MC other, Child and Adolescent Psychiatry / Psychology, FTO-Mortality Collaborating Group, Orho-Melander, M., Zillikens, C., Ikram, A., Hofman, A., Luan, J., Khaw, KT., Rose, LM., Läll, K., Mägi, R., Qi, L., Sun, Q., Harris, TB., Launer, LJ., Eiriksdottir, G., Kleber, ME., Delgado, G., Liu, Y., Garcia, M., Teumer, A., Grabe, H., Homuth, G., Jukema, JW., Ford, I., de Craen AJ., Gallacher, J., Yarnell, J., Mahabadi, AA., Nöthen, MM., Erbel, R., Stringham, HM., Boehnke, M., Amouyel, P., Ferrières, J., Arveiler, D., Kähönen, M., Nikus, K., Nieminen, T., Sanchez, A., Kivimaki, M., van Vliet-Ostaptchouk JV., Hampel, R., Thorand, B., De Faire, U., Nyberg, F., Kuh, D., Martin, NG., Montgomery, GW., Heath, AC., Madden, PA., Osmond, C., Pulizzi, N., Roswall, N., Halkjaer, J., Overvad, K., Uusitupa, M., Kinnunen, L., Lindström, J., Saramies, J., Keinänen-Kiukaanniemi, S., Uusitalo, H., Hussi, E., Baldassarre, D., Veglia, F., Humphries, S., Tremoli, E., and Heitmann, B.
Subjects: obesity, nutritional and metabolic diseases, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genetic Variation, Proteins, mortality, Polymorphism, Single Nucleotide, Article, Body Mass Index, meta-analysis, Observational Studies as Topic, Humans, Genetic Predisposition to Disease, Waist Circumference, FTO, Adiposity, Genome-Wide Association Study
Abstract: Previously, a single nucleotide polymorphism (SNP), rs9939609, in the FTO gene showed a much stronger association with all-cause mortality than expected from its association with body mass index (BMI), body fat mass index (FMI) and waist circumference (WC). This finding implies that the SNP has strong pleiotropic effects on adiposity and adiposity-independent pathological pathways that leads to increased mortality. To investigate this further, we conducted a meta-analysis of similar data from 34 longitudinal studies including 169,551 adult Caucasians among whom 27,100 died during follow-up. Linear regression showed that the minor allele of the FTO SNP was associated with greater BMI (n = 169,551; 0.32 kg m(-2) ; 95% CI 0.28-0.32, P
Published: 2015

98. Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

Author: Wessel, J. Chu, A.Y. Willems, S.M. Wang, S. Yaghootkar, H. Brody, J.A. Dauriz, M. Hivert, M.-F. Raghavan, S. Lipovich, L. Hidalgo, B. Fox, K. Huffman, J.E. An, P. Lu, Y. Rasmussen-Torvik, L.J. Grarup, N. Ehm, M.G. Li, L. Baldridge, A.S. Stančáková, A. Abrol, R. Besse, C. Boland, A. Bork-Jensen, J. Fornage, M. Freitag, D.F. Garcia, M.E. Guo, X. Hara, K. Isaacs, A. Jakobsdottir, J. Lange, L.A. Layton, J.C. Li, M. Hua Zhao, J. Meidtner, K. Morrison, A.C. Nalls, M.A. Peters, M.J. Sabater-Lleal, M. Schurmann, C. Silveira, A. Smith, A.V. Southam, L. Stoiber, M.H. Strawbridge, R.J. Taylor, K.D. Varga, T.V. Allin, K.H. Amin, N. Aponte, J.L. Aung, T. Barbieri, C. Bihlmeyer, N.A. Boehnke, M. Bombieri, C. Bowden, D.W. Burns, S.M. Chen, Y. Chen, Y.-D. Cheng, C.-Y. Correa, A. Czajkowski, J. Dehghan, A. Ehret, G.B. Eiriksdottir, G. Escher, S.A. Farmaki, A.-E. Frånberg, M. Gambaro, G. Giulianini, F. Goddard, W.A. Goel, A. Gottesman, O. Grove, M.L. Gustafsson, S. Hai, Y. Hallmans, G. Heo, J. Hoffmann, P. Ikram, M.K. Jensen, R.A. Jørgensen, M.E. Jørgensen, T. Karaleftheri, M. Khor, C.C. Kirkpatrick, A. Kraja, A.T. Kuusisto, J. Lange, E.M. Lee, I.T. Lee, W.-J. Leong, A. Liao, J. Liu, C. Liu, Y. Lindgren, C.M. Linneberg, A. Malerba, G. Mamakou, V. Marouli, E. Maruthur, N.M. Matchan, A. McKean-Cowdin, R. McLeod, O. Metcalf, G.A. Mohlke, K.L. Muzny, D.M. Ntalla, I. Palmer, N.D. Pasko, D. Peter, A. Rayner, N.W. Renström, F. Rice, K. Sala, C.F. Sennblad, B. Serafetinidis, I. Smith, J.A. Soranzo, N. Speliotes, E.K. Stahl, E.A. Stirrups, K. Tentolouris, N. Thanopoulou, A. Torres, M. Traglia, M. Tsafantakis, E. Javad, S. Yanek, L.R. Zengini, E. Becker, D.M. Bis, J.C. Brown, J.B. Adrienne Cupples, L. Hansen, T. Ingelsson, E. Karter, A.J. Lorenzo, C. Mathias, R.A. Norris, J.M. Peloso, G.M. Sheu, W.H.-H. Toniolo, D. Vaidya, D. Varma, R. Wagenknecht, L.E. Boeing, H. Bottinger, E.P. Dedoussis, G. Deloukas, P. Ferrannini, E. Franco, O.H. Franks, P.W. Gibbs, R.A. Gudnason, V. Hamsten, A. Harris, T.B. Hattersley, A.T. Hayward, C. Hofman, A. Jansson, J.-H. Langenberg, C. Launer, L.J. Levy, D. Oostra, B.A. O'Donnell, C.J. O'Rahilly, S. Padmanabhan, S. Pankow, J.S. Polasek, O. Province, M.A. Rich, S.S. Ridker, P.M. Rudan, I. Schulze, M.B. Smith, B.H. Uitterlinden, A.G. Walker, M. Watkins, H. Wong, T.Y. Zeggini, E. Laakso, M. Borecki, I.B. Chasman, D.I. Pedersen, O. Psaty, B.M. Shyong Tai, E. Van Duijn, C.M. Wareham, N.J. Waterworth, D.M. Boerwinkle, E. Linda Kao, W.H. Florez, J.C. Loos, R.J.F. Wilson, J.G. Frayling, T.M. Siscovick, D.S. Dupuis, J. Rotter, J.I. Meigs, J.B. Scott, R.A. Goodarzi, M.O.
Abstract: Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01mmoll-1, P=3.4 × 10-12), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035pmolinsulin mmolglucose-1, P=0.048), but higher 2-h glucose (β=0.16±0.05mmoll-1, P=4.3 × 10-4). We identify a gene-based association with FG at G6PC2 (p SKAT =6.8 × 10-6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004mmoll-1, P=1.3 × 10-8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. © 2015 Macmillan Publishers Limited. All rights reserved.
Published: 2015

99. Does the importance of dietary costs for fruit and vegetable intake vary by socioeconomic position?

Author: Mackenbach, J.D., Brage, S., Forouhi, N.G., Griffin, S.J., Wareham, N.J., Monsivais, P., Epidemiology and Data Science, and EMGO - Lifestyle, overweight and diabetes
Published: 2015

100. TERT gene harbors multiple variants associated with pancreatic cancer susceptibility

Author: Campa, D. Rizzato, C. Stolzenberg-Solomon, R. Pacetti, P. Vodicka, P. Cleary, S.P. Capurso, G. Bueno-De-Mesquita, H.B. Werner, J. Gazouli, M. Butterbach, K. Ivanauskas, A. Giese, N. Petersen, G.M. Fogar, P. Wang, Z. Bassi, C. Ryska, M. Theodoropoulos, G.E. Kooperberg, C. Li, D. Greenhalf, W. Pasquali, C. Hackert, T. Fuchs, C.S. Mohelnikova-Duchonova, B. Sperti, C. Funel, N. Dieffenbach, A.K. Wareham, N.J. Buring, J. Holcátová, I. Costello, E. Zambon, C.-F. Kupcinskas, J. Risch, H.A. Kraft, P. Bracci, P.M. Pezzilli, R. Olson, S.H. Sesso, H.D. Hartge, P. Strobel, O. Małecka-Panas, E. Visvanathan, K. Arslan, A.A. Pedrazzoli, S. Souček, P. Gioffreda, D. Key, T.J. Talar-Wojnarowska, R. Scarpa, A. Mambrini, A. Jacobs, E.J. Jamroziak, K. Klein, A. Tavano, F. Bambi, F. Landi, S. Austin, M.A. Vodickova, L. Brenner, H. Chanock, S.J. Delle Fave, G. Piepoli, A. Cantore, M. Zheng, W. Wolpin, B.M. Amundadottir, L.T. Canzian, F.
Abstract: A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio=0.85; 95% confidence interval=0.80-0.90, p=8.3 × 10-8). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r2=0.07, D′=0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p=3.0 × 10-5), rs4583925 (p=4.0 × 10-5) and rs2735948 (p=5.0 × 10-5). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants. What's new? Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools. © 2015 UICC.
Published: 2015

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