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1. Short term associations of ambient nitrogen dioxide with daily total, cardiovascular, and respiratory mortality:multilocation analysis in 398 cities

Author

Meng, X. (Xia), Liu, C. (Cong), Chen, R. (Renjie), Sera, F. (Francesco), Vicedo-Cabrera, A. M. (Ana Maria), Milojevic, A. (Ai), Guo, Y. (Yuming), Tong, S. (Shilu), Coelho, M. d. (Micheline de Sousa Zanotti Stagliorio), Saldiva, P. H. (Paulo Hilario Nascimento), Lavigne, E. (Eric), Correa, P. M. (Patricia Matus), Ortega, N. V. (Nicolas Valdes), Garcia, S. O. (Samuel Osorio), Kysely, J. (Jan), Urban, A. (Ales), Orru, H. (Hans), Maasikmets, M. (Marek), Jaakkola, J. J. (Jouni J. K.), Ryti, N. (Niilo), Huber, V. (Veronika), Schneider, A. (Alexandra), Katsouyanni, K. (Klea), Analitis, A. (Antonis), Hashizume, M. (Masahiro), Honda, Y. (Yasushi), Ng, C. F. (Chris Fook Sheng), Nunes, B. (Baltazar), Teixeira, J. P. (Joao Paulo), Holobaca, I. H. (Iulian Horia), Fratianni, S. (Simona), Kim, H. (Ho), Tobias, A. (Aurelio), Iniguez, C. (Carmen), Forsberg, B. (Bertil), Astrom, C. (Christofer), Ragettli, M. S. (Martina S.), Guo, Y. L. (Yue-Liang Leon), Pan, S.-C. (Shih-Chun), Li, S. (Shanshan), Bell, M. L. (Michelle L.), Zanobetti, A. (Antonella), Schwartz, J. (Joel), Wu, T. (Tangchun), Gasparrini, A. (Antonio), and Kan, H. (Haidong)

Abstract

Objective: To evaluate the short term associations between nitrogen dioxide (NO₂) and total, cardiovascular, and respiratory mortality across multiple countries/regions worldwide, using a uniform analytical protocol. Design: Two stage, time series approach, with overdispersed generalised linear models and multilevel meta-analysis. Setting: 398 cities in 22 low to high income countries/regions. Main outcome measures: Daily deaths from total (62.8 million), cardiovascular (19.7 million), and respiratory (5.5 million) causes between 1973 and 2018. Results: On average, a 10 μg/m³ increase in NO₂ concentration on lag 1 day (previous day) was associated with 0.46% (95% confidence interval 0.36% to 0.57%), 0.37% (0.22% to 0.51%), and 0.47% (0.21% to 0.72%) increases in total, cardiovascular, and respiratory mortality, respectively. These associations remained robust after adjusting for co-pollutants (particulate matter with aerodynamic diameter ≤10 μm or ≤2.5 μm (PM₁₀ and PM2.5, respectively), ozone, sulfur dioxide, and carbon monoxide). The pooled concentration-response curves for all three causes were almost linear without discernible thresholds. The proportion of deaths attributable to NO₂ concentration above the counterfactual zero level was 1.23% (95% confidence interval 0.96% to 1.51%) across the 398 cities. Conclusions: This multilocation study provides key evidence on the independent and linear associations between short term exposure to NO₂ and increased risk of total, cardiovascular, and respiratory mortality, suggesting that health benefits would be achieved by tightening the guidelines and regulatory limits of NO₂.

Published
2021

2. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration

Author

Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, Redline, S. (Susan), Noordam, R. (Raymond), Bos, M.M. (Maxime M.), Wang, H. (Heming), Winkler, T.W. (Thomas W.), Bentley, A.R. (Amy), Kilpeläinen, T.O. (Tuomas O.), Vries, P.S. (Paul) de, Sung, Y.J. (Yun Ju), Schwander, K., Cade, B., Manning, A.K. (Alisa), Aschard, H. (Hugues), Brown, M.R., Chen, H. (Han), Franceschini, N. (Nora), Musani, S.K. (Solomon K.), Richard, M. (Melissa), Vojinović, D. (Dina), Aslibekyan, S. (Stella), Bartz, T.M. (Traci M.), de Las Fuentes, L. (Lisa), Feitosa, M.F. (Mary Furlan), Horimoto, A.R. (Andrea R.), Ilkov, M. (Marjan), Kho, M. (Minjung), Kraja, A. (Aldi), Li, C. (Changwei), Lim, E. (Elise), Liu, Y. (YongMei), Mook-Kanamori, D.O. (Dennis O.), Rankinen, T. (Tuomo), Tajuddin, S.M. (Salman M.), Spek, A. (Ashley) van der, Wang, Z. (Zhe), Marten, J. (Jonathan), Laville, V. (Vincent), Alver, M. (Maris), Evangelou, E. (Evangelos), Graff, M.E. (Maria E.), He, M. (Meian), Kuhnel, B. (Brigitte), Lyytikäinen, L.-P. (Leo-Pekka), Marques-Vidal, P. (Pedro), Nolte, I.M. (Ilja), Palmer, N.D. (Nicholette), Rauramaa, R. (Rainer), Shu, X.-O. (Xiao-Ou), Snieder, H. (Harold), Weiss, S. (Stefan), Wen, W. (Wanqing), Yanek, L.R. (Lisa), Adolfo, C. (Correa), Ballantyne, C. (Christie), Bielak, L.F. (Lawrence F.), Biermasz, N.R., Boerwinkle, E.A. (Eric), Dimou, N. (Niki), Eiriksdottir, G. (Gudny), Gao, C. (Chuan), Gharib, S.A. (Sina), Gottlieb, D.J. (Daniel J.), Haba-Rubio, J. (José), Harris, T.B. (Tamara), Heikkinen, S. (Sami), Heinzer, R. (Raphaël), Hixson, J.E. (James E.), Homuth, G. (Georg), Ikram, M.A. (Arfan), Komulainen, P. (Pirjo), Krieger, J.E. (José), Lee, J. (Jiwon), Liu, J. (Jingmin), Lohman, K.K. (Kurt K.), Luik, A.I. (Annemarie), Mägi, R. (Reedik), Martin, L.W. (Lisa), Meitinger, T. (Thomas), Metspalu, A. (Andres), Milaneschi, Y. (Yuri), Nalls, M.A. (Michael), O´Connell, J.R., Peters, A. (Annette), Peyser, P.A. (Patricia A.), Raitakari, O. (Olli), Reiner, A. (Alexander), Rensen, P.C.N. (Patrick), Rice, T.K. (Treva K.), Rich, S.S. (Stephen), Roenneberg, T., Rotter, J.I. (Jerome I.), Schreiner, P.J. (Pamela), Shikany, J. (James), Sidney, S.S. (Stephen S.), Sims, M. (Mario), Sitlani, C.M. (Colleen M.), Sofer, T. (Tamar), Strauch, K. (Konstantin), Swertz, M.A. (Morris A.), Taylor, K.D. (Kent), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Völzke, H. (Henry), Waldenberger, M. (Melanie), Wallance, R.B. (Robert B.), van Dijk, K.W. (Ko Willems), Yu, C. (Caizheng), Zonderman, A.B. (Alan B.), Becker, D.M. (Diane), Elliott, P. (Paul), Esko, T. (Tõnu), Gieger, C. (Christian), Grabe, H.J. (Hans Jörgen), Lakka, T.A. (Timo), Lehtimäki, T. (Terho), North, K.E. (Kari), Penninx, B.W.J.H. (Brenda), Vollenweider, P. (Peter), Wagenknecht, L.E. (Lynne), Wu, T. (Tangchun), Xiang, Y.-B. (Yong-Bing), Zheng, W. (Wei), Arnett, D.K. (Donna), Bouchard, C. (Claude), Evans, M.K. (Michele), Gudnason, V. (Vilmundur), Kardia, S.L.R. (Sharon), Kelly, T.N. (Tanika N.), Kritchevsky, S.B. (Stephen), Loos, R.J.F. (Ruth), Pereira, A. (A.), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rotimi, C. (Charles), Zhu, X. (Xiaofeng), Amin, N. (Najaf), Cupples, L.A. (L Adrienne), Fornage, M. (Myriam), Fox, E.F. (Ervin F.), Guo, X. (Xiuqing), Gauderman, W.J. (W James), Rice, K.M. (Kenneth), Kooperberg, C. (Charles), Munroe, P. (Patricia), Liu, C.-T. (Ching-Ti), Morrison, A.C. (Alanna), Rao, D.C. (Dabeeru C.), Heemst, D. (Diana) van, and Redline, S. (Susan)

Abstract

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.

Published
2019
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3. 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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4. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Lu, L. (Lingeng), Lissowska, J. (Jolanta), Liu, J. (Jianjun), Lin, D. (Dongxin), Liao, L. (Linda), Liang, X. (Xiaolin), Li, D. (Donghui), Le-Marchand, L. (Loic), Landi, M.T. (María Teresa), Lan, Q. (Qing), LaCroix, A. (Andrea), Kurtz, R.C. (Robert C.), Krogh, V. (Vittorio), Kraft, P. (Peter), Kooperberg, C. (Charles), Kolonel, L.N. (Laurence N.), Koh, W.P. (Woon-Puay), Klein, R. (Robert), Klein, A.P. (Alison P.), Kim, Y.T. (Young Tae), Kim, Y.H. (Yeul Hong), Kim, H.N. (Hee Nam), Khaw, K.T. (Kay-Tee), Johansen, C. (Christoffer), Jenab, M. (Mazda), Hutchinson, A. (Amy), Hunter, D.J. (David J.), Hu, W. (Wei), Hu, N. (Nan), Hsiung, C.A. (Chao A.), Hoover, R.N. (Robert N.), Hong, Y.C. (Yun-Chul), Holly, E.A. (Elizabeth A.), Henriksson, R. (Roger), Harris, C.C. (Curtis C.), Hankinson, S.E. (Susan E.), Hallmans, G. (Goran), Haiman, C.A. (Christopher A.), Goldstein, A.M. (Alisa M.), Goldin, L. (Lynn), Giovannucci, E.L. (Edward L.), Gillanders, E.M. (Elizabeth M.), Giles, G.G. (Graham G.), Gaziano, J.M. (J. Michael), Gaudet, M.M. (Mia M.), Garcia-Closas, M. (Montserrat), Gapstur, S.M. (Susan M.), Gao, Y.T. (Yu-Tang), Gallinger, S. (Steven), Fuchs, C.S. (Charles S.), Friedenreich, C.M. (Christine M.), Fraumeni, J.F. (Joseph F.), Figueroa, J.D. (Jonine D.), Fan, J.H. (Jin-Hu), Epstein, C.G. (Caroline G.), Duell, E.J. (Eric J.), Doherty, J. (Jennifer), Ding, T. (Ti), De Vivo, I. (Immaculata), Davis, F.G. (Faith G.), Cullen, M. (Michael), Crous Bou, M. (Marta), Cook, L.S. (Linda S.), Chung, C.C. (Charles C.), Chen, K. (Kexin), Chen, C. (Constance), Chen, C. (Chu), Chatterjee, N. (Nilanjan), Chang, I.S. ( I-Shou), Chaffee, K.G. (Kari G.), Carreon, T. (Tania), Canzian, F. (Federico), Butler, M.A. (Mary A.), Buring, J.E. (Julie E.), Burdett, L. (Laurie), Bueno-de-Mesquita, H.B. (H. Bas), Brinton, L.A. (Louise A.), Bracci, P.M. (Paige M.), Bock, C.H. (Cathryn H.), Blot, W.J. (William J.), Black, A. (Amanda), Berndt, S.I. (Sonja I.), Chanock, S.J. (Stephen J.), Yeager, M. (Meredith), Dean, M.C. (Michael C.), Tucker, M. (Margaret), Rothman, N. (Nathaniel), Caporaso, N.E. (Neil E.), Perez-Jurado, L.A. (Luis A.), Beane-Freeman, L.E. (Laura E.), Ziegler, R.G. (Regina G.), Zhou, B. (Baosen), Zheng, W. (Wei), Zeleniuch-Jacquotte, A. (Anne), Zanetti, K.A. (Krista A.), Yu, K. (Kai), Yang, P.C. (Pan-Chyr), Yang, H.P. (Hannah P.), Xia, L. (Lucy), Wunder, J.S. (Jay S.), Arslan, A.A. (Alan A.), Wu, Y.L. (Yi-Long), Wu, Y.Q. (Yan Q.), Wu, T. (Tangchun), Wu, C. (Chen), Wong, M.P. (Maria Pik), Wolpin, B.M. (Brian M.), Wiencke, J.K. (John K.), White, E. (Emily), Wheeler, W. (William), Wentzensen, N. (Nicolas), Amundadottir, L. (Laufey), Wang, Z. (Zhaoming), Wang, J.C. (Jiu-Cun), Wacholder, S. (Sholom), Visvanathan, K. (Kala), Van Den Berg, D. (David), Tobias, G.S. (Geoffrey S.), Teras, L.R. (Lauren R.), Taylor, P.R. (Philip R.), Tang, Z.Z. (Ze-Zhong), Stram, D. (Daniel), Amos, C. (Christopher), Stolzenberg-Solomon, R.Z. (Rachael Z.), Stevens, V.L. (Victoria L.), Spitz, M.R. (Margaret R.), Silverman, D.T. (Debra T.), Shu, X.O. (Xiao-Ou), Shin, M.H. (Min-Ho), Sheng, X. (Xin), Shen, H. (Hongbing), Severi, G. (Gianluca), Setiawan, V.W. (Veronica Wendy), Aldrich, M.C. (Melinda C.), Seow, A. (Adeline), Schwartz, K.L. (Kendra L.), Schwartz, A.G. (Ann G.), Schumacher, F. (Fredrick), Savage, S.A. (Sharon A.), Ruder, A.M. (Avima M.), Rodriguez-Santiago, B. (Benjamin), Risch, H.A. (Harvey A.), Riboli, E. (Elio), Real, F.X. (Francisco X.), Abnet, C.C. (Christian C.), Rajaraman, P. (Preetha), Qiao, Y.L. (You-Lin), Purdue, M. (Mark), Prokunina-Olsson, L. (Ludmila), Prescott, J. (Jennifer), Pooler, L. (Loreall), Petersen, G. (Gloria), Peters, U. (Ulrike), Peplonska, B. (Beata), Park, J.Y. (Jae Yong), Jacobs, K. (Kevin), Orlow, I. (Irene), Olson, S.H. (Sara H.), Moore, L.E. (Lee E.), Mirabello, L. (Lisa), Melin, B.S. (Beatrice S.), McWilliams, R.R. (Robert R.), McNeill, L.H. (Lorna H.), Matsuo, K. (Keitaro), Malats, N. (Nuria), Magliocco, A.M. (Anthony M.), Hautman, C. (Christopher), Dagnall, C. (Casey), Hicks, B. (Belynda), Yang, Q. (Qi), Freedman, N.D. (Neal D.), Sampson, J. (Joshua), Karlins, E. (Eric), Zhou, W. (Weiyin), Mitchell, J.M. (J. Machiela), Machiela, M.J. (Mitchell J.), and Patiño-García, A. (Ana)

Subjects
Chromosome X, Age-related
Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016

5. Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

Author

He, M. (Meian), Xu, M. (Min), Zhang, B. (Ben), Liang, J. (Jun), Chen, P. (Ping), Lee, J.-Y. (Jong-Young), Johnson, T.A. (Todd A.), Li, H. (Huaixing), Yang, X. (Xiaobo), Dai, J. (Juncheng), Liang, L. (Liming), Gui, L. (Lixuan), Qi, Q., Huang, J. (Jian), Li, Y. (Yanping), Adair, L.S. (Linda), Aung, T. (Tin), Cai, Q. (Qiuyin), Cheng, C-Y. (Ching-Yu), Cho, M.-C. (Myeong-Chan), Cho, Y.S. (Yoon Shin), Chu, M. (Minjie), Cui, B. (Bin), Gao, Y. (Ying), Go, M.J. (Min Jin), Gu, D. (D.), Gu, W. (Weiqiong), Guo, H. (Huan), Hao, Y. (Yongchen), Hong, J. (Jie), Hu, Z. (Zhibin), Hu, Y. (Yanling), Huang, J. (Jianfeng), Hwang, J.-Y. (Joo-Yeon), Ikram, M.K. (Kamran), Jin, G. (Guangfu), Kang, D. (Daehee), Khor, C.C., Kim, B.-J. (Bong-Jo), Kim, H.T. (Hung Tae), Kubo, M. (Michiaki), Lee, J. (Jeannette), Lee, J. (Juyoung), Lee, N.R. (Nanette R.), Li, R. (Rui), Li, J. (Jun), Liu, J. (Jianjun), Longe, J. (Jirong), Lu, W. (Wei), Lu, X. (Xiangfeng), Miao, X. (Xiaoping), Okada, Y. (Yukinori), Ong, R.T.H. (Rick Twee-Hee), Qiu, G. (Gaokun), Seielstad, M. (Mark), Sim, X. (Xueling), Song, H. (Huaidong), Takeuchi, F. (Fumihiko), Tanaka, T. (Toshihiro), Taylor, P.R. (Phil R.), Wang, L. (Laiyuan), Wang, W. (Weiqing), Wang, Y. (Yiqin), Wu, C. (Chen), Wu, Y. (Ying), Xiang, Y.-B. (Yong-Bing), Yamamoto, K. (Ken), Yang, H. (Handong), Liao, M. (Ming), Yokota, M. (Mitsuhiro), Young, T. (Terri), Zhang, X. (Xiaomin), Kato, N. (Norihiro), Wang, Q. (Qing), Zheng, W. (Wei), Hu, F.B. (Frank), Lin, D. (Dongxin), Shen, H. (Hongbing), Teo, Y.Y. (Yik Ying), Mo, Z. (Zengnan), Wong, T.Y. (Tien Yin), Lin, X. (Xu), Mohlke, K.L. (Karen), Ning, G. (Guang), Tsunoda, T. (Tatsuhiko), Han, B.-G., Shu, X.-O. (Xiao-Ou), Tai, E.S. (Shyong), Wu, T. (Tangchun), Qi, L. (Lu), He, M. (Meian), Xu, M. (Min), Zhang, B. (Ben), Liang, J. (Jun), Chen, P. (Ping), Lee, J.-Y. (Jong-Young), Johnson, T.A. (Todd A.), Li, H. (Huaixing), Yang, X. (Xiaobo), Dai, J. (Juncheng), Liang, L. (Liming), Gui, L. (Lixuan), Qi, Q., Huang, J. (Jian), Li, Y. (Yanping), Adair, L.S. (Linda), Aung, T. (Tin), Cai, Q. (Qiuyin), Cheng, C-Y. (Ching-Yu), Cho, M.-C. (Myeong-Chan), Cho, Y.S. (Yoon Shin), Chu, M. (Minjie), Cui, B. (Bin), Gao, Y. (Ying), Go, M.J. (Min Jin), Gu, D. (D.), Gu, W. (Weiqiong), Guo, H. (Huan), Hao, Y. (Yongchen), Hong, J. (Jie), Hu, Z. (Zhibin), Hu, Y. (Yanling), Huang, J. (Jianfeng), Hwang, J.-Y. (Joo-Yeon), Ikram, M.K. (Kamran), Jin, G. (Guangfu), Kang, D. (Daehee), Khor, C.C., Kim, B.-J. (Bong-Jo), Kim, H.T. (Hung Tae), Kubo, M. (Michiaki), Lee, J. (Jeannette), Lee, J. (Juyoung), Lee, N.R. (Nanette R.), Li, R. (Rui), Li, J. (Jun), Liu, J. (Jianjun), Longe, J. (Jirong), Lu, W. (Wei), Lu, X. (Xiangfeng), Miao, X. (Xiaoping), Okada, Y. (Yukinori), Ong, R.T.H. (Rick Twee-Hee), Qiu, G. (Gaokun), Seielstad, M. (Mark), Sim, X. (Xueling), Song, H. (Huaidong), Takeuchi, F. (Fumihiko), Tanaka, T. (Toshihiro), Taylor, P.R. (Phil R.), Wang, L. (Laiyuan), Wang, W. (Weiqing), Wang, Y. (Yiqin), Wu, C. (Chen), Wu, Y. (Ying), Xiang, Y.-B. (Yong-Bing), Yamamoto, K. (Ken), Yang, H. (Handong), Liao, M. (Ming), Yokota, M. (Mitsuhiro), Young, T. (Terri), Zhang, X. (Xiaomin), Kato, N. (Norihiro), Wang, Q. (Qing), Zheng, W. (Wei), Hu, F.B. (Frank), Lin, D. (Dongxin), Shen, H. (Hongbing), Teo, Y.Y. (Yik Ying), Mo, Z. (Zengnan), Wong, T.Y. (Tien Yin), Lin, X. (Xu), Mohlke, K.L. (Karen), Ning, G. (Guang), Tsunoda, T. (Tatsuhiko), Han, B.-G., Shu, X.-O. (Xiao-Ou), Tai, E.S. (Shyong), Wu, T. (Tangchun), and Qi, L. (Lu)

Published
2015
Full Text
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