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1. Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes

Author: Albrechtsen, A, Grarup, N, Li, Y, Sparsø, T, Tian, G, Cao, H, Jiang, T, Kim, SY, Korneliussen, T, Li, Q, Nie, C, Wu, R, Skotte, L, Morris, AP, Ladenvall, C, Cauchi, S, Stančáková, A, Andersen, G, Astrup, A, Banasik, K, Bennett, AJ, Bolund, L, Charpentier, G, Chen, Y, Dekker, JM, Doney, ASF, Dorkhan, M, Forsen, T, Frayling, TM, Groves, CJ, Gui, Y, Hallmans, G, Hattersley, AT, He, K, Hitman, GA, Holmkvist, J, Huang, S, Jiang, H, Jin, X, Justesen, JM, Kristiansen, K, Kuusisto, J, Lajer, M, Lantieri, O, Li, W, Liang, H, Liao, Q, Liu, X, Ma, T, Ma, X, Manijak, MP, Marre, M, Mokrosiński, J, Morris, AD, Mu, B, Nielsen, AA, Nijpels, G, Nilsson, P, Palmer, CNA, Rayner, NW, Renström, F, Ribel-Madsen, R, Robertson, N, Rolandsson, O, Rossing, P, Schwartz, TW, Slagboom, PE, Sterner, M, D.E.S.I.R. Study Group, Tang, M, Tarnow, L, the DIAGRAM Consortium, Tuomi, T, van’t Riet, E, van Leeuwen, N, Varga, TV, Vestmar, MA, Walker, M, Wang, B, Wang, Y, Wu, H, Xi, F, Yengo, L, Yu, C, Zhang, X, Zhang, J, Zhang, Q, Zhang, W, Zheng, H, Zhou, Y, Altshuler, D, ‘t Hart, LM, Franks, PW, Balkau, B, Froguel, P, McCarthy, MI, Laakso, M, Groop, L, Christensen, C, and Brandslund, I
Subjects: Diabetes, Human Genome, Nutrition, Genetics, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Diabetes Mellitus, Type 2, Exome, Gene Frequency, Genotype, High-Throughput Nucleotide Sequencing, Humans, Hypertension, Polymorphism, Genetic, Polymorphism, Single Nucleotide, Exome sequencing, Genetic epidemiology, Lipids, Next-generation sequencing, Obesity, Type 2 diabetes, D.E.S.I.R. Study Group, DIAGRAM Consortium, Clinical Sciences, Paediatrics and Reproductive Medicine, Public Health and Health Services, Endocrinology & Metabolism
Abstract: Aims/hypothesisHuman complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes.MethodsThe study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 × 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 × 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 × 10(-10)).Conclusions/interpretationWe applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
Published: 2013

2. A saturated map of common genetic variants associated with human height

Author: Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022

3. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, Perry, JRB, Ruth, KS, Day, FR, Hussain, J, Martinez-Marchal, A, Aiken, CE, Azad, A, Thompson, DJ, Knoblochova, L, Abe, H, Tarry-Adkins, JL, Gonzalez, JM, Fontanillas, P, Claringbould, A, Bakker, OB, Sulem, P, Walters, RG, Terao, C, Turon, S, Horikoshi, M, Lin, K, Onland-Moret, NC, Sankar, A, Hertz, EPT, Timshel, PN, Shukla, V, Borup, R, Olsen, KW, Aguilera, P, Ferrer-Roda, M, Huang, Y, Stankovic, S, Timmers, PRHJ, Ahearn, TU, Alizadeh, BZ, Naderi, E, Andrulis, IL, Arnold, AM, Aronson, KJ, Augustinsson, A, Bandinelli, S, Barbieri, CM, Beaumont, RN, Becher, H, Beckmann, MW, Benonisdottir, S, Bergmann, S, Bochud, M, Boerwinkle, E, Bojesen, SE, Bolla, MK, Boomsma, DI, Bowker, N, Brody, JA, Broer, L, Buring, JE, Campbell, A, Campbell, H, Castelao, JE, Catamo, E, Chanock, SJ, Chenevix-Trench, G, Ciullo, M, Corre, T, Couch, FJ, Cox, A, Crisponi, L, Cross, SS, Cucca, F, Czene, K, Smith, GD, de Geus, EJCN, de Mutsert, R, De Vivo, I, Demerath, EW, Dennis, J, Dunning, AM, Dwek, M, Eriksson, M, Esko, T, Fasching, PA, Faul, JD, Ferrucci, L, Franceschini, N, Frayling, TM, Gago-Dominguez, M, Mezzavilla, M, Garcia-Closas, M, Gieger, C, Giles, GG, Grallert, H, Gudbjartsson, DF, Gudnason, V, Guenel, P, Haiman, CA, Hakansson, N, Hall, P, Hayward, C, He, C, He, W, Heiss, G, Hoffding, MK, Hopper, JL, Hottenga, JJ, Hu, F, Hunter, D, Ikram, MA, Jackson, RD, Joaquim, MDR, John, EM, Joshi, PK, Karasik, D, Kardia, SLR, Kartsonaki, C, Karlsson, R, Kitahara, CM, Kolcic, I, Kooperberg, C, Kraft, P, Kurian, AW, Kutalik, Z, La Bianca, M, LaChance, G, Langenberg, C, Launer, LJ, Laven, JSE, Lawlor, DA, Le Marchand, L, Li, J, Lindblom, A, Lindstrom, S, Lindstrom, T, Linet, M, Liu, Y, Liu, S, Luan, J, Magi, R, Magnusson, PKE, Mangino, M, Mannermaa, A, Marco, B, Marten, J, Martin, NG, Mbarek, H, McKnight, B, Medland, SE, Meisinger, C, Meitinger, T, Menni, C, Metspalu, A, Milani, L, Milne, RL, Montgomery, GW, Mook-Kanamori, DO, Mulas, A, Mulligan, AM, Murray, A, Nalls, MA, Newman, A, Noordam, R, Nutile, T, Nyholt, DR, Olshan, AF, Olsson, H, Painter, JN, Patel, AV, Pedersen, NL, Perjakova, N, Peters, A, Peters, U, Pharoah, PDP, Polasek, O, Porcu, E, Psaty, BM, Rahman, I, Rennert, G, Rennert, HS, Ridker, PM, Ring, SM, Robino, A, Rose, LM, Rosendaal, FR, Rossouw, J, Rudan, I, Rueedi, R, Ruggiero, D, Sala, CF, Saloustros, E, Sandler, DP, Sanna, S, Sawyer, EJ, Sarnowski, C, Schlessinger, D, Schmidt, MK, Schoemaker, MJ, Schraut, KE, Scott, C, Shekari, S, Shrikhande, A, Smith, AV, Smith, BH, Smith, JA, Sorice, R, Southey, MC, Spector, TD, Spinelli, JJ, Stampfer, M, Stoeckl, D, van Meurs, JBJ, Strauch, K, Styrkarsdottir, U, Swerdlow, AJ, Tanaka, T, Teras, LR, Teumer, A, thorsteinsdottir, U, Timpson, NJ, Toniolo, D, Traglia, M, Troester, MA, Truong, T, Tyrrell, J, Uitterlinden, AG, Ulivi, S, Vachon, CM, Vitart, V, Voelker, U, Vollenweider, P, Voelzke, H, Wang, Q, Wareham, NJ, Weinberg, CR, Weir, DR, Wilcox, AN, van Dijk, KW, Willemsen, G, Wilson, JF, Wolffenbuttel, BHR, Wolk, A, Wood, AR, Zhao, W, Zygmunt, M, Chen, Z, Li, L, Franke, L, Burgess, S, Deelen, P, Pers, TH, Grondahl, ML, Andersen, CY, Pujol, A, Lopez-Contreras, AJ, Daniel, JA, Stefansson, K, Chang-Claude, J, van der Schouw, YT, Lunetta, KL, Chasman, DI, Easton, DF, Visser, JA, Ozanne, SE, Namekawa, SH, Solc, P, Murabito, JM, Ong, KK, Hoffmann, ER, Roig, I, and Perry, JRB
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease.
Published: 2021

4. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author: Lagou, V, Mägi, R, Hottenga, JJ, Grallert, H, Perry, JR, Bouatia-Naji, N, Marullo, L, Rybin, D, Jansen, R, Min, JL, Dimas, AS, Ulrich, A, Zudina, L, Gådin, JR, Jiang, L, Faggian, A, Bonnefond, A, Fadista, J, Stathopoulou, MG, Isaacs, Aaron, Willems, SM, Navarro, P, Tanaka, T, Jackson, AU, Montasser, ME, O’Connell, JR, Bielak, LF, Webster, RJ, Saxena, R, Stafford, JM, Pourcain, BS, Timpson, NJ, Salo, P, Shin, SY, Amin, Najaf, Smith, AV, Li, G, Verweij, N, Goel, A, Ford, I, Johnson, PCD, Johnson, T, Kapur, K, Thorleifsson, G, Strawbridge, RJ, Rasmussen-Torvik, LJ, Esko, T, Mihailov, E, Fall, T, Fraser, RM, Mahajan, A, Kanoni, S, Giedraitis, V, Kleber, ME, Silbernagel, G, Meyer, J, Müller-Nurasyid, M, Ganna, A, Sarin, AP, Yengo, L, Shungin, D, Luan, J, Horikoshi, M, An, P, Sanna, S, Boettcher, Y, Rayner, NW, Nolte, IM, Zemunik, T, van Iperen, E, Kovacs, P, Hastie, ND, Wild, SH, McLachlan, S, Campbell, S, Polasek, O, Carlson, O, Egan, J, Kiess, W, Willemsen, G, Kuusisto, J, Laakso, M, Dimitriou, M, Hicks, AA, Rauramaa, R, Bandinelli, S, Thorand, B, Liu, Y, Miljkovic, I, Lind, L, Doney, A, Perola, M, Hingorani, A, Kivimaki, M, Kumari, M, Bennett, AJ, Groves, CJ, Herder, C, Koistinen, HA, Kinnunen, L, de Faire, U, Bakker, SJ, Uusitupa, M, Palmer, CN, Jukema, JW, Sattar, N, Pouta, A, Snieder, H, Boerwinkle, E, Pankow, JS, Magnusson, PKE, Krus, U, Scapoli, C, de Geus, EJCN, Blüher, M, Wolffenbuttel, BH, Province, MA, Abecasis, GR, Meigs, JB, Hovingh, GK, Lindström, J, Wilson, JF, Wright, AF, Dedoussis, GVZ, Bornstein, SR, Schwarz, PEH, Tönjes, A, Winkelmann, BR, Boehm, BO, März, W, Metspalu, A, Price, JF, Deloukas, P, Körner, A, Lakka, TA, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Bergman, RN, Tuomilehto, J, Wareham, NJ, Langenberg, C, Männistö, S, Franks, PW, Hayward, C, Vitart, V, Kaprio, J, Visvikis-Siest, S, Balkau, B, Altshuler, D, Rudan, I, Stumvoll, M, Campbell, H, Duijn, Cornelia, Gieger, C, Illig, T, Ferrucci, L, Pedersen, NL, Pramstaller, PP, Boehnke, M, Frayling, TM, Shuldiner, AR, Peyser, PA, Kardia, SL, Palmer, LJ, Penninx, BWJH, Meneton, P, Harris, TB, Navis, G, van der Harst, P, Smith, GD, Forouhi, NG, Loos, RJ, Salomaa, V, Soranzo, N, Boomsma, DI, Groop, L, Tuomi, T, Hofman, Bert, Munroe, PB, Gudnason, V, Siscovick, DS, Watkins, H, Lecoeur, C, Vollenweider, P, Franco-Cereceda, A, Eriksson, P, Jarvelin, M R R, Stefansson, K, Hamsten, A, Nicholson, G, Karpe, F, Dermitzakis, ET, Lindgren, CM, McCarthy, MI, Froguel, P, Kaakinen, MA, Lyssenko, V, Watanabe, RM, Ingelsson, E, Florez, JC, Dupuis, J, Barroso, I, Morris, AP, Prokopenko, I, Lagou, V, Mägi, R, Hottenga, JJ, Grallert, H, Perry, JR, Bouatia-Naji, N, Marullo, L, Rybin, D, Jansen, R, Min, JL, Dimas, AS, Ulrich, A, Zudina, L, Gådin, JR, Jiang, L, Faggian, A, Bonnefond, A, Fadista, J, Stathopoulou, MG, Isaacs, Aaron, Willems, SM, Navarro, P, Tanaka, T, Jackson, AU, Montasser, ME, O’Connell, JR, Bielak, LF, Webster, RJ, Saxena, R, Stafford, JM, Pourcain, BS, Timpson, NJ, Salo, P, Shin, SY, Amin, Najaf, Smith, AV, Li, G, Verweij, N, Goel, A, Ford, I, Johnson, PCD, Johnson, T, Kapur, K, Thorleifsson, G, Strawbridge, RJ, Rasmussen-Torvik, LJ, Esko, T, Mihailov, E, Fall, T, Fraser, RM, Mahajan, A, Kanoni, S, Giedraitis, V, Kleber, ME, Silbernagel, G, Meyer, J, Müller-Nurasyid, M, Ganna, A, Sarin, AP, Yengo, L, Shungin, D, Luan, J, Horikoshi, M, An, P, Sanna, S, Boettcher, Y, Rayner, NW, Nolte, IM, Zemunik, T, van Iperen, E, Kovacs, P, Hastie, ND, Wild, SH, McLachlan, S, Campbell, S, Polasek, O, Carlson, O, Egan, J, Kiess, W, Willemsen, G, Kuusisto, J, Laakso, M, Dimitriou, M, Hicks, AA, Rauramaa, R, Bandinelli, S, Thorand, B, Liu, Y, Miljkovic, I, Lind, L, Doney, A, Perola, M, Hingorani, A, Kivimaki, M, Kumari, M, Bennett, AJ, Groves, CJ, Herder, C, Koistinen, HA, Kinnunen, L, de Faire, U, Bakker, SJ, Uusitupa, M, Palmer, CN, Jukema, JW, Sattar, N, Pouta, A, Snieder, H, Boerwinkle, E, Pankow, JS, Magnusson, PKE, Krus, U, Scapoli, C, de Geus, EJCN, Blüher, M, Wolffenbuttel, BH, Province, MA, Abecasis, GR, Meigs, JB, Hovingh, GK, Lindström, J, Wilson, JF, Wright, AF, Dedoussis, GVZ, Bornstein, SR, Schwarz, PEH, Tönjes, A, Winkelmann, BR, Boehm, BO, März, W, Metspalu, A, Price, JF, Deloukas, P, Körner, A, Lakka, TA, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Bergman, RN, Tuomilehto, J, Wareham, NJ, Langenberg, C, Männistö, S, Franks, PW, Hayward, C, Vitart, V, Kaprio, J, Visvikis-Siest, S, Balkau, B, Altshuler, D, Rudan, I, Stumvoll, M, Campbell, H, Duijn, Cornelia, Gieger, C, Illig, T, Ferrucci, L, Pedersen, NL, Pramstaller, PP, Boehnke, M, Frayling, TM, Shuldiner, AR, Peyser, PA, Kardia, SL, Palmer, LJ, Penninx, BWJH, Meneton, P, Harris, TB, Navis, G, van der Harst, P, Smith, GD, Forouhi, NG, Loos, RJ, Salomaa, V, Soranzo, N, Boomsma, DI, Groop, L, Tuomi, T, Hofman, Bert, Munroe, PB, Gudnason, V, Siscovick, DS, Watkins, H, Lecoeur, C, Vollenweider, P, Franco-Cereceda, A, Eriksson, P, Jarvelin, M R R, Stefansson, K, Hamsten, A, Nicholson, G, Karpe, F, Dermitzakis, ET, Lindgren, CM, McCarthy, MI, Froguel, P, Kaakinen, MA, Lyssenko, V, Watanabe, RM, Ingelsson, E, Florez, JC, Dupuis, J, Barroso, I, Morris, AP, and Prokopenko, I
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Published: 2021

5. Genome-wide association studies: the good, the bad and the ugly

Author: Frayling, TM
Published: 2014
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6. Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

Author: Erzurumluoglu, AM, Liu, M, Jackson, VE, Barnes, DR, Datta, G, Melbourne, CA, Young, R, Batini, C, Surendran, P, Jiang, T, Adnan, SD, Afaq, S, Agrawal, A, Altmaier, E, Antoniou, AC, Asselbergs, FW, Baumbach, C, Beirut, L, Bertelsen, S, Boehnke, M, Bots, ML, Brazel, DM, Chambers, JC, Chang-Claude, J, Chen, C, Corley, J, Chou, Y-L, David, SP, de Boer, RA, de Leeuw, CA, Dennis, JG, Dominiczak, AF, Dunning, AM, Easton, DF, Eaton, C, Elliott, P, Evangelou, E, Faul, JD, Foroud, T, Goate, A, Gong, J, Grabe, HJ, Haessler, J, Haiman, C, Hallmans, G, Hammerschlag, AR, Harris, SE, Hattersley, A, Heath, A, Hsu, C, Iacono, WG, Kanoni, S, Kapoor, M, Kaprio, J, Kardia, SL, Karpe, F, Kontto, J, Kooner, JS, Kooperberg, C, Kuulasmaa, K, Laakso, M, Lai, D, Langenberg, C, Le, N, Lettre, G, Loukola, A, Luan, J, Madden, PAF, Mangino, M, Marioni, RE, Marouli, E, Marten, J, Martin, NG, McGue, M, Michailidou, K, Mihailov, E, Moayyeri, A, Moitry, M, Müller-Nurasyid, M, Naheed, A, Nauck, M, Neville, MJ, Nielsen, SF, North, K, Perola, M, Pharoah, PDP, Pistis, G, Polderman, TJ, Posthuma, D, Poulter, N, Qaiser, B, Rasheed, A, Reiner, A, Renström, F, Rice, J, Rohde, R, Rolandsson, O, Samani, NJ, Samuel, M, Schlessinger, D, Scholte, SH, Scott, RA, Sever, P, Shao, Y, Shrine, N, Smith, JA, Starr, JM, Stirrups, K, Stram, D, Stringham, HM, Tachmazidou, I, Tardif, J-C, Thompson, DJ, Tindle, HA, Tragante, V, Trompet, S, Turcot, V, Tyrrell, J, Vaartjes, I, van der Leij, AR, van der Meer, P, Varga, TV, Verweij, N, Völzke, H, Wareham, NJ, Warren, HR, Weir, DR, Weiss, S, Wetherill, L, Yaghootkar, H, Yavas, E, Jiang, Y, Chen, F, Zhan, X, Zhang, W, Zhao, W, Zhou, K, Amouyel, P, Blankenberg, S, Caulfield, MJ, Chowdhury, R, Cucca, F, Deary, IJ, Deloukas, P, Di Angelantonio, E, Ferrario, M, Ferrières, J, Franks, PW, Frayling, TM, Frossard, P, Hall, IP, Hayward, C, Jansson, J-H, Jukema, JW, Kee, F, Männistö, S, Metspalu, A, Munroe, PB, Nordestgaard, BG, Palmer, CNA, Salomaa, V, Sattar, N, Spector, T, Strachan, DP, Understanding Society Scientific Group, EPIC-CVD, GSCAN, Consortium for Genetics of Smoking Behaviour, CHD Exome+ Consortium, van der Harst, P, Zeggini, E, Saleheen, D, Butterworth, AS, Wain, LV, Abecasis, GR, Danesh, J, Tobin, MD, Vrieze, S, Liu, DJ, and Howson, JMM
Abstract: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P
Published: 2020

7. Fetal alleles predisposing to metabolically favourable adiposity are associated with higher birth weight

Author: Thompson, WD, primary, Beaumont, RN, additional, Kuang, A, additional, Warrington, NM, additional, Ji, Y, additional, Tyrrell, J, additional, Wood, AR, additional, Scholtens, D, additional, Knight, BA, additional, Evans, DM, additional, Lowe, WL, additional, Santorelli, G, additional, Azad, R, additional, Mason, D, additional, Hattersley, AT, additional, Frayling, TM, additional, Yaghootkar, H, additional, Borges, MC, additional, Lawlor, DA, additional, and Freathy, RM, additional
Published: 2020
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8. Higher maternal adiposity reduces offspring birth weight if associated with a metabolically favourable profile

Author: Thompson, WD, primary, Beaumont, RN, additional, Kuang, A, additional, Warrington, NM, additional, Ji, Y, additional, Tyrrell, J, additional, Wood, AR, additional, Scholtens, D, additional, Knight, BA, additional, Evans, DM, additional, Lowe, WL, additional, Santorelli, G, additional, Azad, R, additional, Mason, D, additional, Hattersley, AT, additional, Frayling, TM, additional, Yaghootkar, H, additional, Borges, MC, additional, Lawlor, DA, additional, and Freathy, RM, additional
Published: 2020
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9. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author: Couto Alves, A, De Silva, NMG, Karhunen, V, Sovio, U, Das, S, Taal, HR, Warrington, NM, Lewin, AM, Kaakinen, M, Cousminer, DL, Thiering, E, Timpson, NJ, Bond, TA, Lowry, E, Brown, CD, Estivill, X, Lindi, V, Bradfield, JP, Geller, F, Speed, D, Coin, LJM, Loh, M, Barton, SJ, Beilin, LJ, Bisgaard, H, Bønnelykke, K, Alili, R, Hatoum, IJ, Schramm, K, Cartwright, R, Charles, M, Salerno, V, Clément, K, Claringbould, AAJ, BIOS Consortium, van Duijn, CM, Moltchanova, E, Eriksson, JG, Elks, C, Feenstra, B, Flexeder, C, Franks, S, Frayling, TM, Freathy, RM, Elliott, P, Widén, E, Hakonarson, H, Hattersley, AT, Rodriguez, A, Banterle, M, Heinrich, J, Heude, B, Holloway, JW, Hofman, A, Hyppönen, E, Inskip, H, Kaplan, LM, Hedman, AK, Läärä, E, Prokisch, H, Grallert, H, Lakka, TA, Lawlor, DA, Melbye, M, Ahluwalia, TS, Marinelli, M, Millwood, IY, Palmer, LJ, Pennell, CE, Perry, JR, Ring, SM, Savolainen, MJ, Rivadeneira, F, Standl, M, Sunyer, J, Tiesler, CMT, Uitterlinden, AG, Schierding, W, O’Sullivan, JM, Prokopenko, I, Herzig, K, Smith, GD, O'Reilly, P, Felix, JF, Buxton, JL, Blakemore, AIF, Ong, KK, Jaddoe, VWV, Grant, SFA, Sebert, S, McCarthy, MI, Järvelin, M., and Early Growth Genetics (EGG) Consortium
Abstract: Copyright © 2019 The Authors. Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Published: 2019

10. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms

Author: Jones, SE, Lane, JM, Wood, AR, van Hees, VT, Tyrrell, J, Beaumont, RN, Jeffries, AR, Dashti, HS, Hillsdon, M, Ruth, KS, Tuke, MA, Yaghootkar, H, Sharp, SA, Jie, YJ, Thompson, WD, Harrison, JW, Dawes, A, Byrne, EM, Tiemeier, Henning, Allebrandt, KV, Bowden, J, Ray, DW, Freathy, RM, Murray, A, Mazzotti, DR, Gehrman, PR, Lawlor, DA, Frayling, TM, Rutter, MK, Hinds, DA, Saxena, R, Weedon, MN, Agee, M, Alipanahi, B, Auton, A, Bell, RK, Bryc, K, Elson, SL, Fontanillas, P, Furlotte, NA, Huber, KE, Kleinman, A, Litterman, NK, McCreight, JC, McIntyre, MH, Mountain, JL, Noblin, ES, Northover, CAM, Pitts, SJ, Sathirapongsasuti, JF, Sazonova, OV, Shelton, JF, Shringarpure, S, Tian, C, Tung, JY, Vacic, V, Wilson, CH, Epidemiology, and Psychiatry
Published: 2019

11. The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

Author: Middeldorp, CM, Mahajan, A, Horikoshi, M, Robertson, NR, Beaumont, RN, Bradfield, JP, Bustamante, M, Cousminer, DL, Day, FR, De Silva, NM, Guxens, M, Mook-Kanamori, DO, St Pourcain, B, Warrington, NM, Adair, LS, Ahlqvist, E, Ahluwalia, TS, Almgren, P, Ang, W, Atalay, M, Auvinen, J, Bartels, M, Beckmann, JS, Bilbao, JR, Bond, T, Borja, JB, Cavadino, A, Charoen, P, Chen, Z, Coin, L, Cooper, C, Curtin, JA, Custovic, A, Das, S, Davies, GE, Dedoussis, GV, Duijts, L, Eastwood, PR, Eliasen, AU, Elliott, P, Eriksson, JG, Estivill, X, Fadista, J, Fedko, IO, Frayling, TM, Gaillard, R, Gauderman, WJ, Geller, F, Gilliland, F, Gilsanz, V, Granell, R, Grarup, N, Groop, L, Hadley, D, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayes, MG, Hebebrand, J, Heinrich, J, Helgeland, O, Henders, AK, Henderson, J, Henriksen, TB, Hirschhorn, JN, Hivert, M-F, Hocher, B, Holloway, JW, Holt, P, Hottenga, J-J, Hypponen, E, Iniguez, C, Johansson, S, Jugessur, A, Kahonen, M, Kalkwarf, HJ, Kaprio, J, Karhunen, V, Kemp, JP, Kerkhof, M, Koppelman, GH, Korner, A, Kotecha, S, Kreiner-Moller, E, Kulohoma, B, Kumar, A, Kutalik, Z, Lahti, J, Lappe, JM, Larsson, H, Lehtimaki, T, Lewin, AM, Li, J, Lichtenstein, P, Lindgren, CM, Lindi, V, Linneberg, A, Liu, X, Liu, J, Lowe, WL, Lundstrom, S, Lyytikainen, L-P, Ma, RCW, Mace, A, Magi, R, Magnus, P, Mamun, AA, Mannikko, M, Martin, NG, Mbarek, H, McCarthy, NS, Medland, SE, Melbye, M, Melen, E, Mohlke, KL, Monnereau, C, Morgen, CS, Morris, AP, Murray, JC, Myhre, R, Najman, JM, Nivard, MG, Nohr, EA, Nolte, IM, Ntalla, I, O'Reilly, P, Oberfield, SE, Oken, E, Oldehinkel, AJ, Pahkala, K, Palviainen, T, Panoutsopoulou, K, Pedersen, O, Pennell, CE, Pershagen, G, Pitkanen, N, Plomin, R, Power, C, Prasad, RB, Prokopenko, I, Pulkkinen, L, Raikkonen, K, Raitakari, OT, Reynolds, RM, Richmond, RC, Rivadeneira, F, Rodriguez, A, Rose, RJ, Salem, R, Santa-Marina, L, Saw, S-M, Schnurr, TM, Scott, JG, Selzam, S, Shepherd, JA, Simpson, A, Skotte, L, Sleiman, PMA, Snieder, H, Sorensen, TIA, Standl, M, Steegers, EAP, Strachan, DP, Straker, L, Strandberg, T, Taylor, M, Teo, Y-Y, Thiering, E, Torrent, M, Tyrrell, J, Uitterlinden, AG, van Beijsterveldt, T, van der Most, PJ, van Duijn, CM, Viikari, J, Vilor-Tejedor, N, Vogelezang, S, Vonk, JM, Vrijkotte, TGM, Vuoksimaa, E, Wang, CA, Watkins, WJ, Wichmann, H-E, Willemsen, G, Williams, GM, Wilson, JF, Wray, NR, Xu, S, Xu, C-J, Yaghootkar, H, Yi, L, Zafarmand, MH, Zeggini, E, Zemel, BS, Hinney, A, Lakka, TA, Whitehouse, AJO, Sunyer, J, Widen, EE, Feenstra, B, Sebert, S, Jacobsson, B, Njolstad, PR, Stoltenberg, C, Smith, GD, Lawlor, DA, Paternoster, L, Timpson, NJ, Ong, KK, Bisgaard, H, Bonnelykke, K, Jaddoe, VWV, Tiemeier, H, Jarvelin, M-R, Evans, DM, Perry, JRB, Grant, SFA, Boomsma, DI, Freathy, RM, McCarthy, MI, Felix, JF, Middeldorp, CM, Mahajan, A, Horikoshi, M, Robertson, NR, Beaumont, RN, Bradfield, JP, Bustamante, M, Cousminer, DL, Day, FR, De Silva, NM, Guxens, M, Mook-Kanamori, DO, St Pourcain, B, Warrington, NM, Adair, LS, Ahlqvist, E, Ahluwalia, TS, Almgren, P, Ang, W, Atalay, M, Auvinen, J, Bartels, M, Beckmann, JS, Bilbao, JR, Bond, T, Borja, JB, Cavadino, A, Charoen, P, Chen, Z, Coin, L, Cooper, C, Curtin, JA, Custovic, A, Das, S, Davies, GE, Dedoussis, GV, Duijts, L, Eastwood, PR, Eliasen, AU, Elliott, P, Eriksson, JG, Estivill, X, Fadista, J, Fedko, IO, Frayling, TM, Gaillard, R, Gauderman, WJ, Geller, F, Gilliland, F, Gilsanz, V, Granell, R, Grarup, N, Groop, L, Hadley, D, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayes, MG, Hebebrand, J, Heinrich, J, Helgeland, O, Henders, AK, Henderson, J, Henriksen, TB, Hirschhorn, JN, Hivert, M-F, Hocher, B, Holloway, JW, Holt, P, Hottenga, J-J, Hypponen, E, Iniguez, C, Johansson, S, Jugessur, A, Kahonen, M, Kalkwarf, HJ, Kaprio, J, Karhunen, V, Kemp, JP, Kerkhof, M, Koppelman, GH, Korner, A, Kotecha, S, Kreiner-Moller, E, Kulohoma, B, Kumar, A, Kutalik, Z, Lahti, J, Lappe, JM, Larsson, H, Lehtimaki, T, Lewin, AM, Li, J, Lichtenstein, P, Lindgren, CM, Lindi, V, Linneberg, A, Liu, X, Liu, J, Lowe, WL, Lundstrom, S, Lyytikainen, L-P, Ma, RCW, Mace, A, Magi, R, Magnus, P, Mamun, AA, Mannikko, M, Martin, NG, Mbarek, H, McCarthy, NS, Medland, SE, Melbye, M, Melen, E, Mohlke, KL, Monnereau, C, Morgen, CS, Morris, AP, Murray, JC, Myhre, R, Najman, JM, Nivard, MG, Nohr, EA, Nolte, IM, Ntalla, I, O'Reilly, P, Oberfield, SE, Oken, E, Oldehinkel, AJ, Pahkala, K, Palviainen, T, Panoutsopoulou, K, Pedersen, O, Pennell, CE, Pershagen, G, Pitkanen, N, Plomin, R, Power, C, Prasad, RB, Prokopenko, I, Pulkkinen, L, Raikkonen, K, Raitakari, OT, Reynolds, RM, Richmond, RC, Rivadeneira, F, Rodriguez, A, Rose, RJ, Salem, R, Santa-Marina, L, Saw, S-M, Schnurr, TM, Scott, JG, Selzam, S, Shepherd, JA, Simpson, A, Skotte, L, Sleiman, PMA, Snieder, H, Sorensen, TIA, Standl, M, Steegers, EAP, Strachan, DP, Straker, L, Strandberg, T, Taylor, M, Teo, Y-Y, Thiering, E, Torrent, M, Tyrrell, J, Uitterlinden, AG, van Beijsterveldt, T, van der Most, PJ, van Duijn, CM, Viikari, J, Vilor-Tejedor, N, Vogelezang, S, Vonk, JM, Vrijkotte, TGM, Vuoksimaa, E, Wang, CA, Watkins, WJ, Wichmann, H-E, Willemsen, G, Williams, GM, Wilson, JF, Wray, NR, Xu, S, Xu, C-J, Yaghootkar, H, Yi, L, Zafarmand, MH, Zeggini, E, Zemel, BS, Hinney, A, Lakka, TA, Whitehouse, AJO, Sunyer, J, Widen, EE, Feenstra, B, Sebert, S, Jacobsson, B, Njolstad, PR, Stoltenberg, C, Smith, GD, Lawlor, DA, Paternoster, L, Timpson, NJ, Ong, KK, Bisgaard, H, Bonnelykke, K, Jaddoe, VWV, Tiemeier, H, Jarvelin, M-R, Evans, DM, Perry, JRB, Grant, SFA, Boomsma, DI, Freathy, RM, McCarthy, MI, and Felix, JF
Abstract: The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
Published: 2019

12. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

Author: Alves, AC, De Silva, NMG, Karhunen, V, Sovio, U, Das, S, Taal, HR, Warrington, NM, Lewin, AM, Kaakinen, M, Cousminer, DL, Thiering, E, Timpson, NJ, Bond, TA, Lowry, E, Brown, CD, Estivill, X, Lindi, V, Bradfield, JP, Geller, F, Speed, D, Coin, LJM, Loh, M, Barton, SJ, Beilin, LJ, Bisgaard, H, Bonnelykke, K, Alili, R, Hatoum, IJ, Schramm, K, Cartwright, R, Charles, M-A, Salerno, V, Clement, K, Claringbould, AAJ, van Duijn, CM, Moltchanova, E, Eriksson, JG, Elks, C, Feenstra, B, Flexeder, C, Franks, S, Frayling, TM, Freathy, RM, Elliott, P, Widen, E, Hakonarson, H, Hattersley, AT, Rodriguez, A, Banterle, M, Heinrich, J, Heude, B, Holloway, JW, Hofman, A, Hypponen, E, Inskip, H, Kaplan, LM, Hedman, AK, Laara, E, Prokisch, H, Grallert, H, Lakka, TA, Lawlor, DA, Melbye, M, Ahluwalia, TS, Marinelli, M, Millwood, IY, Palmer, LJ, Pennell, CE, Perry, JR, Ring, SM, Savolainen, MJ, Rivadeneira, F, Standl, M, Sunyer, J, Tiesler, CMT, Uitterlinden, AG, Schierding, W, O'Sullivan, JM, Prokopenko, I, Herzig, K-H, Smith, GD, O'Reilly, P, Felix, JF, Buxton, JL, Blakemore, AIF, Ong, KK, Jaddoe, VWV, Grant, SFA, Sebert, S, McCarthy, MI, Jarvelin, M-R, Alves, AC, De Silva, NMG, Karhunen, V, Sovio, U, Das, S, Taal, HR, Warrington, NM, Lewin, AM, Kaakinen, M, Cousminer, DL, Thiering, E, Timpson, NJ, Bond, TA, Lowry, E, Brown, CD, Estivill, X, Lindi, V, Bradfield, JP, Geller, F, Speed, D, Coin, LJM, Loh, M, Barton, SJ, Beilin, LJ, Bisgaard, H, Bonnelykke, K, Alili, R, Hatoum, IJ, Schramm, K, Cartwright, R, Charles, M-A, Salerno, V, Clement, K, Claringbould, AAJ, van Duijn, CM, Moltchanova, E, Eriksson, JG, Elks, C, Feenstra, B, Flexeder, C, Franks, S, Frayling, TM, Freathy, RM, Elliott, P, Widen, E, Hakonarson, H, Hattersley, AT, Rodriguez, A, Banterle, M, Heinrich, J, Heude, B, Holloway, JW, Hofman, A, Hypponen, E, Inskip, H, Kaplan, LM, Hedman, AK, Laara, E, Prokisch, H, Grallert, H, Lakka, TA, Lawlor, DA, Melbye, M, Ahluwalia, TS, Marinelli, M, Millwood, IY, Palmer, LJ, Pennell, CE, Perry, JR, Ring, SM, Savolainen, MJ, Rivadeneira, F, Standl, M, Sunyer, J, Tiesler, CMT, Uitterlinden, AG, Schierding, W, O'Sullivan, JM, Prokopenko, I, Herzig, K-H, Smith, GD, O'Reilly, P, Felix, JF, Buxton, JL, Blakemore, AIF, Ong, KK, Jaddoe, VWV, Grant, SFA, Sebert, S, McCarthy, MI, and Jarvelin, M-R
Abstract: Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
Published: 2019

13. Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour

Author: Jones, SE, van Hees, VT, Mazzotti, DR, Marques-Vidal, P, Sabia, S, van der Spek, Ashley, Dashti, HS, Engmann, J, Kocevska, Desi, Tyrrell, J, Beaumont, RN, Hillsdon, M, Ruth, KS, Tuke, MA, Yaghootkar, H, Sharp, SA, Ji, YJ, Harrison, JW, Freathy, RM, Murray, A, Luik, Annemarie, Amin, Najaf, Lane, JM, Saxena, R, Rutter, MK, Tiemeier, Henning, Kutalik, Z, Kumari, M, Frayling, TM, Weedon, MN, Gehrman, PR, Wood, AR, Jones, SE, van Hees, VT, Mazzotti, DR, Marques-Vidal, P, Sabia, S, van der Spek, Ashley, Dashti, HS, Engmann, J, Kocevska, Desi, Tyrrell, J, Beaumont, RN, Hillsdon, M, Ruth, KS, Tuke, MA, Yaghootkar, H, Sharp, SA, Ji, YJ, Harrison, JW, Freathy, RM, Murray, A, Luik, Annemarie, Amin, Najaf, Lane, JM, Saxena, R, Rutter, MK, Tiemeier, Henning, Kutalik, Z, Kumari, M, Frayling, TM, Weedon, MN, Gehrman, PR, and Wood, AR
Published: 2019

14. Genome-wide association study identifies genetic loci for self-reported habitual sleep duration supported by accelerometer-derived estimates

Author: Dashti, HS, Jones, SE, Wood, AR, Lane, JM, van Hees, VT, Wang, HM, Rhodes, JA, Song, YW, Patel, KN, Anderson, SG, Beaumont, RN, Bechtold, DA, Bowden, J, Cade, BE, Garaulet, M, Kyle, SD, Little, M A, Loudon, AS, Luik, AI, Scheer, F, Spiegelhalder, K, Tyrrell, J, Gottlieb, DJ, Tiemeier, Henning, Ray, DW, Purcell, SM, Frayling, TM, Redline, S, Lawlor, DA, Rutter, MK, Weedon, MN, Saxena, R, Dashti, HS, Jones, SE, Wood, AR, Lane, JM, van Hees, VT, Wang, HM, Rhodes, JA, Song, YW, Patel, KN, Anderson, SG, Beaumont, RN, Bechtold, DA, Bowden, J, Cade, BE, Garaulet, M, Kyle, SD, Little, M A, Loudon, AS, Luik, AI, Scheer, F, Spiegelhalder, K, Tyrrell, J, Gottlieb, DJ, Tiemeier, Henning, Ray, DW, Purcell, SM, Frayling, TM, Redline, S, Lawlor, DA, Rutter, MK, Weedon, MN, and Saxena, R
Published: 2019

15. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 26, 2018)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Di Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Consortium, GG, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

16. Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity (vol 50, pg 765, 2017)

Author: Turcot, V, Lu, Y, Highland, HM, Schurmann, C, Justice, AE, Fine, RS, Bradfield, JP, Esko, T, Giri, A, Graff, M, Guo, X, Hendricks, AE, Karaderi, T, Lempradl, A, Locke, AE, Mahajan, A, Marouli, E, Sivapalaratnam, S, Young, KL, Alfred, T, Feitosa, MF, Masca, NGD, Manning, AK, Medina-Gomez, C, Mudgal, P, Ng, MCY, Reiner, AP, Vedantam, S, Willems, SM, Winkler, TW, Abecasis, G, Aben, KK, Alam, DS, Alharthi, SE, Allison, M, Amouyel, P, Asselbergs, FW, Auer, PL, Balkau, B, Bang, LE, Barroso, I, Bastarache, L, Benn, M, Bergmann, S, Bielak, LF, Bluher, M, Boehnke, M, Boeing, H, Boerwinkle, E, Boger, CA, Bork-Jensen, J, Bots, ML, Bottinger, EP, Bowden, DW, Brandslund, I, Breen, G, Brilliant, MH, Broer, L, Brumat, M, Burt, AA, Butterworth, AS, Campbell, PT, Cappellani, S, Carey, DJ, Catamo, E, Caulfield, MJ, Chambers, JC, Chasman, DI, Chen, Y-DI, Chowdhury, R, Christensen, C, Chu, AY, Cocca, M, Collins, FS, Cook, JP, Corley, J, Galbany, JC, Cox, AJ, Crosslin, DS, Cuellar-Partida, G, D'Eustacchio, A, Danesh, J, Davies, G, Bakker, PIW, Groot, MCH, Mutsert, R, Deary, IJ, Dedoussis, G, Demerath, EW, Heijer, M, Hollander, AI, Ruijter, HM, Dennis, JG, Denny, JC, Angelantonio, E, Drenos, F, Du, M, Dube, M-P, Dunning, AM, Easton, DF, Edwards, TL, Ellinghaus, D, Ellinor, PT, Elliott, P, Evangelou, E, Farmaki, A-E, Farooqi, IS, Faul, JD, Fauser, S, Feng, S, Ferrannini, E, Ferrieres, J, Florez, JC, Ford, I, Fornage, M, Franco, OH, Franke, A, Franks, PW, Friedrich, N, Frikke-Schmidt, R, Galesloot, TE, Gan, W, Gandin, I, Gasparini, P, Gibson, J, Giedraitis, V, Gjesing, AP, Gordon-Larsen, P, Gorski, M, Grabe, H-J, Grant, SFA, Grarup, N, Griffiths, HL, Grove, ML, Gudnason, V, Gustafsson, S, Haessler, J, Hakonarson, H, Hammerschlag, AR, Hansen, T, Harris, KM, Harris, TB, Hattersley, AT, Have, CT, Hayward, C, He, L, Heard-Costa, NL, Heath, AC, Heid, IM, Helgeland, O, Hernesniemi, J, Hewitt, AW, Holmen, OL, Hovingh, GK, Howson, JMM, Hu, Y, Huang, PL, Huffman, JE, Ikram, MA, Ingelsson, E, Jackson, AU, Jansson, J-H, Jarvik, GP, Jensen, GB, Jia, Y, Johansson, S, Jorgensen, ME, Jorgensen, T, Jukema, JW, Kahali, B, Kahn, RS, Kahonen, M, Kamstrup, PR, Kanoni, S, Kaprio, J, Karaleftheri, M, Kardia, SLR, Karpe, F, Kathiresan, S, Kee, F, Kiemeney, LA, Kim, E, Kitajima, H, Komulainen, P, Kooner, JS, Kooperberg, C, Korhonen, T, Kovacs, P, Kuivaniemi, H, Kutalik, Z, Kuulasmaa, K, Kuusisto, J, Laakso, M, Lakka, TA, Lamparter, D, Lange, EM, Lange, LA, Langenberg, C, Larson, EB, Lee, NR, Lehtimaki, T, Lewis, CE, Li, H, Li, J, Li-Gao, R, Lin, H, Lin, K-H, Lin, L-A, Lin, X, Lind, L, Lindstrom, J, Linneberg, A, Liu, C-T, Liu, DJ, Liu, Y, Lo, KS, Lophatananon, A, Lotery, AJ, Loukola, A, Luan, J, Lubitz, SA, Lyytikainen, L-P, Mannisto, S, Marenne, G, Mazul, AL, McCarthy, MI, McKean-Cowdin, R, Medland, SE, Meidtner, K, Milani, L, Mistry, V, Mitchell, P, Mohlke, KL, Moilanen, L, Moitry, M, Montgomery, GW, Mook-Kanamori, DO, Moore, C, Mori, TA, Morris, AD, Morris, AP, Mueller-Nurasyid, M, Munroe, PB, Nalls, MA, Narisu, N, Nelson, CP, Neville, M, Nielsen, SF, Nikus, K, Njolstad, PR, Nordestgaard, BG, Nyholt, DR, O'Connel, JR, O'Donoghue, ML, Loohuis, LMO, Ophoff, RA, Owen, KR, Packard, CJ, Padmanabhan, S, Palmer, CNA, Palmer, ND, Pasterkamp, G, Patel, AP, Pattie, A, Pedersen, O, Peissig, PL, Peloso, GM, Pennell, CE, Perola, M, Perry, JA, Perry, JRB, Pers, TH, Person, TN, Peters, A, Petersen, ERB, Peyser, PA, Pirie, A, Polasek, O, Polderman, TJ, Puolijoki, H, Raitakari, OT, Rasheed, A, Rauramaa, R, Reilly, DF, Renstrom, F, Rheinberger, M, Ridker, PM, Rioux, JD, Rivas, MA, Roberts, DJ, Robertson, NR, Robino, A, Rolandsson, O, Rudan, I, Ruth, KS, Saleheen, D, Salomaa, V, Samani, NJ, Sapkota, Y, Sattar, N, Schoen, RE, Schreiner, PJ, Schulze, MB, Scott, RA, Segura-Lepe, MP, Shah, SH, Sheu, WH-H, Sim, X, Slater, AJ, Small, KS, Smith, AV, Southam, L, Spector, TD, Speliotes, EK, Starr, JM, Stefansson, K, Steinthorsdottir, V, Stirrups, KE, Strauch, K, Stringham, HM, Stumvoll, M, Sun, L, Surendran, P, Swift, AJ, Tada, H, Tansey, KE, Tardif, J-C, Taylor, KD, Teumer, A, Thompson, DJ, Thorleifsson, G, Thorsteinsdottir, U, Thuesen, BH, Tonjes, A, Tromp, G, Trompet, S, Tsafantakis, E, Tuomilehto, J, Tybjaerg-Hansen, A, Tyrer, JP, Uher, R, Uitterlinden, AG, Uusitupa, M, Laan, SW, Duijn, CM, Leeuwen, N, van Setten, J, Vanhala, M, Varbo, A, Varga, TV, Varma, R, Edwards, DRV, Vermeulen, SH, Veronesi, G, Vestergaard, H, Vitart, V, Vogt, TF, Volker, U, Vuckovic, D, Wagenknecht, LE, Walker, M, Wallentin, L, Wang, F, Wang, CA, Wang, S, Wang, Y, Ware, EB, Wareham, NJ, Warren, HR, Waterworth, DM, Wessel, J, White, HD, Willer, CJ, Wilson, JG, Witte, DR, Wood, AR, Wu, Y, Yaghootkar, H, Yao, J, Yao, P, Yerges-Armstrong, LM, Young, R, Zeggini, E, Zhan, X, Zhang, W, Zhao, JH, Zhao, W, Zhou, W, Zondervan, KT, Rotter, JI, Pospisilik, JA, Rivadeneira, F, Borecki, IB, Deloukas, P, Frayling, TM, Lettre, G, North, KE, Lindgren, CM, Hirschhorn, JN, Loos, RJF, Graduate School, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
Published: 2018

17. Erratum: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.

Author: Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, van de Bunt, M, Pearson, RD, Kumar, A, Mueller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, de Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RCW, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, McCarthy, MI, Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, van de Bunt, M, Pearson, RD, Kumar, A, Mueller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, de Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RCW, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, and McCarthy, MI
Abstract: This corrects the article DOI: 10.1038/sdata.2017.179.
Published: 2018

18. Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics

Author: Beaumont, RN, Warrington, NM, Cavadino, A, Tyrrell, J, Nodzenski, M, Horikoshi, M, Geller, F, Myhre, R, Richmond, Rebecca, Paternoster, L, Bradfield, JP, Kreiner-Moller, E, Huikari, V, Metrustry, S, Lunetta, KL, Painter, JN, Hottenga, JJ, Allard, C, Barton, SJ, Espinosa, A, Marsh, JA, Potter, C, Zhang, G, Ang, W, Berry, DJ, Bouchard, L, Das, S, Hakonarson, H, Heikkinen, J, Helgeland, O, Hocher, B, Hofman, Bert, Inskip, HM, Jones, SE, Kogevinas, M, Lind, PA, Marullo, L, Medland, SE, Murray, A, Murray, JC, Njolstad, PR, Nohr, EA, Reichetzeder, C, Ring, SM, Ruth, KS, Santa-Marina, L, Scholtens, DM, Sebert, S, Sengpiel, V, Tuke, MA, Vaudel, M, Weedon, MN, Willemsen, G, Wood, AR, Yaghootkar, H, Muglia, LJ, Bartels, M, Relton, CL, Pennell, CE, Chatzi, L, Estivill, X, Holloway, JW, Boomsma, DI, Montgomery, GW, Murabito, JM, Spector, TD, Power, C, Jarvelin, MR, Bisgaard, H, Grant, SFA, Sorensen, TIA, Jaddoe, Vincent, Jacobsson, B, Melbye, M, McCarthy, MI, Hattersley, AT, Hayes, MG, Frayling, TM, Hivert, MF, Felix, Janine, Hypponen, E, Lowe, WL, Evans, DM, Lawlor, DA, Feenstra, B, Freathy, RM, Beaumont, RN, Warrington, NM, Cavadino, A, Tyrrell, J, Nodzenski, M, Horikoshi, M, Geller, F, Myhre, R, Richmond, Rebecca, Paternoster, L, Bradfield, JP, Kreiner-Moller, E, Huikari, V, Metrustry, S, Lunetta, KL, Painter, JN, Hottenga, JJ, Allard, C, Barton, SJ, Espinosa, A, Marsh, JA, Potter, C, Zhang, G, Ang, W, Berry, DJ, Bouchard, L, Das, S, Hakonarson, H, Heikkinen, J, Helgeland, O, Hocher, B, Hofman, Bert, Inskip, HM, Jones, SE, Kogevinas, M, Lind, PA, Marullo, L, Medland, SE, Murray, A, Murray, JC, Njolstad, PR, Nohr, EA, Reichetzeder, C, Ring, SM, Ruth, KS, Santa-Marina, L, Scholtens, DM, Sebert, S, Sengpiel, V, Tuke, MA, Vaudel, M, Weedon, MN, Willemsen, G, Wood, AR, Yaghootkar, H, Muglia, LJ, Bartels, M, Relton, CL, Pennell, CE, Chatzi, L, Estivill, X, Holloway, JW, Boomsma, DI, Montgomery, GW, Murabito, JM, Spector, TD, Power, C, Jarvelin, MR, Bisgaard, H, Grant, SFA, Sorensen, TIA, Jaddoe, Vincent, Jacobsson, B, Melbye, M, McCarthy, MI, Hattersley, AT, Hayes, MG, Frayling, TM, Hivert, MF, Felix, Janine, Hypponen, E, Lowe, WL, Evans, DM, Lawlor, DA, Feenstra, B, and Freathy, RM
Published: 2018

19. Data Descriptor: Sequence data and association statistics from 12,940 type 2 diabetes cases and controls

Author: Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, De Bunt, MV, Pearson, RD, Kumar, A, Muller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, De Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RC, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, McCarthy, MI, Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, McCarthy, DJ, Rivas, MA, Perry, JRB, Sim, X, Blackwell, TW, Robertson, NR, Rayner, NW, Cingolani, P, Locke, AE, Tajes, JF, Highland, HM, Dupuis, J, Chines, PS, Lindgren, CM, Hartl, C, Jackson, AU, Chen, H, Huyghe, JR, De Bunt, MV, Pearson, RD, Kumar, A, Muller-Nurasyid, M, Grarup, N, Stringham, HM, Gamazon, ER, Lee, J, Chen, Y, Scott, RA, Below, JE, Chen, P, Huang, J, Go, MJ, Stitzel, ML, Pasko, D, Parker, SCJ, Varga, TV, Green, T, Beer, NL, Day-Williams, AG, Ferreira, T, Fingerlin, T, Horikoshi, M, Hu, C, Huh, I, Ikram, MK, Kim, B-J, Kim, Y, Kim, YJ, Kwon, M-S, Lee, S, Lin, K-H, Maxwell, TJ, Nagai, Y, Wang, X, Welch, RP, Yoon, J, Zhang, W, Barzilai, N, Voight, BF, Han, B-G, Jenkinson, CP, Kuulasmaa, T, Kuusisto, J, Manning, A, Ng, MCY, Palmer, ND, Balkau, B, Stancakova, A, Abboud, HE, Boeing, H, Giedraitis, V, Prabhakaran, D, Gottesman, O, Scott, J, Carey, J, Kwan, P, Grant, G, Smith, JD, Neale, BM, Purcell, S, Butterworth, AS, Howson, JMM, Lee, HM, Lu, Y, Kwak, S-H, Zhao, W, Danesh, J, Lam, VKL, Park, KS, Saleheen, D, So, WY, Tam, CHT, Afzal, U, Aguilar, D, Arya, R, Aung, T, Chan, E, Navarro, C, Cheng, C-Y, Palli, D, Correa, A, Curran, JE, Rybin, D, Farook, VS, Fowler, SP, Freedman, BI, Griswold, M, Hale, DE, Hicks, PJ, Khor, C-C, Kumar, S, Lehne, B, Thuillier, D, Lim, WY, Liu, J, Loh, M, Musani, SK, Puppala, S, Scott, WR, Yengo, L, Tan, S-T, Taylor, HA, Thameem, F, Wilson, G, Wong, TY, Njolstad, PR, Levy, JC, Mangino, M, Bonnycastle, LL, Schwarzmayr, T, Fadista, J, Surdulescu, GL, Herder, C, Groves, CJ, Wieland, T, Bork-Jensen, J, Brandslund, I, Christensen, C, Koistinen, HA, Doney, ASF, Kinnunen, L, Esko, T, Farmer, AJ, Hakaste, L, Hodgkiss, D, Kravic, J, Lyssenko, V, Hollensted, M, Jorgensen, ME, Jorgensen, T, Ladenvall, C, Justesen, JM, Karajamaki, A, Kriebel, J, Rathmann, W, Lannfelt, L, Lauritzen, T, Narisu, N, Linneberg, A, Melander, O, Milani, L, Neville, M, Orho-Melander, M, Qi, L, Qi, Q, Roden, M, Rolandsson, O, Swift, A, Rosengren, AH, Stirrups, K, Wood, AR, Mihailov, E, Blancher, C, Carneiro, MO, Maguire, J, Poplin, R, Shakir, K, Fennell, T, DePristo, M, De Angelis, MH, Deloukas, P, Gjesing, AP, Jun, G, Nilsson, PM, Murphy, J, Onofrio, R, Thorand, B, Hansen, T, Meisinger, C, Hu, FB, Isomaa, B, Karpe, F, Liang, L, Peters, A, Huth, C, O'Rahilly, SP, Palmer, CNA, Pedersen, O, Rauramaa, R, Tuomilehto, J, Salomaa, V, Watanabe, RM, Syvanen, A-C, Bergman, RN, Bharadwaj, D, Bottinger, EP, Cho, YS, Chandak, GR, Chan, JC, Chia, KS, Daly, MJ, Ebrahim, SB, Langenberg, C, Elliott, P, Jablonski, KA, Lehman, DM, Jia, W, Ma, RC, Pollin, TI, Sandhu, M, Tandon, N, Froguel, P, Barroso, I, Teo, YY, Zeggini, E, Loos, RJF, Small, KS, Ried, JS, DeFronzo, RA, Grallert, H, Glaser, B, Metspalu, A, Wareham, NJ, Walker, M, Banks, E, Gieger, C, Ingelsson, E, Im, HK, Illig, T, Franks, PW, Buck, G, Trakalo, J, Buck, D, Prokopenko, I, Magi, R, Lind, L, Farjoun, Y, Owen, KR, Gloyn, AL, Strauch, K, Tuomi, T, Kooner, JS, Lee, J-Y, Park, T, Donnelly, P, Morris, AD, Hattersley, AT, Bowden, DW, Collins, FS, Atzmon, G, Chambers, JC, Spector, TD, Laakso, M, Strom, TM, Bell, GI, Blangero, J, Duggirala, R, Tai, E, McVean, G, Hanis, CL, Wilson, JG, Seielstad, M, Frayling, TM, Meigs, JB, Cox, NJ, Sladek, R, Lander, ES, Gabriel, S, Mohlke, KL, Meitinger, T, Groop, L, Abecasis, G, Scott, LJ, Morris, AP, Kang, HM, Altshuler, D, Burtt, NP, Florez, JC, Boehnke, M, and McCarthy, MI
Abstract: To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
Published: 2017

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

Author: Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, LT, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, QB, Ngwa, JS, Renstrom, F, Quaye, L, Eicher, JD, Hayes, J E, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, WH, Zhao, W, Griffin, PJ, Haller, T, Ahmad, Shahzad, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikainen, LP, Huppertz, C, Willemsen, G, Peyrot, WJ, Wu, Fenny, Kristiansson, K, Demirkan, Ayse, Fornage, M, Hassinen, M, Bielak, LF, Cadby, G, Tanaka, T, Magl, R, van der Most, PJ, Jackson, AU, Bragg-Gresham, JL, Vitart, V, Marten, J, Navarro, P, Bellis, C, Pasko, D, Johansson, A, Snitker, S, Cheng, YC, Eriksson, J, Lim, U, Aadahl, M, Adair, LS, Amin, Najaf, Balkau, B, Auvinen, J, Beilby, J, Bergman, RN, Bergmann, S, Bertoni, AG, Blangero, J, Bonnefond, A, Bonnycastle, LL, Borja, JB, Brage, S, Busonero, F, Buyske, S, Campbell, H, Chines, PS, Collins, FS, Corre, T, Smith, GD, Delgado, GE, Dueker, N, Dorr, M, Ebeling, T, Eiriksdottir, G, Esko, T, Faul, JD, Fu, M, Faerch, K, Gieger, C, Glaser, S, Gong, J, Gordon-Larsen, P, Grallert, H, Grammer, TB, Grarup, N, Van Grootheest, G, Harald, K, Hastie, ND, Havulinna, AS, Hernandez, D, Hindorff, L, Hocking, LJ, Holmens, OL, Holzapfel, C, Hottenga, JJ, Huang, J, Huang, T, Hui, J, Huth, C, Hutri-Kahonen, N, James, AL, Jansson, JO, Jhun, MA, Juonala, M, Kinnunen, L, Koistinen, HA, Kolcic, I, Komulainen, P, Kuusisto, J, Kvaloy, K, Kahonen, M, Lakka, TA, Launer, LJ, Lehne, B, Lindgren, CM, Lorentzon, M, Luben, R, Marre, M (Michel), Milaneschi, Y, Monda, KL, Montgomery, GW, de Moor, MHM, Mulas, A, Muller-Nurasyid, M, Musk, AW, Mannikko, R, Mannisto, S, Narisu, N, Nauck, M, Nettleton, JA, Nolte, IM, Oldehinkel, AJ (A.), Olden, M, Ong, KK, Padmanabhan, S, Paternoster, L, Perez, J, Perola, M, Peters, A, Peters, U, Peyser, PA, Prokopenko, I, Puolijoki, H, Raitakari, OT, Rankinen, T, Rasmussen-Torvik, LJ, Rawal, R, Ridker, PM, Rose, LM, Rudan, I, Sarti, C, Sarzynski, MA, Savonen, K, Scott, WR, Sanna, S, Shuldiner, AR, Sidney, S, Silbernagel, G, Smith, BH, Smith, JA, Snieder, H, Stancakova, A, Sternfeld, B, Swift, AJ, Tammelin, T, Tan, ST, Thorand, B, Thuillier, D, Vandenput, L, Vestergaard, H, van Vliet-Ostaptchouk, JV, Vohl, MC, Volker, U, Waeber, G, Walker, M, Wild, S, Wong, A, Wright, AF, Zillikens, M.C., Zubair, N, Haiman, CA, LeMarchand, L, Gyllensten, U, Ohlsson, C, Ohlsson, CC, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Perusse, L, Wilson, JF, Hayward, C, Polasek, O, Cucca, F, Hveem, K, Hartman, CA, Tonjes, A, Bandinelli, S, Palmer, LJ, Kardia, SLR, Rauramaa, R, Sorensen, TIA, Tuomilehto, J, Salomaa, V, Penninx, B, de Geus, EJC, Boomsma, DI, Lehtimaki, T, Mangino, M, Laakso, M, Bouchard, C, Martin, NG, Kuh, D, Liu, YM, Linneberg, A, Marz, W, Strauch, K, Kivimaki, M, Harris, TB, Gudnason, V, Volzke, H, Qi, L, Jarvelin, MR, Chambers, JC, Kooner, JS, Froguel, P, Kooperberg, C, Vollenweider, P, Hallmans, G, Hansen, T, Pedersen, O, Metspalu, A, Wareham, NJ, Langenberg, C, Weir, DR, Porteous, DJ, Boerwinkle, E, Chasman, DI, Abecasis, GR, Barroso, I, McCarthy, MI, Frayling, TM, O'Connell, JR, Duijn, Cornelia, Boehnke, M, Heid, IM, Mohlke, KL, Strachan, DP, Fox, CS, Liu, CT, Hirschhorn, JN, Klein, RJ, Johnson, AD, Borecki, IB, Franks, PW, North, KE, Cupples, LA, Loos, RJF, Kilpelainen, TO, Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, LT, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, QB, Ngwa, JS, Renstrom, F, Quaye, L, Eicher, JD, Hayes, J E, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, WH, Zhao, W, Griffin, PJ, Haller, T, Ahmad, Shahzad, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikainen, LP, Huppertz, C, Willemsen, G, Peyrot, WJ, Wu, Fenny, Kristiansson, K, Demirkan, Ayse, Fornage, M, Hassinen, M, Bielak, LF, Cadby, G, Tanaka, T, Magl, R, van der Most, PJ, Jackson, AU, Bragg-Gresham, JL, Vitart, V, Marten, J, Navarro, P, Bellis, C, Pasko, D, Johansson, A, Snitker, S, Cheng, YC, Eriksson, J, Lim, U, Aadahl, M, Adair, LS, Amin, Najaf, Balkau, B, Auvinen, J, Beilby, J, Bergman, RN, Bergmann, S, Bertoni, AG, Blangero, J, Bonnefond, A, Bonnycastle, LL, Borja, JB, Brage, S, Busonero, F, Buyske, S, Campbell, H, Chines, PS, Collins, FS, Corre, T, Smith, GD, Delgado, GE, Dueker, N, Dorr, M, Ebeling, T, Eiriksdottir, G, Esko, T, Faul, JD, Fu, M, Faerch, K, Gieger, C, Glaser, S, Gong, J, Gordon-Larsen, P, Grallert, H, Grammer, TB, Grarup, N, Van Grootheest, G, Harald, K, Hastie, ND, Havulinna, AS, Hernandez, D, Hindorff, L, Hocking, LJ, Holmens, OL, Holzapfel, C, Hottenga, JJ, Huang, J, Huang, T, Hui, J, Huth, C, Hutri-Kahonen, N, James, AL, Jansson, JO, Jhun, MA, Juonala, M, Kinnunen, L, Koistinen, HA, Kolcic, I, Komulainen, P, Kuusisto, J, Kvaloy, K, Kahonen, M, Lakka, TA, Launer, LJ, Lehne, B, Lindgren, CM, Lorentzon, M, Luben, R, Marre, M (Michel), Milaneschi, Y, Monda, KL, Montgomery, GW, de Moor, MHM, Mulas, A, Muller-Nurasyid, M, Musk, AW, Mannikko, R, Mannisto, S, Narisu, N, Nauck, M, Nettleton, JA, Nolte, IM, Oldehinkel, AJ (A.), Olden, M, Ong, KK, Padmanabhan, S, Paternoster, L, Perez, J, Perola, M, Peters, A, Peters, U, Peyser, PA, Prokopenko, I, Puolijoki, H, Raitakari, OT, Rankinen, T, Rasmussen-Torvik, LJ, Rawal, R, Ridker, PM, Rose, LM, Rudan, I, Sarti, C, Sarzynski, MA, Savonen, K, Scott, WR, Sanna, S, Shuldiner, AR, Sidney, S, Silbernagel, G, Smith, BH, Smith, JA, Snieder, H, Stancakova, A, Sternfeld, B, Swift, AJ, Tammelin, T, Tan, ST, Thorand, B, Thuillier, D, Vandenput, L, Vestergaard, H, van Vliet-Ostaptchouk, JV, Vohl, MC, Volker, U, Waeber, G, Walker, M, Wild, S, Wong, A, Wright, AF, Zillikens, M.C., Zubair, N, Haiman, CA, LeMarchand, L, Gyllensten, U, Ohlsson, C, Ohlsson, CC, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Perusse, L, Wilson, JF, Hayward, C, Polasek, O, Cucca, F, Hveem, K, Hartman, CA, Tonjes, A, Bandinelli, S, Palmer, LJ, Kardia, SLR, Rauramaa, R, Sorensen, TIA, Tuomilehto, J, Salomaa, V, Penninx, B, de Geus, EJC, Boomsma, DI, Lehtimaki, T, Mangino, M, Laakso, M, Bouchard, C, Martin, NG, Kuh, D, Liu, YM, Linneberg, A, Marz, W, Strauch, K, Kivimaki, M, Harris, TB, Gudnason, V, Volzke, H, Qi, L, Jarvelin, MR, Chambers, JC, Kooner, JS, Froguel, P, Kooperberg, C, Vollenweider, P, Hallmans, G, Hansen, T, Pedersen, O, Metspalu, A, Wareham, NJ, Langenberg, C, Weir, DR, Porteous, DJ, Boerwinkle, E, Chasman, DI, Abecasis, GR, Barroso, I, McCarthy, MI, Frayling, TM, O'Connell, JR, Duijn, Cornelia, Boehnke, M, Heid, IM, Mohlke, KL, Strachan, DP, Fox, CS, Liu, CT, Hirschhorn, JN, Klein, RJ, Johnson, AD, Borecki, IB, Franks, PW, North, KE, Cupples, LA, Loos, RJF, and Kilpelainen, TO
Published: 2017

21. Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Author: Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, Cupples, LA, Justice, AE, Winkler, TW, Feitosa, MF, Graff, M, Fisher, V A, Young, K, Barata, L, Deng, X, Czajkowski, J, Hadley, D, Ngwa, JS, Ahluwalia, TS, Chu, AY, Heard-Costa, NL, Lim, E, Perez, J, Eicher, JD, Kutalik, Z, Xue, L, Mahajan, A, Renstrom, F, Wu, J, Qi, QB, Ahmad, Shahzad, Alfred, T, Amin, Najaf, Bielak, LF, Bonnefond, A, Bragg, J, Cadby, G, Chittani, M, Coggeshall, S, Corre, T, Direk, N, Eriksson, J, Fischer, K, Gorski, M, Harder, MN, Horikoshi, M, Huang, T, Huffman, JE, Jackson, AU, Justesen, JM, Kanoni, S, Kinnunen, L, Kleber, ME, Komulainen, P, Kumari, M, Lim, U, Luan, J, Lyytikainen, LP, Mangino, M, Manichaikul, A, Marten, J, Middelberg, RPS, Mueller-Nurasyid, M, Navarro, P, Perusse, L, Pervjakova, N, Sarti, C, Smith, AV, Smith, JA, Stancakova, A, Strawbridge, RJ, Stringham, HM, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van der Most, PJ, van Vliet-Ostaptchouk, JV, Vedantam, SL, Verweij, N (Niek), Vink, JM, Vitart, V, Wu, Fenny, Yengo, L, Zhang, WH, Zhao, JH, Zimmermann, ME, Zubair, N, Abecasis, GR, Adair, LS, Afaq, S, Afzal, U, Bakker, SJL, Bartz, TM, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boerwinkle, E, Bonnycastle, LL, Bottinger, E, Braga, D, Buckley, BM, Buyske, S, Campbell, H, Chambers, JC, Collins, FS, Curran, JE, de Borst, GJ, de Craen, AJM, de Geus, EJC, Dedoussis, G, Delgado, GE, den Ruijter, HM, Eiriksdottir, G, Eriksson, AL, Esko, T, Faul, JD, Ford, I, Forrester, T, Gertow, K, Gigante, B, Glorioso, N, Gong, J, Grallert, H, Grammer, TB, Grarup, N, Haitjema, S, Hallmans, G, Hamsten, A, Hansen, T, Harris, TB, Hartman, CA, Hassinen, M, Hastie, ND, Heath, AC, Hernandez, D, Hindorff, L, Hocking, LJ, Hollensted, M, Holmen, OL, Homuth, G, Hottenga, JJ, Huang, J, Hung, J, Hutri-Kahonen, N, Ingelsson, E, James, AL, Jansson, JO, Jarvelin, MR, Jhun, MA, Jorgensen, ME, Juonala, M, Kahonen, M, Karlsson, M, Koistinen, HA, Kolcic, I, Kolovou, G, Kooperberg, C, Kramer, BK, Kuusisto, J, Kvaloy, K, Lakka, TA, Langenberg, C, Launer, LJ, Leander, K, Lee, NR, Lind, L, Lindgren, CM, Linneberg, A, Lobbens, S, Loh, M, Lorentzon, M, Luben, R, Lubke, G, Ludolph-Donislawski, A, Lupoli, S, Madden, PAF, Mannikko, R, Marques-Vidal, P, Martin, NG, McKenzie, CA, McKnight, B, Mellstrom, D, Menni, C, Montgomery, GW, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Peyser, PA, Pisinger, C, Porteous, DJ, Raitakari, OT, Rankinen, T, Rao, DC, Rasmussen-Torvik, LJ, Rawal, R, Rice, T, Ridker, PM, Rose, LM, Bien, SA, Rudan, I, Sanna, S, Sarzynski, MA, Sattar, N, Savonen, K, Schlessinger, D, Scholtens, s, Schurmann, C, Scott, RA, Sennblad, B, Siemelink, MA, Silbernagel, G, Slagboom, PE (Eline), Snieder, H, Staessen, JA, Stott, DJ, Swertz, MA, Swift, AJ, Taylor, KD, Tayo, BO, Thorand, B, Thuillier, D, Tuomilehto, J, Uitterlinden, André, Vandenput, L, Vohl, MC, Volzke, H, Vonk, JM, Waeber, G, Waldenberger, M, Westendorp, RGJ, Wild, S, Willemsen, G, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zhao, W, Zillikens, M.C., Baldassarre, D, Balkau, B, Bandinelli, S, Boger, CA, Boomsma, DI, Bouchard, C, Bruinenberg, M, Chasman, DI, Chen, YDI, Chines, PS, Cooper, RS, Cucca, F, Cusi, D, de Faire, U, Ferrucci, L, Franks, PW, Froguel, P, Gordon-Larsen, P, Grabe, HJ, Gudnason, V, Haiman, CA, Hayward, C, Hveem, K, Johnson, AD, Jukema, W, Kardia, SLR, Kivimaki, M, Kooner, JS, Kuh, D, Laakso, M, Lehtimaki, T, Le Marchand, L, Marz, W, McCarthy, MI, Metspalu, A, Morris, AP, Ohlsson, C, Palmer, LJ, Pasterkamp, G, Pedersen, O, Peters, A, Peters, U, Polasek, O, Psaty, BM, Qi, L, Rauramaa, R, Smith, BH, Sorensen, TIA, Strauch, K, Tiemeier, Henning, Tremoli, E, van der Harst, P, Vestergaard, H, Vollenweider, P, Wareham, NJ, Weir, DR, Whitfield, JB, Wilson, JF, Tyrrell, J, Frayling, TM, Barroso, I, Boehnke, M, Deloukas, P, Fox, CS, Hirschhorn, JN, Hunter, DJ, Spector, TD, Strachan, DP, Duijn, Cornelia, Heid, IM, Mohlke, KL, Marchini, J, Loos, RJF, Kilpelainen, TO, Liu, CT, Borecki, IB, North, KE, and Cupples, LA
Published: 2017

22. Trans-ethnic meta-analysis of white blood cell phenotypes

Author: Keller, Margaux F, Reiner, Alexander P, Okada, Yukinori, van Rooij, Frank J. A, Johnson, Andrew D, Chen, Ming Huei, Smith, Albert V, Morris, Andrew P, Tanaka, Toshiko, Ferrucci, Luigi, Zonderman, Alan B, Lettre, Guillaume, Harris, Tamara, Garcia, Melissa, Bandinelli, Stefania, Qayyum, Rehan, Yanek, Lisa R, Becker, Diane M, Becker, Lewis C, Kooperberg, Charles, Keating, Brendan, Reis, Jared, Tang, Hua, Boerwinkle, Eric, Kamatani, Yoichiro, Matsuda, Koichi, Kamatani, Naoyuki, Nakamura, Yusuke, Kubo, Michiaki, Liu, Simin, Dehghan, Abbas, Felix, Janine F, Hofman, Albert, Uitterlinden, André G, van Duijn, Cornelia M, Franco, Oscar H, Longo, Dan L, Singleton, Andrew B, Psaty, Bruce M, Evans, Michelle K, Cupples, L. Adrienne, Rotter, Jerome I, O'Donnell, Christopher J, Takahashi, Atsushi, Wilson, James G, Ganesh, Santhi K, Nalls, Mike A, Arepalli, S, Bandinelli, S, Biffi, A, Bis, Jc, Boerwinkle, E, Chakravarti, A, Chen, Mh, Chong, S, Coresh, J, Couper, Dj, Cupples, L, Dehghan, A, Do'Ring, A, Eiriksdottir, G, Felix, Jf, Ferrucci, L, Folsom, Ar, Fox, Cs, Frayling, Tm, Ganesh, Sk, Garcia, M, Garner, Sf, Gasparini, Paolo, Gieger, C, Glazer, Nl, Gouskova, Na, Greinacher, A, Gudnason, V, Harris, Tb, Hernandez, Dg, Hofman, A, Illig, T, Kamatani, Y, Kamatani, N, Kubo, M, Kuhnel, B, Lagou, V, Lettre, G, Levi, D, Lin, J, Liu, Y, Longo, Dl, Lumley, T, Mangino, M, Matsuda, K, Meisinger, C, Melzer, D, Menzel, S, Moore, M, Nakamura, Y, Nalls, Ma, Nauck, M, O'Donnell, Cj, Okada, Y, Oostra, Ba, Ouwehand, Wh, Patel, Kv, Pirastu, Nicola, Pistis, Giorgio, Prokisch, H, Prokopenko, I, Psaty, Bm, Reiner, Ap, Rendon, A, Sambrook, J, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stephens, J, Stumvoll, M, Takahashi, A, Tanaka, T, Taylor, K, Teumer, A, Thein, Sl, To'Njes, A, Toniolo, D, Tsunoda, T, Uitterlinden, Ag, van Duijn CM, van Rooij FJ, Vo'Lker, U, Vo'Lzke, H, Wichmann, H., Wiggins, Kl, Wilson, Jg, Witteman, Jc, Wood, Ar, Yamamoto, K, Yang, Q, Zakai, Na, Austin, Ma, Becker, Dm, Britton, A, Chen, Z, Couper, D, Curb, J, Dean, E, Eaton, Cb, Evans, Mk, Fornage, M, Grant, Sf, Hernandez, D, Kamatini, N, Keating, Bj, Lacroix, A, Lange, La, Liu, S, Lohman, K, Mathias, R, Meng, Y, Mohler ER 3rd, Musani, S, Palmer, Cd, Papanicolaou, Gj, Snively, Bm, Tang, H, Taylor HA Jr, Thomson, C, Yanek, Lr, Yang, L, Ziv, E, Zonderman, Ab, Higasa, K, Hirota, T, Hosono, N, Kumasaka, N, Ohmiya, H, Tamari, M, Yamaguchi Kabata, Y, Yamamoto, K., Epidemiology, Medical Informatics, Urology, Erasmus MC other, Internal Medicine, Keller, Margaux F, Reiner, Alexander P, Okada, Yukinori, van Rooij, Frank J. A, Johnson, Andrew D, Chen, Ming Huei, Smith, Albert V, Morris, Andrew P, Tanaka, Toshiko, Ferrucci, Luigi, Zonderman, Alan B, Lettre, Guillaume, Harris, Tamara, Garcia, Melissa, Bandinelli, Stefania, Qayyum, Rehan, Yanek, Lisa R, Becker, Diane M, Becker, Lewis C, Kooperberg, Charle, Keating, Brendan, Reis, Jared, Tang, Hua, Boerwinkle, Eric, Kamatani, Yoichiro, Matsuda, Koichi, Kamatani, Naoyuki, Nakamura, Yusuke, Kubo, Michiaki, Liu, Simin, Dehghan, Abba, Felix, Janine F, Hofman, Albert, Uitterlinden, André G, van Duijn, Cornelia M, Franco, Oscar H, Longo, Dan L, Singleton, Andrew B, Psaty, Bruce M, Evans, Michelle K, Cupples, L. Adrienne, Rotter, Jerome I, O'Donnell, Christopher J, Takahashi, Atsushi, Wilson, James G, Ganesh, Santhi K, Nalls, Mike A, Arepalli, S, Bandinelli, S, Biffi, A, Bis, Jc, Boerwinkle, E, Chakravarti, A, Chen, Mh, Chong, S, Coresh, J, Couper, Dj, Cupples, L, Dehghan, A, Do'Ring, A, Eiriksdottir, G, Felix, Jf, Ferrucci, L, Folsom, Ar, Fox, C, Frayling, Tm, Ganesh, Sk, Garcia, M, Garner, Sf, Gasparini, Paolo, Gieger, C, Glazer, Nl, Gouskova, Na, Greinacher, A, Gudnason, V, Harris, Tb, Hernandez, Dg, Hofman, A, Illig, T, Kamatani, Y, Kamatani, N, Kubo, M, Kuhnel, B, Lagou, V, Lettre, G, Levi, D, Lin, J, Liu, Y, Longo, Dl, Lumley, T, Mangino, M, Matsuda, K, Meisinger, C, Melzer, D, Menzel, S, Moore, M, Nakamura, Y, Nalls, Ma, Nauck, M, O'Donnell, Cj, Okada, Y, Oostra, Ba, Ouwehand, Wh, Patel, Kv, Pirastu, Nicola, Pistis, Giorgio, Prokisch, H, Prokopenko, I, Psaty, Bm, Reiner, Ap, Rendon, A, Sambrook, J, Singleton, Ab, Smith, Av, Soranzo, N, Spector, Td, Stephens, J, Stumvoll, M, Takahashi, A, Tanaka, T, Taylor, K, Teumer, A, Thein, Sl, To'Njes, A, Toniolo, D, Tsunoda, T, Uitterlinden, Ag, van Duijn, Cm, van Rooij, Fj, Vo'Lker, U, Vo'Lzke, H, Wichmann, H., Wiggins, Kl, Wilson, Jg, Witteman, Jc, Wood, Ar, Yamamoto, K, Yang, Q, Zakai, Na, Austin, Ma, Becker, Dm, Britton, A, Chen, Z, Couper, D, Curb, J, Dean, E, Eaton, Cb, Evans, Mk, Fornage, M, Grant, Sf, Hernandez, D, Kamatini, N, Keating, Bj, Lacroix, A, Lange, La, Liu, S, Lohman, K, Mathias, R, Meng, Y, Mohler ER, 3rd, Musani, S, Palmer, Cd, Papanicolaou, Gj, Snively, Bm, Tang, H, Taylor HA, Jr, Thomson, C, Yanek, Lr, Yang, L, Ziv, E, Zonderman, Ab, Higasa, K, Hirota, T, Hosono, N, Kumasaka, N, Ohmiya, H, Tamari, M, Yamaguchi Kabata, Y, and Yamamoto, K.
Subjects: Linkage disequilibrium, Genotype, Quantitative Trait Loci, White blood cell count, Single-nucleotide polymorphism, Genome-wide association study, Quantitative trait locus, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, White People, white blood cell phenotypes, Leukocyte Count, SDG 3 - Good Health and Well-being, Asian People, Polymorphism (computer science), Genetics, Leukocytes, Humans, Allele, Molecular Biology, Genetics (clinical), White blood cell count, Trans-ethnic meta-analysis, white blood cell phenotypes, Genome, Human, Association Studies Articles, Bayes Theorem, General Medicine, Heritability, Black or African American, Phenotype, Trans-ethnic meta-analysis, Genome-Wide Association Study
Abstract: White blood cell (WBC) count is a common clinical measure used as a predictor of certain aspects of human health, including immunity and infection status. WBC count is also a complex trait that varies among individuals and ancestry groups. Differences in linkage disequilibrium structure and heterogeneity in allelic effects are expected to play a role in the associations observed between populations. Prior genome-wide association study (GWAS) meta-analyses have identified genomic loci associated with WBC and its subtypes, but much of the heritability of these phenotypes remains unexplained. Using GWAS summary statistics for over 50 000 individuals from three diverse populations (Japanese, African-American and European ancestry), a Bayesian model methodology was employed to account for heterogeneity between ancestry groups. This approach was used to perform a trans-ethnic meta-analysis of total WBC, neutrophil and monocyte counts. Ten previously known associations were replicated and six new loci were identified, including several regions harboring genes related to inflammation and immune cell function. Ninety-five percent credible interval regions were calculated to narrow the association signals and fine-map the putatively causal variants within loci. Finally, a conditional analysis was performed on the most significant SNPs identified by the trans-ethnic meta-analysis (MA), and nine secondary signals within loci previously associated with WBC or its subtypes were identified. This work illustrates the potential of trans-ethnic analysis and ascribes a critical role to multi-ethnic cohorts and consortia in exploring complex phenotypes with respect to variants that lie outside the European-biased GWAS pool.
Published: 2014

23. Type 2 diabetes transcription factor 7-like 2 (TCF7L2) risk alleles reduce beta-cell function and increase birth weight

Author: Freathy, RM, Weedon, MN, McCarthy, MI, Walker, M, Hitman, GA, Ring, SM, Ben-Shlomo, Y, Smith, GD, Hattersley, AT, and Frayling, TM
Published: 2016

24. Genome-wide association scan allowing for epistasis in type 2 diabetes

Author: Bell, JT, Timpson, NJ, Rayner, NW, Zeggini, E, Frayling, TM, Hattersley, AT, Morris, AP, and McCarthy, MI
Abstract: In the presence of epistasis multilocus association tests of human complex traits can provide powerful methods to detect susceptibility variants. We undertook multilocus analyses in 1924 type 2 diabetes cases and 2938 controls from the Wellcome Trust Case Control Consortium (WTCCC). We performed a two-dimensional genome-wide association (GWA) scan using joint two-locus tests of association including main and epistatic effects in 70,236 markers tagging common variants. We found two-locus association at 79 SNP-pairs at a Bonferroni-corrected P-value = 0.05 (uncorrected P-value = 2.14 × 10⁻¹¹). The 79 pair-wise results always contained rs11196205 in TCF7L2 paired with 79 variants including confirmed variants in FTO, TSPAN8, and CDKAL1, which are associated in the absence of epistasis. However, the majority (82%) of the 79 variants did not have compelling single-locus association signals (P-value = 5 × 10⁻⁴). Analyses conditional on the single-locus effects at TCF7L2 established that the joint two-locus results could be attributed to single-locus association at TCF7L2 alone. Interaction analyses among the peak 80 regions and among 23 previously established diabetes candidate genes identified five SNP-pairs with case-control and case-only epistatic signals. Our results demonstrate the feasibility of systematic scans in GWA data, but confirm that single-locus association can underlie and obscure multilocus findings.
Published: 2016

25. Linkage studies of the Type 2 diabetes susceptibility locus on chromosome 1q: Combined analysis of 1200 UK and French affected sibpairs

Author: Groves, CJ, Wiltshire, S, Menzel, S, Bennett, A, Hattersley, AT, Frayling, TM, Walker, M, Levy, JC, O'Rahilly, S, Hitman, GA, Cardon, LR, Dina, C, and Froguel, P
Published: 2016

26. Population-specific risk of type 2 diabetes conferred by HNF4A P2 promoter variants: a lesson for replication studies

Author: Barroso, I, Luan, J, Wheeler, E, Whittaker, P, Wasson, J, Zeggini, E, Weedon, MN, Hunt, S, Venkatesh, R, Frayling, TM, Delgado, M, Neuman, RJ, Zhao, J, Sherva, R, Glaser, B, Walker, M, Hitman, G, McCarthy, MI, Hattersley, AT, Permutt, MA, Wareham, NJ, and Deloukas, P
Abstract: OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the P2 promoter region of HNF4A were originally shown to be associated with predisposition for type 2 diabetes in Finnish, Ashkenazi, and, more recently, Scandinavian populations, but they generated conflicting results in additional populations. We aimed to investigate whether data from a large-scale mapping approach would replicate this association in novel Ashkenazi samples and in U.K. populations and whether these data would allow us to refine the association signal. RESEARCH DESIGN AND METHODS: Using a dense linkage disequilibrium map of 20q, we selected SNPs from a 10-Mb interval centered on HNF4A. In a staged approach, we first typed 4,608 SNPs in case-control populations from four U.K. populations and an Ashkenazi population (n = 2,516). In phase 2, a subset of 763 SNPs was genotyped in 2,513 additional samples from the same populations. RESULTS: Combined analysis of both phases demonstrated association between HNF4A P2 SNPs (rs1884613 and rs2144908) and type 2 diabetes in the Ashkenazim (n = 991; P < 1.6 x 10(-6)). Importantly, these associations are significant in a subset of Ashkenazi samples (n = 531) not previously tested for association with P2 SNPs (odds ratio [OR] approximately 1.7; P < 0.002), thus providing replication within the Ashkenazim. In the U.K. populations, this association was not significant (n = 4,022; P > 0.5), and the estimate for the OR was much smaller (OR 1.04; [95%CI 0.91-1.19]). CONCLUSIONS: These data indicate that the risk conferred by HNF4A P2 is significantly different between U.K. and Ashkenazi populations (P < 0.00007), suggesting that the underlying causal variant remains unidentified. Interactions with other genetic or environmental factors may also contribute to this difference in risk between populations.
Published: 2016

27. Linkage analysis in the Diabetes (UK) Warren 2 sibpair repository supports localisation of a type 2 diabetes susceptibility gene to chromosome 1q21-24

Author: McCarthy, MI, Hattersley, AT, Walker, M, Hitman, GA, Levy, JC, O'Rahilly, S, Lathrop, GM, Simecek, N, Wishart, M, Dhillon, R, Fletcher, C, Frayling, TM, Bennett, A, Groves, C, Smedley, D, Menzel, S, and Wiltshire, S
Published: 2016

28. Common variation in the LMNA gene increases susceptibility to type 2 diabetes

Author: Owen, KR, Groves, CJ, Zeggini, E, Hitman, G, Walker, M, Frayling, TM, Hattersley, AT, and McCarthy, MI
Published: 2016

29. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

Author: Burton, PR, Clayton, DG, Cardon, LR, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, DP, McCarthy, MI, Ouwehand, WH, Samani, NJ, Todd, JA, Donnelly, P, Barrett, JC, Davison, D, Easton, D, Evans, DM, Leung, HT, Marchini, JL, Morris, AP, Spencer, CC, Tobin, MD, Attwood, AP, Boorman, JP, Cant, B, Everson, U, Hussey, JM, Jolley, JD, Knight, AS, Koch, K, Meech, E, Nutland, S, Prowse, CV, Stevens, HE, Taylor, NC, Walters, GR, Walker, NM, Watkins, NA, Winzer, T, Jones, RW, McArdle, WL, Ring, SM, Strachan, DP, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon-Smith, K, Jones, L, Fraser, C, Green, EK, Grozeva, D, Hamshere, ML, Holmans, PA, Jones, IR, Kirov, G, Moskivina, V, Nikolov, I, O'Donovan, MC, Owen, MJ, Collier, DA, Elkin, A, Farmer, A, Williamson, R, McGuffin, P, Young, AH, Ferrier, IN, Ball, SG, Balmforth, AJ, Barrett, JH, Bishop, TD, Iles, MM, Maqbool, A, Yuldasheva, N, Hall, AS, Braund, PS, Dixon, RJ, Mangino, M, Stevens, S, Thompson, JR, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, CW, Nimmo, ER, Satsangi, J, Fisher, SA, Forbes, A, Lewis, CM, Onnie, CM, Prescott, NJ, Sanderson, J, Matthew, CG, Barbour, J, Mohiuddin, MK, Todhunter, CE, Mansfield, JC, Ahmad, T, Cummings, FR, Jewell, DP, Webster, J, Brown, MJ, Lathrop, MG, Connell, J, Dominiczak, A, Marcano, CA, Burke, B, Dobson, R, Gungadoo, J, Lee, KL, Munroe, PB, Newhouse, SJ, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, IN, Donovan, H, Eyre, S, Gilbert, PD, Hilder, SL, Hinks, AM, John, SL, Potter, C, Silman, AJ, Symmons, DP, Thomson, W, Worthington, J, Dunger, DB, Widmer, B, Frayling, TM, Freathy, RM, Lango, H, Perry, JR, Shields, BM, Weedon, MN, Hattersley, AT, Hitman, GA, Walker, M, Elliott, KS, Groves, CJ, Lindgren, CM, Rayner, NW, Timpson, NJ, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, AV, Bradbury, LA, Farrar, C, Pointon, JJ, Wordsworth, P, Brown, MA, Franklyn, JA, Heward, JM, Simmonds, MJ, Gough, SC, Seal, S, Stratton, MR, Rahman, N, Ban, M, Goris, A, Sawcer, SJ, Compston, A, Conway, D, Jallow, M, Rockett, KA, Bumpstead, SJ, Chaney, A, Downes, K, Ghori, MJ, Gwilliam, R, Hunt, SE, Inouye, M, Keniry, A, King, E, McGinnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, NJ, Ferreira, T, Pereira-Gale, J, Hallgrimsdo'ttir, IB, Howie, BN, Su, Z, Teo, YY, Vukcevic, D, Bentley, D, Mitchell, SL, Newby, PR, Brand, OJ, Carr-Smith, J, Pearce, SH, Reveille, JD, Zhou, X, Sims, AM, Dowling, A, Taylor, J, Doan, T, Davis, JC, Savage, L, Ward, MM, Learch, TL, Weisman, MH, and Brown, M
Subjects: Linkage disequilibrium, Multiple Sclerosis, Genotype, Population, Single-nucleotide polymorphism, Genome-wide association study, Autoimmunity, Breast Neoplasms, Biology, medicine.disease_cause, Aminopeptidases, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Article, Minor Histocompatibility Antigens, Genetics, medicine, Humans, Spondylitis, Ankylosing, Receptors, Immunologic, education, Genetic association, education.field_of_study, Ankylosing spondylitis, Thyroiditis, Autoimmune, Chromosome Mapping, Receptors, Interleukin, medicine.disease, Endoplasmic reticulum aminopeptidase 2, Genetics, Population, Haplotypes, Case-Control Studies, Immunology, North America
Abstract: We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
Published: 2016

30. Assessment of the role of genetic variation in the transient neonatal diabetes (TNDM) region on chromosome 6q24 in type 2 diabetes: a comparative genomic and haplotype approach

Author: Gloyn, AL, MacKay, DJG, Weedon, MN, McCarthy, MI, Walker, M, Hitman, G, Sampson, M, Knight, BA, Hattersley, AT, and Frayling, TM
Published: 2016

31. Fine-mapping type 2 diabetes causal variants on chromosome 9p21 in 2000 UK cases and 3000 unselected controls

Author: Morris, A, Prokopenko, I, Akan, P, Lango, H, Zeggini, E, Frayling, TM, Deloukas, P, Hattersley, AT, and McCarthy, MI
Published: 2016

32. Calcium/calmodulin dependent protein kinase II genes: Genomic structure and screening for variants in subjects with Type 2 diabetes

Author: Gloyn, AL, Desai, M, Clark, A, Holman, RR, Frayling, TM, Hattersley, AT, and Ashcroft, SJH
Published: 2016

33. Common variation in the LMNA gene (encoding lamin A/C) and type 2 diabetes: association analyses in 9,518 subjects

Author: Owen, KR, Groves, CJ, Hanson, RL, Knowler, WC, Shuldiner, AR, Elbein, SC, Mitchell, BD, Froguel, P, Ng, MC, Chan, JC, Jia, W, Deloukas, P, Hitman, GA, Walker, M, Frayling, TM, Hattersley, AT, Zeggini, E, and McCarthy, MI
Abstract: Mutations in the LMNA gene (encoding lamin A/C) underlie familial partial lipodystrophy, a syndrome of monogenic insulin resistance and diabetes. LMNA maps to the well-replicated diabetes-linkage region on chromosome 1q, and there are reported associations between LMNA single nucleotide polymorphisms (SNPs) (particularly rs4641; H566H) and metabolic syndrome components. We examined the relationship between LMNA variation and type 2 diabetes (using six tag SNPs capturing >90% of common variation) in several large datasets. Analysis of 2,490 U.K. diabetic case and 2,556 control subjects revealed no significant associations at either genotype or haplotype level: the minor allele at rs4641 was no more frequent in case subjects (allelic odds ratio [OR] 1.07 [95% CI 0.98-1.17], P = 0.15). In 390 U.K. trios, family-based association analyses revealed nominally significant overtransmission of the major allele at rs12063564 (P = 0.01), which was not corroborated in other samples. Finally, genotypes for 2,817 additional subjects from the International 1q Consortium revealed no consistent case-control or family-based associations with LMNA variants. Across all our data, the OR for the rs4641 minor allele approached but did not attain significance (1.07 [0.99-1.15], P = 0.08). Our data do not therefore support a major effect of LMNA variation on diabetes risk. However, in a meta-analysis including other available data, there is evidence that rs4641 has a modest effect on diabetes susceptibility (1.10 [1.04-1.16], P = 0.001).
Published: 2016

34. Large-scale type 2 diabetes association analysis of low-frequency nonsynonymous coding variants in the HNF4A gene including up to 17,600 individuals

Author: Mohammadi, BJ, Groves, CJ, Herrera, B, Frayling, TM, Hattersley, AT, Gloyn, AL, and McCarthy, MI
Published: 2016

35. A genome scan reveals heterogeneity among European families with maturity onset diabetes of the young

Author: Frayling, TM, Menzel, S, Wishart, M, Vaxillaire, M, Lindgren, C, Tuomi, T, Wang, Y, Brown, A, Bulman, MP, Ellard, S, Evans, JC, Rao, PVS, Mills, J, Tack, C, Dina, C, Froguel, P, Groop, L, Mahtani, M, and Hattersley, AT
Published: 2016

36. Stratified analysis of the Wellcome Trust Case Control Consortium scan for type 2 diabetes reveals susceptibility loci that may affect age of diagnosis

Author: Fernandez-Cadenas, I, Prokopenko, I, Timpson, NJ, Boraska, V, Rayner, NW, Hattersley, AT, Frayling, TM, Zeggini, E, Lindgren, CM, and McCarthy, MI
Published: 2016

37. Genome-wide search for multiple loci in type 2 diabetes

Author: Bell, JT, Elliot, K, Morris, A, Groves, CJ, Fiddy, SE, Frayling, TM, Hattersley, AT, Walker, M, Hitman, GA, McCarthy, MI, and Wiltshire, S
Published: 2016

38. Genetic Basis for Gestation Length

Author: Pennell, CE, Warrington, NM, Mook-Kanamori, D, Lye, SJ, Newnham, JP, Palmer, LJ, Jaddoe, VWV, Freathy, RM, Jacobssen, B, Holloway, J, McCarthy, MI, Frayling, TM, Consortium, PGP, and Consortium, EGG
Published: 2016

39. Common genetic variants highlight the role of insulin resistance and body fat distribution in type 2 diabetes, independent of obesity

Author: Scott RA, Fall T, Pasko D, Barker A, Sharp SJ, Arriola L, Balkau B, Barricarte A, Barroso I, Boeing H, Clavel Chapelon F, Crowe FL, Dekker JM, Fagherazzi G, Ferrannini E, Forouhi NG, Franks PW, Gavrila D, Giedraitis V, Grioni S, Groop LC, Kaaks R, Key TJ, Kühn T, Lotta LA, Nilsson PM, Overvad K, Palli D, Quirós JR, Rolandsson O, Roswall N, Sacerdote C, Sala N, Sánchez MJ, Schulze MB, Siddiq A, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, van der A. DL, Yaghootkar H, RISC Study Group, EPIC InterAct Consortium, McCarthy MI, Semple RK, Riboli E, Walker M, Ingelsson E, Frayling TM, Savage DB, Langenberg C, Wareham N.J., PANICO, SALVATORE, Sharp, Stephen [0000-0003-2375-1440], Barroso, Ines [0000-0001-5800-4520], Forouhi, Nita [0000-0002-5041-248X], Semple, Robert [0000-0001-6539-3069], Savage, David [0000-0002-7857-7032], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Scott, Ra, Fall, T, Pasko, D, Barker, A, Sharp, Sj, Arriola, L, Balkau, B, Barricarte, A, Barroso, I, Boeing, H, Clavel Chapelon, F, Crowe, Fl, Dekker, Jm, Fagherazzi, G, Ferrannini, E, Forouhi, Ng, Franks, Pw, Gavrila, D, Giedraitis, V, Grioni, S, Groop, Lc, Kaaks, R, Key, Tj, Kühn, T, Lotta, La, Nilsson, Pm, Overvad, K, Palli, D, Panico, Salvatore, Quirós, Jr, Rolandsson, O, Roswall, N, Sacerdote, C, Sala, N, Sánchez, Mj, Schulze, Mb, Siddiq, A, Slimani, N, Sluijs, I, Spijkerman, Am, Tjonneland, A, Tumino, R, van der A., Dl, Yaghootkar, H, RISC Study, Group, EPIC InterAct, Consortium, Mccarthy, Mi, Semple, Rk, Riboli, E, Walker, M, Ingelsson, E, Frayling, Tm, Savage, Db, Langenberg, C, and Wareham, N. J.
Subjects: Adult, Male, Genetic Variation, Alanine Transaminase, gamma-Glutamyltransferase, Glucose Tolerance Test, Middle Aged, Overweight, Polymorphism, Single Nucleotide, Body Mass Index, Cohort Studies, Diabetes Mellitus, Type 2, Insulin Secretion, Body Composition, Glucose Clamp Technique, Body Fat Distribution, Humans, Insulin, Female, Genetic Predisposition to Disease, Obesity, Insulin Resistance, Waist Circumference, Aged
Abstract: We aimed to validate genetic variants as instruments for insulin resistance and secretion, to characterize their association with intermediate phenotypes, and to investigate their role in type 2 diabetes (T2D) risk among normal-weight, overweight, and obese individuals. We investigated the association of genetic scores with euglycemic-hyperinsulinemic clamp- and oral glucose tolerance test-based measures of insulin resistance and secretion and a range of metabolic measures in up to 18,565 individuals. We also studied their association with T2D risk among normal-weight, overweight, and obese individuals in up to 8,124 incident T2D cases. The insulin resistance score was associated with lower insulin sensitivity measured by M/I value (β in SDs per allele [95% CI], -0.03 [-0.04, -0.01]; P = 0.004). This score was associated with lower BMI (-0.01 [-0.01, -0.0]; P = 0.02) and gluteofemoral fat mass (-0.03 [-0.05, -0.02; P = 1.4 × 10(-6)) and with higher alanine transaminase (0.02 [0.01, 0.03]; P = 0.002) and γ-glutamyl transferase (0.02 [0.01, 0.03]; P = 0.001). While the secretion score had a stronger association with T2D in leaner individuals (Pinteraction = 0.001), we saw no difference in the association of the insulin resistance score with T2D among BMI or waist strata (Pinteraction > 0.31). While insulin resistance is often considered secondary to obesity, the association of the insulin resistance score with lower BMI and adiposity and with incident T2D even among individuals of normal weight highlights the role of insulin resistance and ectopic fat distribution in T2D, independently of body size.
Published: 2014

40. A novel common variant in DCST2 is associated with length in early life and height in adulthood

Author: van der Valk RJ, Kreiner-Møller E, Kooijman MN, Guxens M, Stergiakouli E, Sääf A, Bradfield JP, Geller F, Hayes MG, Cousminer DL, Körner A, Thiering E, Curtin JA, Myhre R, Huikari V, Joro R, Kerkhof M, Warrington NM, Pitkänen N, Ntalla I, Horikoshi M, Veijola R, Freathy RM, Teo YY, Barton SJ, Evans DM, Kemp JP, St Pourcain B, Ring SM, Davey Smith G, Bergström A, Kull I, Hakonarson H, Mentch FD, Bisgaard H, Chawes B, Stokholm J, Waage J, Eriksen P, Sevelsted A, Melbye M, Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium, van Duijn CM, Medina-Gomez C, Hofman A, de Jongste JC, Taal HR, Uitterlinden AG, Genetic Investigation of ANthropometric Traits (GIANT) Consortium, Armstrong LL, Eriksson J, Palotie A, Bustamante M, Estivill X, Gonzalez JR, Llop S, Kiess W, Mahajan A, Flexeder C, Tiesler CM, Murray CS, Simpson A, Magnus P, Sengpiel V, Hartikainen AL, Keinanen-Kiukaanniemi S, Lewin A, Da Silva Couto Alves A, Blakemore AI, Buxton JL, Kaakinen M, Rodriguez A, Sebert S, Vaarasmaki M, Lakka T, Lindi V, Gehring U, Postma DS, Ang W, Newnham JP, Lyytikäinen LP, Pahkala K, Raitakari OT, Panoutsopoulou K, Zeggini E, Boomsma DI, Groen-Blokhuis M, Ilonen J, Franke L, Hirschhorn JN, Pers TH, Liang L, Huang J, Hocher B, Knip M, Saw SM, Holloway JW, Melén E, Grant SF, Feenstra B, Lowe WL, Widén E, Sergeyev E, Grallert H, Custovic A, Jacobsson B, Jarvelin MR, Atalay M, Koppelman GH, Pennell CE, Niinikoski H, Dedoussis GV, Mccarthy MI, Frayling TM, Sunyer J, Timpson NJ, Rivadeneira F, Bønnelykke K, Jaddoe VW, and Early Growth Genetics (EGG) Consortium
Subjects: Genetic variants, DCST2, Single nucleotide polymorphisms (SNPs), Skeletal growth, Adult height, Early growth
Abstract: Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height. R.M.F. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Wellcome Trust grant 085541/Z/08/Z). T.H.P. is supported by The Danish Council for Independent Research Medical Sciences (FSS) The Alfred Benzon Foundation. B.F. is supported by an Oak Foundation fellowship. M.M. is a Wellcome Trust Senior Investigator (Wellcome Trust grant 090532) and a NIHR Senior Investigator. T.M.F. is supported by the European Research Council grant: SZ-245 50371- GLUCOSEGENES-FP7-IDEAS-ERC. F.R. (VIDI 016.136.367) and V.W.V.J. (VIDI 016.136.361) received grants from the Netherlands Organization for Health Research and Development.
Published: 2015

41. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Author: ICBP Consortium, AGEN Consortium, CHARGe-Heart Failure Group, ECHOGen Consortium, CARDIOGRAM, Abecasis, GR., Adair, LS., Alexander, M., Altshuler, D., Amin, N., Arking, DE., Arora, P., Aulchenko, Y., Bakker, SJ., Bandinelli, S., Barroso, I., Beckmann, JS., Beilby, JP., Bergman, RN., Bergmann, S., Bis, JC., Boehnke, M., Bonnycastle, LL., Bornstein, SR., Bots, ML., Bragg-Gresham, JL., Brand, SM., Brand, E., Braund, PS., Brown, MJ., Burton, PR., Casas, JP., Caulfield, MJ., Chakravarti, A., Chambers, JC., Chandak, GR., Chang, YP., Charchar, FJ., Chaturvedi, N., Shin Cho, Y., Clarke, R., Collins, FS., Collins, R., Connell, JM., Cooper, JA., Cooper, MN., Cooper, RS., Corsi, AM., Dörr, M., Dahgam, S., Danesh, J., Davey Smith, G., Day, IN., Deloukas, P., Denniff, M., Dominiczak, AF., Dong, Y., Doumatey, A., Elliott, P., Elosua, R., Erdmann, J., Eyheramendy, S., Farrall, M., Fava, C., Forrester, T., Fowkes, FG., Fox, ER., Frayling, TM., Galan, P., Ganesh, SK., Garcia, M., Gaunt, TR., Glazer, NL., Go, MJ., Goel, A., Grässler, J., Grobbee, DE., Groop, L., Guarrera, S., Guo, X., Hadley, D., Hamsten, A., Han, BG., Hardy, R., Hartikainen, AL., Heath, S., Heckbert, SR., Hedblad, B., Hercberg, S., Hernandez, D., Hicks, AA., Hilton, G., Hingorani, AD., Bolton, JA., Hopewell, JC., Howard, P., Humphries, SE., Hunt, SC., Hveem, K., Ikram, MA., Islam, M., Iwai, N., Jarvelin, MR., Jackson, AU., Jafar, TH., Janipalli, CS., Johnson, T., Kathiresan, S., Khaw, KT., Kim, HL., Kinra, S., Kita, Y., Kivimaki, M., Kooner, JS., Kumar, MJ., Kuh, D., Kulkarni, SR., Kumari, M., Kuusisto, J., Kuznetsova, T., Laakso, M., Laan, M., Laitinen, J., Lakatta, EG., Langefeld, CD., Larson, MG., Lathrop, M., Lawlor, DA., Lawrence, RW., Lee, JY., Lee, NR., Levy, D., Li, Y., Longstreth, WT., Luan£££Jian'an£££ J., Lucas, G., Ludwig, B., Mangino, M., Mani, KR., Marmot, MG., Mattace-Raso, FU., Matullo, G., McArdle, WL., McKenzie, CA., Meitinger, T., Melander, O., Meneton, P., Meschia, JF., Miki, T., Milaneschi, Y., Mohlke, KL., Mooser, V., Morken, MA., Morris, RW., Mosley, TH., Najjar, S., Narisu, N., Newton-Cheh, C., Nguyen, KD., Nilsson, P., Nyberg, F., O'Donnell, CJ., Ogihara, T., Ohkubo, T., Okamura, T., Ong, RT., Ongen, H., Onland-Moret, NC., O'Reilly, PF., Org, E., Orru, M., Palmas, W., Palmen, J., Palmer, LJ., Palmer, ND., Parker, AN., Peden, JF., Peltonen, L., Perola, M., Pihur, V., Platou, CG., Plump, A., Prabhakaran, D., Psaty, BM., Raffel, LJ., Rao, DC., Rasheed, A., Ricceri, F., Rice, KM., Rosengren, A., Rotter, JI., Rudock, ME., Sõber, S., Salako, T., Saleheen, D., Salomaa, V., Samani, NJ., Schwartz, SM., Schwarz, PE., Scott, LJ., Scott, J., Scuteri, A., Sehmi, JS., Seielstad, M., Seshadri, S., Sharma, P., Shaw-Hawkins, S., Shi, G., Shrine, NR., Sijbrands, EJ., Sim, X., Singleton, A., Sjögren, M., Smith, NL., Soler Artigas, M., Spector, TD., Staessen, JA., Stancakova, A., Steinle, NI., Strachan, DP., Stringham, HM., Sun, YV., Swift, AJ., Tabara, Y., Tai, ES., Talmud, PJ., Taylor, A., Terzic, J., Thelle, DS., Tobin, MD., Tomaszewski, M., Tripathy, V., Tuomilehto, J., Tzoulaki, I., Uda, M., Ueshima, H., Uiterwaal, CS., Umemura, S., van der Harst, P., van der Schouw YT., van Gilst WH., Vartiainen, E., Vasan, RS., Veldre, G., Verwoert, GC., Viigimaa, M., Vinay, DG., Vineis, P., Voight, BF., Vollenweider, P., Wagenknecht, LE., Wain, LV., Wang, X., Wang, TJ., Wareham, NJ., Watkins, H., Weder, AB., Whincup, PH., Wiggins, KL., Witteman, JC., Wong, A., Wu, Y., Yajnik, CS., Yao, J., Young, JH., Zelenika, D., Zhai, G., Zhang, W., Zhang, F., Zhao, JH., Zhu, H., Zhu, X., Zitting, P., Zukowska-Szczechowska, E., Okada, Y., Wu, JY., Gu, D., Takeuchi, F., Takahashi, A., Maeda, S., Tsunoda, T., Chen, P., Lim, SC., Wong, TY., Liu, J., Young, TL., Aung, T., Teo, YY., Kim, YJ., Kang, D., Chen, CH., Tsai, FJ., Chang, LC., Fann, SJ., Mei, H., Hixson, JE., Chen, S., Katsuya, T., Isono, M., Albrecht, E., Yamamoto, K., Kubo, M., Nakamura, Y., Kamatani, N., Kato, N., He, J., Chen, YT., Tanaka, T., Reilly, MP., Schunkert, H., Assimes, TL., Hall, A., Hengstenberg, C., König, IR., Laaksonen, R., McPherson, R., Thompson, JR., Thorsteinsdottir, U., Ziegler, A., Absher, D., Chen, L., Cupples, LA., Halperin, E., Li, M., Musunuru, K., Preuss, M., Schillert, A., Thorleifsson, G., Wells, GA., Holm, H., Roberts, R., Stewart, AF., Fortmann, S., Go, A., Hlatky, M., Iribarren, C., Knowles, J., Myers, R., Quertermous, T., Sidney, S., Risch, N., Tang, H., Blankenberg, S., Schnabel, R., Sinning, C., Lackner, KJ., Tiret, L., Nicaud, V., Cambien, F., Bickel, C., Rupprecht, HJ., Perret, C., Proust, C., Münzel, TF., Barbalic, M., Chen, IY., Demissie-Banjaw, S., Folsom, A., Lumley, T., Marciante, K., Taylor, KD., Volcik, K., Gretarsdottir, S., Gulcher, JR., Kong, A., Stefansson, K., Thorgeirsson, G., Andersen, K., Fischer, M., Grosshennig, A., Linsel-Nitschke, P., Stark, K., Schreiber, S., Aherrahrou, Z., Bruse, P., Doering, A., Klopp, N., Diemert, P., Loley, C., Medack, A., Nahrstedt, J., Peters, A., Wagner, AK., Willenborg, C., Böhm, BO., Dobnig, H., Grammer, TB., Hoffmann, MM., Meinitzer, A., Winkelmann, BR., Pilz, S., Renner, W., Scharnagl, H., Stojakovic, T., Tomaschitz, A., Winkler, K., Guiducci, C., Burtt, N., Gabriel, SB., Dandona, S., Jarinova, O., Qu, L., Wilensky, R., Matthai, W., Hakonarson, HH., Devaney, J., Burnett, MS., Pichard, AD., Kent, KM., Satler, L., Lindsay, JM., Waksman, R., Knouff, CW., Waterworth, DM., Walker, MC., Epstein, SE., Rader, DJ., Nelson, CP., Wright, BJ., Balmforth, AJ., Ball, SG., Loehr, LR., Rosamond, WD., Benjamin, E., Haritunians, T., Couper, D., Murabito, J., Wang, YA., Stricker, BH., Chang, PP., Willerson, JT., Felix, SB., Watzinger, N., Aragam, J., Zweiker, R., Lind, L., Rodeheffer, RJ., Greiser, KH., Deckers, JW., Stritzke, J., Ingelsson, E., Kullo, I., Haerting, J., Reffelmann, T., Redfield, MM., Werdan, K., Mitchell, GF., Arnett, DK., Gottdiener, JS., Blettner, M., Friedrich, N., Pattaro, C., 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Abstract: Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
Published: 2016

42. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

Author: Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, Loos, RJF, Kilpelainen, TO, Carli, J F M, Skowronski, A A, Sun, Q, Kriebel, J, Feitosa, MF, Hedman, AK, Drong, AW, Hayes, J E, Zhao, JH, Pers, TH, Schick, U, Grarup, N, Kutalik, Z, Trompet, S, Mangino, M, Kristiansson, K, Beekman, M, Lyytikainen, LP, Eriksson, J, Henneman, Peter, Lahti, J, Tanaka, T, Luan, JA, Del Greco, F, Pasko, D, Renstrom, F, Willems, SM, Mahajan, A, Rose, LM, Guo, XQ, Liu, YM, Kleber, ME, Perusse, L, Gaunt, T, Ahluwalia, TS, Sung, YJ, Ramos, YF, Amin, Najaf, Amuzu, A, Barroso, I, Bellis, C, Blangero, J, Buckley, BM, Bohringer, S, Chen, YDI, de Craen, A J N, Crosslin, DR, Dale, CE, Dastani, Z, Day, FR, Deelen, J, Delgado, GE, Demirkan, Ayse, Finucane, FM, Ford, I, Garcia, ME, Gieger, C, Gustafsson, S, Hallmans, G, Hankinson, SE, Havulinna, AS, Herder, Cindy, Hernandez, D, Hicks, AA, Hunter, DJ, Illig, T, Ingelsson, E, Ioan-Facsinay, A, Jansson, JO, Jenny, NS, Jorgensen, ME, Jorgensen, T, Karlsson, M, Koenig, W, Kraft, P, Kwekkeboom, J, Laatikainen, T, Ladwig, KH, LeDuc, C A, Lowe, G, Lu, YC, Marques-Vidal, P, Meisinger, C, Menni, C, Morris, AP, Myers, RH, Mannisto, S, Nalls, MA, Paternoster, L, Peters, A, Pradhan, A D, Rankinen, T, Rasmussen-Torvik, LJ, Rathmann, W, Rice, TK, Richards, JB, Ridker, PM, Sattar, N, Savage, DB, Soderberg, S, Timpson, NJ, Vandenput, L, van Heemst, D, Uh, HW, Vohl, MC, Walker, M, Wichmann, HE, Widen, E, Wood, AR, Yao, J, Zeller, T, Zhang, YY, Meulenbelt, I, Kloppenburg, M, Astrup, A, Sorensen, TIA, Sarzynski, MA, Rao, DC, Jousilahti, P, Vartiainen, E, Hofman, Bert, Rivadeneira, Fernando, Uitterlinden, André, Kajantie, E, Osmond, C, Palotie, A, Eriksson, JG, Heliovaara, M, Knekt, PB, Koskinen, S, Jula, A, Perola, M, Huupponen, R K, Viikari, JS, Kahonen, M, Lehtimaki, T, Raitakari, OT, Mellstrom, D, Lorentzon, M, Casas, JP, Bandinelli, S, Marz, W, Isaacs, Aaron, van Dijk, KW, Duijn, Cornelia, Harris, TB, Bouchard, C, Allison, MA, Chasman, DI, Ohlsson, C, Lind, L, Scott, RA, Langenberg, C, Wareham, NJ, Ferrucci, L, Frayling, TM, Pramstaller, PP, Borecki, IB, Waterworth, DM, Bergmann, S, Waeber, G, Vollenweider, P, Vestergaard, H, Hansen, T, Pedersen, O, Hu, FB, Slagboom, PE (Eline), Grallert, H, Spector, TD, Jukema, JW, Klein, RJ, Schadt, EE, Franks, PW, Lindgren, CM, Leibel, R L, and Loos, RJF
Published: 2016

43. Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci

Author: Jones, SE, Tyrrell, J, Wood, AR, Beaumont, RN, Ruth, KS, Tuke, MA, Yaghootkar, H, Hu, Y, Teder-Laving, M, Hayward, C, Roenneberg, T, Wilson, JF, Del Greco, F, Hicks, AA, Shin, C, Yun, CH, Lee, SK, Metspalu, A, Byrne, EM, Gehrman, PR, Tiemeier, Henning, Allebrandt, KV, Freathy, RM, Murray, A, Hinds, DA, Frayling, TM, Weedon, MN, Jones, SE, Tyrrell, J, Wood, AR, Beaumont, RN, Ruth, KS, Tuke, MA, Yaghootkar, H, Hu, Y, Teder-Laving, M, Hayward, C, Roenneberg, T, Wilson, JF, Del Greco, F, Hicks, AA, Shin, C, Yun, CH, Lee, SK, Metspalu, A, Byrne, EM, Gehrman, PR, Tiemeier, Henning, Allebrandt, KV, Freathy, RM, Murray, A, Hinds, DA, Frayling, TM, and Weedon, MN
Abstract: Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10(-8)), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10(-12)) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10(-10)). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10(-8) on meta-analysis and eleven of these reached P< 0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10(-8)). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10(-16)) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10(-9); and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10(-9)). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10(-5)) and over-sleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the bi
Published: 2016

44. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies

Author: Reilly MP, Li M, He J, Ferguson JF, Stylianou IM, Mehta NN, Burnett MS, Devaney JM, Knouff CW, Thompson JR, Horne BD, Stewart AF, Assimes TL, Wild PS, Allayee H, Nitschke PL, Patel RS, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Martinelli N, Girelli D, Quyyumi AA, Anderson JL, Erdmann J, Hall AS, Schunkert H, Quertermous T, Blankenberg S, Hazen SL, Roberts R, Kathiresan S, Samani NJ, Epstein SE, Rader DJ, Qasim AN, DerOhannessian SL, Qu L, Cappola TP, Chen Z, Matthai W, Hakonarson HH, Wilensky R, Kent KM, Lindsay JM, Pichard AD, Satler L, Waksman R, Knoupf CW, Walker MC, Waterworth DM, Mosser V, Braund PS, Wright B, Balmforth AJ, Ball SG, Chen L, Wells GA, McPherson R, Lackner K, Munzel TF, Schillert A, Schnabel R, Zeller T, Ziegler A, Absher D, Hlatky MA, Iribaren C, Knowles JW, Linsel Nitschke P, König IR, Hengstenberg C, Nahrstaedt J, Peters A, Schreiber S, Wichmann E, Willenborg C, Su S, Bouzyk M, Vaccarino V, Zafari AM, Carlquist JF, Muhlestein JB, Olivieri O, Barnard J, Hartiala J, Tang WH, Burton PR, Clayton DG, Cardon LR, Craddock N, Deloukas P, Duncanson A, Kwiatkowski DP, McCarthy MI, Ouwehand WH, Todd JA, Donnelly P, Barrett JC, Davison D, Easton D, Evans DM, Leung HT, Marchini JL, Morris AP, Spencer CC, Tobin MD, Attwood AP, Boorman JP, Cant B, Everson U, Hussey JM, Jolley JD, Knight AS, Koch K, Meech E, Nutland S, Prowse CV, Stevens HE, Taylor NC, Walters GR, Walker NM, Watkins NA, Winzer T, Jones RW, McArdle WL, Ring SM, Strachan DP, Pembrey M, Breen G, St Clair D, Caesar S, Gordon Smith K, Jones L, Fraser C, Green EK, Grozeva D, Hamshere ML, Holmans PA, Jones IR, Kirov G, Moskvina V, Nikolov I, O'Donovan MC, Owen MJ, Collier DA, Elkin A, Farmer A, Williamson R, McGuffin P, Young AH, Ferrier IN, Barrett JH, Bishop DT, Iles MM, Maqbool A, Yuldasheva N, Dixon RJ, Mangino M, Stevens S, Bredin F, Tremelling M, Parkes M, Drummond H, Lees CW, Nimmo ER, Satsangi J, Fisher SA, Forbes A, Lewis CM, Onnie CM, Prescott NJ, Sanderson J, Mathew CG, Barbour J, Mohiuddin MK, Todhunter CE, Mansfield JC, Ahmad T, Cummings FR, Jewell DP, Webster J, Brown MJ, Lathrop M, Connell J, Dominiczak A, Marcano CA, Burke B, Dobson R, Gungadoo J, Lee KL, Munroe PB, Newhouse SJ, Onipinla A, Wallace C, Xue M, Caulfield M, Farrall M, Barton A, Bruce IN, Donovan H, Eyre S, Gilbert PD, Hider SL, Hinks AM, John SL, Potter C, Silman AJ, Symmons DP, Thomson W, Worthington J, Dunger DB, Widmer B, Frayling TM, Freathy RM, Lango H, Perry JR, Shields BM, Weedon MN, Hattersley AT, Hitman GA, Walker M, Elliott KS, Groves CJ, Lindgren CM, Rayner NW, Timpson NJ, Zeggini E, Newport M, Sirugo G, Lyons E, Vannberg F, Hill AV, Bradbury LA, Farrar C, Pointon JJ, Wordsworth P, Brown MA, Franklyn JA, Heward JM, Simmonds MJ, Gough SC, Seal S, Stratton MR, Rahman N, Ban M, Goris A, Sawcer SJ, Compston A, Conway D, Jallow M, Rockett KA, Bumpstead SJ, Chaney A, Downes K, Ghori MJ, Gwilliam R, Hunt SE, Inouye M, Keniry A, King E, McGinnis R, Potter S, Ravindrarajah R, Whittaker P, Widden C, Withers D, Cardin NJ, Ferreira T, Pereira Gale J, Hallgrimsdóttir IB, Bowie BN, Su Z, Teo YY, Vukcevic D, Bentley D, Meigs JB, Williams G, Nathan DM, MacRae CA, O'Donnell CJ, Ardissino D, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Mannucci PM, Schwartz SM, Siscovick DS, Yee J, Friedlander Y, Elosua R, Marrugat J, Lucas G, Subirana I, Sala J, Ramos R, Salomaa V, Havulinna AS, Peltonen L, Melander O, Berglund G, Voight BF, Hirschhorn JN, Asselta R, Duga S, Spreafico M, Musunuru K, Daly MJ, Purcell S, Surti A, Guiducci C, Gianniny L, Mirel D, Parkin M, Burtt N, Gabriel SB, CASARI , GIORGIO NEVIO, Reilly, Mp, Li, M, He, J, Ferguson, Jf, Stylianou, Im, Mehta, Nn, Burnett, M, Devaney, Jm, Knouff, Cw, Thompson, Jr, Horne, Bd, Stewart, Af, Assimes, Tl, Wild, P, Allayee, H, Nitschke, Pl, Patel, R, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Martinelli, N, Girelli, D, Quyyumi, Aa, Anderson, Jl, Erdmann, J, Hall, A, Schunkert, H, Quertermous, T, Blankenberg, S, Hazen, Sl, Roberts, R, Kathiresan, S, Samani, Nj, Epstein, Se, Rader, Dj, Qasim, An, Derohannessian, Sl, Qu, L, Cappola, Tp, Chen, Z, Matthai, W, Hakonarson, Hh, Wilensky, R, Kent, Km, Lindsay, Jm, Pichard, Ad, Satler, L, Waksman, R, Knoupf, Cw, Walker, Mc, Waterworth, Dm, Mosser, V, Braund, P, Wright, B, Balmforth, Aj, Ball, Sg, Chen, L, Wells, Ga, Mcpherson, R, Lackner, K, Munzel, Tf, Schillert, A, Schnabel, R, Zeller, T, Ziegler, A, Absher, D, Hlatky, Ma, Iribaren, C, Knowles, Jw, Linsel Nitschke, P, König, Ir, Hengstenberg, C, Nahrstaedt, J, Peters, A, Schreiber, S, Wichmann, E, Willenborg, C, Su, S, Bouzyk, M, Vaccarino, V, Zafari, Am, Carlquist, Jf, Muhlestein, Jb, Olivieri, O, Barnard, J, Hartiala, J, Tang, Wh, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Deloukas, P, Duncanson, A, Kwiatkowski, Dp, Mccarthy, Mi, Ouwehand, Wh, Todd, Ja, Donnelly, P, Barrett, Jc, Davison, D, Easton, D, Evans, Dm, Leung, Ht, Marchini, Jl, Morris, Ap, Spencer, Cc, Tobin, Md, Attwood, Ap, Boorman, Jp, Cant, B, Everson, U, Hussey, Jm, Jolley, Jd, Knight, A, Koch, K, Meech, E, Nutland, S, Prowse, Cv, Stevens, He, Taylor, Nc, Walters, Gr, Walker, Nm, Watkins, Na, Winzer, T, Jones, Rw, Mcardle, Wl, Ring, Sm, Strachan, Dp, Pembrey, M, Breen, G, St Clair, D, Caesar, S, Gordon Smith, K, Jones, L, Fraser, C, Green, Ek, Grozeva, D, Hamshere, Ml, Holmans, Pa, Jones, Ir, Kirov, G, Moskvina, V, Nikolov, I, O'Donovan, Mc, Owen, Mj, Collier, Da, Elkin, A, Farmer, A, Williamson, R, Mcguffin, P, Young, Ah, Ferrier, In, Barrett, Jh, Bishop, Dt, Iles, Mm, Maqbool, A, Yuldasheva, N, Dixon, Rj, Mangino, M, Stevens, S, Bredin, F, Tremelling, M, Parkes, M, Drummond, H, Lees, Cw, Nimmo, Er, Satsangi, J, Fisher, Sa, Forbes, A, Lewis, Cm, Onnie, Cm, Prescott, Nj, Sanderson, J, Mathew, Cg, Barbour, J, Mohiuddin, Mk, Todhunter, Ce, Mansfield, Jc, Ahmad, T, Cummings, Fr, Jewell, Dp, Webster, J, Brown, Mj, Lathrop, M, Connell, J, Dominiczak, A, Marcano, Ca, Burke, B, Dobson, R, Gungadoo, J, Lee, Kl, Munroe, Pb, Newhouse, Sj, Onipinla, A, Wallace, C, Xue, M, Caulfield, M, Farrall, M, Barton, A, Bruce, In, Donovan, H, Eyre, S, Gilbert, Pd, Hider, Sl, Hinks, Am, John, Sl, Potter, C, Silman, Aj, Symmons, Dp, Thomson, W, Worthington, J, Dunger, Db, Widmer, B, Frayling, Tm, Freathy, Rm, Lango, H, Perry, Jr, Shields, Bm, Weedon, Mn, Hattersley, At, Hitman, Ga, Walker, M, Elliott, K, Groves, Cj, Lindgren, Cm, Rayner, Nw, Timpson, Nj, Zeggini, E, Newport, M, Sirugo, G, Lyons, E, Vannberg, F, Hill, Av, Bradbury, La, Farrar, C, Pointon, Jj, Wordsworth, P, Brown, Ma, Franklyn, Ja, Heward, Jm, Simmonds, Mj, Gough, Sc, Seal, S, Stratton, Mr, Rahman, N, Ban, M, Goris, A, Sawcer, Sj, Compston, A, Conway, D, Jallow, M, Rockett, Ka, Bumpstead, Sj, Chaney, A, Downes, K, Ghori, Mj, Gwilliam, R, Hunt, Se, Inouye, M, Keniry, A, King, E, Mcginnis, R, Potter, S, Ravindrarajah, R, Whittaker, P, Widden, C, Withers, D, Cardin, Nj, Ferreira, T, Pereira Gale, J, Hallgrimsdóttir, Ib, Bowie, Bn, Su, Z, Teo, Yy, Vukcevic, D, Bentley, D, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, O'Donnell, Cj, Ardissino, D, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, GIORGIO NEVIO, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Mannucci, Pm, Schwartz, Sm, Siscovick, D, Yee, J, Friedlander, Y, Elosua, R, Marrugat, J, Lucas, G, Subirana, I, Sala, J, Ramos, R, Salomaa, V, Havulinna, A, Peltonen, L, Melander, O, Berglund, G, Voight, Bf, Hirschhorn, Jn, Asselta, R, Duga, S, Spreafico, M, Musunuru, K, Daly, Mj, Purcell, S, Surti, A, Guiducci, C, Gianniny, L, Mirel, D, Parkin, M, Burtt, N, and Gabriel, Sb
Subjects: Adult, Male, medicine.medical_specialty, Linkage disequilibrium, ABO, ADAMTS7 Protein, ADAMTS7, Genome-wide association study, Coronary Angiography, Polymorphism, Single Nucleotide, Linkage Disequilibrium, ABO Blood-Group System, Coronary artery disease, Gene Frequency, ABO blood group system, Internal medicine, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Myocardial infarction, Genetic risk factor, genetic locus, Coronary atherosclerosis, Aged, business.industry, coronary atherosclerosis, General Medicine, Middle Aged, medicine.disease, ADAM Proteins, myocardial infarction, Genetic Loci, Cardiology, Myocardial infarction complications, Female, business, coronary artery disease, Genome-Wide Association Study
Abstract: BACKGROUND: We tested whether genetic factors distinctly contribute to either development of coronary atherosclerosis or, specifically, to myocardial infarction in existing coronary atherosclerosis. METHODS: We did two genome-wide association studies (GWAS) with coronary angiographic phenotyping in participants of European ancestry. To identify loci that predispose to angiographic coronary artery disease (CAD), we compared individuals who had this disorder (n=12,393) with those who did not (controls, n=7383). To identify loci that predispose to myocardial infarction, we compared patients who had angiographic CAD and myocardial infarction (n=5783) with those who had angiographic CAD but no myocardial infarction (n=3644). FINDINGS: In the comparison of patients with angiographic CAD versus controls, we identified a novel locus, ADAMTS7 (p=4·98×10(-13)). In the comparison of patients with angiographic CAD who had myocardial infarction versus those with angiographic CAD but no myocardial infarction, we identified a novel association at the ABO locus (p=7·62×10(-9)). The ABO association was attributable to the glycotransferase-deficient enzyme that encodes the ABO blood group O phenotype previously proposed to protect against myocardial infarction. INTERPRETATION: Our findings indicate that specific genetic predispositions promote the development of coronary atherosclerosis whereas others lead to myocardial infarction in the presence of coronary atherosclerosis. The relation to specific CAD phenotypes might modify how novel loci are applied in personalised risk assessment and used in the development of novel therapies for CAD. FUNDING: The PennCath and MedStar studies were supported by the Cardiovascular Institute of the University of Pennsylvania, by the MedStar Health Research Institute at Washington Hospital Center and by a research grant from GlaxoSmithKline. The funding and support for the other cohorts contributing to the paper are described in the webappendix.
Published: 2011

45. The Lin28/let-7 axis regulates glucose metabolism

Author: Zhu H, Shyh Chang N, Segrè AV, Shinoda G, Shah SP, Einhorn WS, Takeuchi A, Engreitz JM, Hagan JP, Kharas MG, Urbach A, Thornton JE, Triboulet R, Gregory RI, DIAGRAM Consortium, MAGIC Investigators, Altshuler D, Daley G.Q. Voight BF, Scott LJ, Steinthorsdottir V, Morris AP, Dina C, Welch RP, Zeggini E, Huth C, Aulchenko YS, Thorleifsson G, McCulloch LJ, Ferreira T, Grallert H, Amin N, Wu G, Willer CJ, Raychaudhuri S, McCarroll SA, Langenberg C, Hofmann OM, Dupuis J, Qi L, van Hoek M, Navarro P, Ardlie K, Balkau B, Benediktsson R, Bennett AJ, Blagieva R, Boerwinkle E, Bonnycastle LL, Boström KB, Bravenboer B, Bumpstead S, Burtt NP, Charpentier G, Chines PS, Cornelis M, Couper DJ, Crawford G, Doney AS, Elliott KS, Elliott AL, Erdos MR, Fox CS, Franklin CS, Ganser M, Gieger C, Grarup N, Green T, Griffin S, Groves CJ, Guiducci C, Hadjadj S, Hassanali N, Herder C, Isomaa B, Jackson AU, Johnson PR, Jørgensen T, Kao WH, Klopp N, Kong A, Kraft P, Kuusisto J, Lauritzen T, Li M, Lieverse A, Lindgren CM, Lyssenko V, Marre M, Meitinger T, Midthjell K, Morken MA, Narisu N, Nilsson P, Owen KR, Payne F, Perry JR, Petersen AK, Platou C, Proença C, Prokopenko I, Rathmann W, Rayner NW, Robertson NR, Rocheleau G, Roden M, Sampson MJ, Saxena R, Shields BM, Shrader P, Sigurdsson G, Sparsø T, Strassburger K, Stringham HM, Sun Q, Swift AJ, Thorand B, Tichet J, Tuomi T, van Dam RM, van Haeften TW, van Herpt T, van Vliet Ostaptchouk JV, Walters GB, Weedon MN, Wijmenga C, Witteman J, Bergman RN, Cauchi S, Collins FS, Gloyn AL, Gyllensten U, Hansen T, Hide WA, Hitman GA, Hofman A, Hunter DJ, Hveem K, Laakso M, Mohlke KL, Morris AD, Palmer CN, Pramstaller PP, Rudan I, Sijbrands E, Stein LD, Tuomilehto J, Uitterlinden A, Walker M, Wareham NJ, Watanabe RM, Abecasis GR, Boehm BO, Campbell H, Daly MJ, Hattersley AT, Hu FB, Meigs JB, Pankow JS, Pedersen O, Wichmann HE, Barroso I, Florez JC, Frayling TM, Groop L, Sladek R, Thorsteinsdottir U, Wilson JF, Illig T, Froguel P, van Duijn CM, Stefansson K, Boehnke M, McCarthy MI, Soranzo N, Wheeler E, Glazer NL, Bouatia Naji N, Mägi R, Randall J, Johnson T, Elliott P, Rybin D, Henneman P, Dehghan A, Hottenga JJ, Song K, Goel A, Egan JM, Lajunen T, Doney A, Voight BF, Kanoni S, Cavalcanti Proença C, Kumari M, Timpson NJ, Zabena C, Ingelsson E, An P, O'Connell J, Luan J, Elliott A, Roccasecca RM, Pattou F, Sethupathy P, Ariyurek Y, Barter P, Beilby JP, Ben Shlomo Y, Bergmann S, Bochud M, Bonnefond A, Borch Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Crisponi L, Day IN, de Geus EJ, Delplanque J, Fedson AC, Fischer Rosinsky A, Forouhi NG, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Grundy S, Gwilliam R, Hallmans G, Hammond N, Han X, Hartikainen AL, Hayward C, Heath SC, Hercberg S, Hicks AA, Hillman DR, Hingorani AD, Hui J, Hung J, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Mahley R, Mangino M, Manning AK, Martínez Larrad MT, McAteer JB, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Mukherjee S, Naitza S, Neville MJ, Oostra BA, Orrù M, Pakyz R, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rice K, Ripatti S, Rivadeneira F, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Seedorf U, Sharp SJ, Shields B, Sigurðsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Tönjes A, Uitterlinden AG, van Dijk KW, Varma D, Visvikis Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Ward KL, Watkins H, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano Ríos M, Lind L, Palmer LJ, Franks PW, Ebrahim S, Marmot M, Wright AF, Stumvoll M, Hamsten A, Buchanan TA, Valle TT, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Ferrucci L, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Barroso I., PAOLISSO, Giuseppe, Zhu, H, Shyh Chang, N, Segrè, Av, Shinoda, G, Shah, Sp, Einhorn, W, Takeuchi, A, Engreitz, Jm, Hagan, Jp, Kharas, Mg, Urbach, A, Thornton, Je, Triboulet, R, Gregory, Ri, Diagram, Consortium, Magic, Investigator, Altshuler, D, Voight BF, Daley G. Q., Scott, Lj, Steinthorsdottir, V, Morris, Ap, Dina, C, Welch, Rp, Zeggini, E, Huth, C, Aulchenko, Y, Thorleifsson, G, Mcculloch, Lj, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, Cj, Raychaudhuri, S, Mccarroll, Sa, Langenberg, C, Hofmann, Om, Dupuis, J, Qi, L, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Boström, Kb, Bravenboer, B, Bumpstead, S, Burtt, Np, Charpentier, G, Chines, P, Cornelis, M, Couper, Dj, Crawford, G, Doney, A, Elliott, K, Elliott, Al, Erdos, Mr, Fox, C, Franklin, C, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, Au, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Narisu, N, Nilsson, P, Owen, Kr, Payne, F, Perry, Jr, Petersen, Ak, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, Rayner, Nw, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Swift, Aj, Thorand, B, Tichet, J, Tuomi, T, van Dam, Rm, van Haeften, Tw, van Herpt, T, van Vliet Ostaptchouk, Jv, Walters, Gb, Weedon, Mn, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Collins, F, Gloyn, Al, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Laakso, M, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Walker, M, Wareham, Nj, Watanabe, Rm, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Meigs, Jb, Pankow, J, Pedersen, O, Wichmann, He, Barroso, I, Florez, Jc, Frayling, Tm, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Froguel, P, van Duijn, Cm, Stefansson, K, Boehnke, M, Mccarthy, Mi, Soranzo, N, Wheeler, E, Glazer, Nl, Bouatia Naji, N, Mägi, R, Randall, J, Johnson, T, Elliott, P, Rybin, D, Henneman, P, Dehghan, A, Hottenga, Jj, Song, K, Goel, A, Egan, Jm, Lajunen, T, Voight, Bf, Kanoni, S, Cavalcanti Proença, C, Kumari, M, Timpson, Nj, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J, Elliott, A, Roccasecca, Rm, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, Jp, Ben Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, Sj, Chen, Yd, Clarke, R, Coin, Lj, Cooper, Mn, Crisponi, L, Day, In, de Geus, Ej, Delplanque, J, Fedson, Ac, Fischer Rosinsky, A, Forouhi, Ng, Frants, R, Franzosi, Mg, Galan, P, Goodarzi, Mo, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, Al, Hayward, C, Heath, Sc, Hercberg, S, Hicks, Aa, Hillman, Dr, Hingorani, Ad, Hui, J, Hung, J, Jula, A, Kaakinen, M, Kaprio, J, Kesaniemi, Ya, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, Ko, Lathrop, Gm, Lawlor, Da, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Manning, Ak, Martínez Larrad, Mt, Mcateer, Jb, Mcpherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, Bd, Mukherjee, S, Naitza, S, Neville, Mj, Oostra, Ba, Orrù, M, Pakyz, R, Paolisso, Giuseppe, Pattaro, C, Pearson, D, Peden, Jf, Pedersen, Nl, Perola, M, Pfeiffer, Af, Pichler, I, Polasek, O, Posthuma, D, Potter, Sc, Pouta, A, Province, Ma, Psaty, Bm, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, Aa, Scheet, P, Seedorf, U, Sharp, Sj, Shields, B, Sigurðsson, G, Sijbrands, Ej, Silveira, A, Simpson, L, Singleton, A, Smith, Nl, Sovio, U, Swift, A, Syddall, H, Syvänen, Ac, Tanaka, T, Tönjes, A, Uitterlinden, Ag, van Dijk, Kw, Varma, D, Visvikis Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, Pj, Walley, A, Ward, Kl, Watkins, H, Wild, Sh, Willemsen, G, Witteman, Jc, Yarnell, Jw, Zelenika, D, Zethelius, B, Zhai, G, Zhao, Jh, Zillikens, Mc, Borecki, Ib, Loos, Rj, Meneton, P, Magnusson, Pk, Nathan, Dm, Williams, Gh, Silander, K, Salomaa, V, Smith, Gd, Bornstein, Sr, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, Ar, Cooper, C, Dedoussis, Gv, Serrano Ríos, M, Lind, L, Palmer, Lj, Franks, Pw, Ebrahim, S, Marmot, M, Wright, Af, Stumvoll, M, Hamsten, A, Buchanan, Ta, Valle, Tt, Rotter, Ji, Siscovick, D, Penninx, Bw, Boomsma, Di, Deloukas, P, Spector, Td, Ferrucci, L, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, Mr, Waterworth, Dm, Vollenweider, P, Peltonen, L, Mooser, V, and Barroso, I.
Published: 2011

46. Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes

Author: STRAWBRIDGE RJ, DUPUIS J, PROKOPENKO I, BARKER A, AHLQVIST E, RYBIN D, PETRIE JR, TRAVERS ME, BOUATIA-NAJI N, DIMAS AS, NICA A, WHEELER E, CHEN H, VOIGHT BF, TANEERA J, KANONI S, PEDEN JF, TURRINI F, GUSTAFSSON S, ZABENA C, ALMGREN P, BARKER DJ, BARNES D, DENNISON EM, ERIKSSON JG, ERIKSSON P, EURY E, FOLKERSEN L, FOX CS, FRAYLING TM, GOEL A, GU HF, HORIKOSHI M, ISOMAA B, JACKSON AU, JAMESON KA, KAJANTIE E, KERR-CONTE J, KUULASMAA T, KUUSISTO J, LOOS RJ, LUAN J, MAKRILAKIS K, MANNING AK, MARTÍNEZ-LARRAD MT, NARISU N, NASTASE MANNILA M, OHRVIK J, OSMOND C, PASCOE L, PAYNE F, SAYER AA, SENNBLAD B, SILVEIRA A, STANCÁKOVÁ A, STIRRUPS K, SWIFT AJ, SYVÄNEN AC, TUOMI T, VAN 'T HOOFT FM, WALKER M, WEEDON MN, XIE W, ZETHELIUS B, DIAGRAM CONSORTIUM, GIANT CONSORTIUM, MANUNTA P, MUTHER CONSORTIUM, CARDIOGRAM CONSORTIUM, C4D CONSORTIUM, ONGEN H, MÄLARSTIG A, HOPEWELL JC, SALEHEEN D, CHAMBERS J, PARISH S, DANESH J, KOONER J, OSTENSON CG, LIND L, COOPER CC, SERRANO-RÍOS M, FERRANNINI E, FORSEN TJ, CLARKE R, FRANZOSI MG, SEEDORF U, WATKINS H, FROGUEL P, JOHNSON P, DELOUKAS P, COLLINS FS, LAAKSO M, DERMITZAKIS ET, BOEHNKE M, MCCARTHY MI, WAREHAM NJ, GROOP L, PATTOU F, GLOYN AL, DEDOUSSIS GV, LYSSENKO V, MEIGS JB, BARROSO I, WATANABE RM, INGELSSON E, LANGENBERG C, HAMSTEN A, FLOREZ JC, Strawbridge, Rj, Dupuis, J, Prokopenko, I, Barker, A, Ahlqvist, E, Rybin, D, Petrie, Jr, Travers, Me, BOUATIA-NAJI, N, Dimas, A, Nica, A, Wheeler, E, Chen, H, Voight, Bf, Taneera, J, Kanoni, S, Peden, Jf, Turrini, F, Gustafsson, S, Zabena, C, Almgren, P, Barker, Dj, Barnes, D, Dennison, Em, Eriksson, Jg, Eriksson, P, Eury, E, Folkersen, L, Fox, C, Frayling, Tm, Goel, A, Gu, Hf, Horikoshi, M, Isomaa, B, Jackson, Au, Jameson, Ka, Kajantie, E, KERR-CONTE, J, Kuulasmaa, T, Kuusisto, J, Loos, Rj, Luan, J, Makrilakis, K, Manning, Ak, MARTÍNEZ-LARRAD, Mt, Narisu, N, NASTASE MANNILA, M, Ohrvik, J, Osmond, C, Pascoe, L, Payne, F, Sayer, Aa, Sennblad, B, Silveira, A, Stancáková, A, Stirrups, K, Swift, Aj, Syvänen, Ac, Tuomi, T, VAN 'T HOOFT, Fm, Walker, M, Weedon, Mn, Xie, W, Zethelius, B, Diagram, Consortium, Giant, Consortium, Manunta, P, Muther, Consortium, Cardiogram, Consortium, C4d, Consortium, Ongen, H, Mälarstig, A, Hopewell, Jc, Saleheen, D, Chambers, J, Parish, S, Danesh, J, Kooner, J, Ostenson, Cg, Lind, L, Cooper, Cc, SERRANO-RÍOS, M, Ferrannini, E, Forsen, Tj, Clarke, R, Franzosi, Mg, Seedorf, U, Watkins, H, Froguel, P, Johnson, P, Deloukas, P, Collins, F, Laakso, M, Dermitzakis, Et, Boehnke, M, Mccarthy, Mi, Wareham, Nj, Groop, L, Pattou, F, Gloyn, Al, Dedoussis, Gv, Lyssenko, V, Meigs, Jb, Barroso, I, Watanabe, Rm, Ingelsson, E, Langenberg, C, Hamsten, A, and Florez, Jc
Published: 2011

47. Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes

Author: Wood, AR, Tuke, MA, Nalls, M, Hernandez, D, Gibbs, JR, Lin, H, Xu, CS, Li, Q, Shen, J, Jun, G, Almeida, M, Tanaka, T, Perry, JR, Gaulton, K, Rivas, M, Pearson, R, Curran, JE, Johnson, MP, Göring, HH, Duggirala, R, Blangero, J, Mccarthy, MI, Bandinelli, S, Murray, A, Weedon, MN, Singleton, A, Melzer, D, Ferrucci, L, and Frayling, TM
Subjects: Adult, Genetic Markers, Male, Genotyping Techniques, Quantitative Trait Loci, and over, Medical and Health Sciences, Polymorphism, Single Nucleotide, Young Adult, Gene Frequency, 80 and over, Humans, Polymorphism, Genetic Association Studies, Aged, Genetics & Heredity, Aged, 80 and over, Genome, Genome, Human, Association Studies Articles, Genetic Variation, High-Throughput Nucleotide Sequencing, Single Nucleotide, Biological Sciences, Middle Aged, Phenotype, Female, Human
Abstract: Initial results from sequencing studies suggest that there are relatively few low-frequency (
Published: 2014

48. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study

Author: Vimaleswaran, KS, Cavadino, A, Berry, DJ, Jorde, R, Dieffenbach, AK, Lu, C, Alves, AC, Heerspink, HJL, Tikkanen, E, Eriksson, J, Wong, A, Mangino, M, Jablonski, KA, Nolte, IM, Houston, DK, Ahluwalia, TS, Van der Most, PJ, Pasko, D, Zgaga, L, Thiering, E, Vitart, V, Fraser, RM, Huffman, JE, De Boer, RA, Schoettker, B, Saum, K-U, McCarthy, MI, Dupuis, J, Herzig, K-H, Sebert, S, Pouta, A, Laitinen, J, Kleber, ME, Navis, G, Lorentzon, M, Jameson, K, Arden, N, Cooper, JA, Acharya, J, Hardy, R, Raitakari, O, Ripatti, S, Billings, LK, Lahti, J, Osmond, C, Penninx, BW, Rejnmark, L, Lohman, KK, Paternoster, L, Stolk, RP, Hernandez, DG, Byberg, L, Hagstrom, E, Melhus, H, Ingelsson, E, Mellstroem, D, Ljunggren, O, Tzoulaki, I, McLachlan, S, Theodoratou, E, Tiesler, CMT, Jula, A, Navarro, P, Wright, AF, Polasek, O, Hayward, C, Wilson, JF, Rudan, I, Salomaa, V, Heinrich, J, Campbell, H, Price, JF, Karlsson, M, Lind, L, Michaesson, K, Bandinelli, S, Frayling, TM, Hartman, CA, Sorensen, TIA, Kritchevsky, SB, Langdahl, BL, Eriksson, JG, Florez, JC, Spector, TD, Lehtimaki, T, Kuh, D, Humphries, SE, Cooper, C, Ohlsson, C, Maerz, W, De Borst, MH, Kumari, M, Kivimaki, M, Wang, TJ, Power, C, Brenner, H, Grimnes, G, Van der Harst, P, Snieder, H, Hingorani, AD, Pilz, S, Whittaker, JC, Jarvelin, M-R, and Hypponen, E
Subjects: Adult, Male, Caroline Hayward, D SUPPLEMENTATION, Oxidoreductases Acting on CH-CH Group Donors, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, Polymorphism, Single Nucleotide, DISEASE, Body Mass Index, 1117 Public Health and Health Services, Endocrinology & Metabolism, KIDNEY, GENETIC-VARIANTS, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Vitamin D, Cytochrome P450 Family 2, LifeLines Cohort Study investigators, Randomized Controlled Trials as Topic, OUTCOMES, Science & Technology, 1103 Clinical Sciences, Mendelian Randomization Analysis, Middle Aged, Vitamin D Deficiency, Phenotype, 1101 Medical Biochemistry and Metabolomics, Hypertension, Cholestanetriol 26-Monooxygenase, Global Blood Pressure Genetics (Global BPGen) consortium, TRIAL, Female, HEALTH, Life Sciences & Biomedicine, International Consortium for Blood Pressure (ICBP)
Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, −0·12 mm Hg, 95% CI −0·20 to −0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, −0·02 mm Hg, −0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of −0·10 mm Hg in systolic blood pressure (−0·21 to −0·0001; p=0·0498) and a change of −0·08 mm Hg in diastolic blood pressure (−0·15 to −0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of −0·29 mm Hg in diastolic blood pressure (−0·52 to −0·07; p=0·01), a change of −0·37 mm Hg in systolic blood pressure (−0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study. Funding British Heart Foundation, UK Medical Research Council, and Academy of Finland.
Published: 2014

49. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study

Author: Vimaleswaran, Kerani S., Cavadino, Alana, Berry, Diane J., Jorde, Rolf, Grimnes, Guri, Dieffenbach, Aida Karina, Lu, Chen, Alves, Alexessander Couto, Heerspink, Hiddo J. Lambers, Tikkanen, Emmi, Eriksson, Joel, Wong, Andrew, Mangino, Massimo, Jablonski, Kathleen A., Nolte, Ilja M., Houston, Denise K., Ahluwalia, Tarunveer Singh, van der Most, Peter J., Pasko, Dorota, Zgaga, Lina, Thiering, Elisabeth, Schöttker, B, Saum, KU, Brenner, H, Järvelin, MR, Tzoulaki, I, Snieder, H, Stolk, RP, Hartman, CA, de Boer, RA, van der Harst, P, Navis, G, de Borst, MH, Lorentzon, M, Mellström, D, Ohlsson, C, Hardy, R, Kuh, D, Cooper, JA, Acharya, J, Humphries, SE, Hingorani, AD, Kumari, M, Kivimaki, M, Spector, TD, Kritchevsky, SB, Lohman, KK, Sørensen, TIA, Frayling, TM, Campbell, H, Theodoratou, E, Fraser, RM, Wilson, JF, Rudan, I, Price, JF, McLachlan, S, Vitart, V, Navarro, P, Huffman, JE, Hayward, C, Wright, AF, Tiesler, CMT, Heinrich, J, McCarthy, MI, Ingelsson, E, Arden, N, Cooper, C, Dupuis, J, Herzig, KH, Sebert, S, Pouta, A, Laitinen, J, Kleber, ME, März, W, Jameson, K, Osmond, C, Raitakari, O, Ripatti, S, Lahti, J, Eriksson, JG, Penninx, BW, Billings, LK, Florez, JC, Rejnmark, L, Langdahl, BL, Paternoster, L, Hernandez, DG, Byberg, L, Michaelsson, K, Hagström, E, Melhus, H, Ljunggren, O, Lind, L, Jula, A, Polasek, O, Salomaa, V, Karlsson, M, Bandinelli, S, Lehtimäki, T, Wang, TJ, Pilz, S, and Whittaker, JC
Abstract: Background Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk. Methods In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that aff ect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium. Findings In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, –0·12 mm Hg, 95% CI –0·20 to –0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97–0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, –0·02 mm Hg, –0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of –0·10 mm Hg in systolic blood pressure (–0·21 to –0·0001; p=0·0498) and a change of –0·08 mm Hg in diastolic blood pressure (–0·15 to –0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96–0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of –0·29 mm Hg in diastolic blood pressure (–0·52 to –0·07; p=0·01), a change of –0·37 mm Hg in systolic blood pressure (–0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87–0·97; p=0·002). Interpretation Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This fi nding warrants further investigation in an independent, similarly powered study.
Published: 2014

50. New genetic loci link adipose and insulin biology to body fat distribution.

Author: ADIPOGen Consortium, CARDIOGRAMplusC4D Consortium, CKDGen Consortium, GEFOS Consortium, GENIE Consortium, International Endogene Consortium, LifeLines Cohort Study, MAGIC Investigators, MuTHER Consortium, PAGE Consortium, ReproGen Consortium, GLGC, ICBP, Dastani, Z., Hivert, MF., Timpson, N., Perry, JR., Yuan, X., Scott, RA., Henneman, P., Heid, IM., Kizer, JR., Lyytikainen, LP., Fuchsberger, C., Tanaka, T., Morris, AP., Small, K., Isaacs, A., Beekman, M., Coassin, S., Lohman, K., Qi, L., Kanoni, S., Pankow, JS., Uh, HW., Wu, Y., Bidulescu, A., Rasmussen-Torvik, LJ., Greenwood, CM., Ladouceur, M., Grimsby, J., Manning, AK., Liu, CT., Kooner, J., Mooser, VE., Vollenweider, P., Kapur, KA., Chambers, J., Wareham, NJ., Langenberg, C., Frants, R., Willemsvan-vanDijk, K., Oostra, BA., Willems, SM., Lamina, C., Winkler, T., Psaty, BM., Tracy, RP., Brody, J., Chen, I., Viikari, J., Kähönen, M., Pramstaller, PP., Evans, DM., St Pourcain, B., Sattar, N., Wood, A., Bandinelli, S., 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K.L.
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

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