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1. Asthma and obesity: endotoxin another insult to add to injury?

Author: Lad, N, Murphy, AM, Parenti, C, Nelson, CP, Williams, NC, Sharpe, GR, and McTernan, PG
Subjects: Diabetes & Metabolic Disorders, Inflammation, Immunology & Inflammation, Respiratory System, Prebiotic, General Medicine, Gut microbiota, lipopolysaccharides, Probiotic, Asthma, Diet, Gastrointestinal Microbiome, Endotoxins, Metabolism, Adipokines, Host-Microbe Interactions, Humans, Obesity, Review Articles
Abstract: Low-grade inflammation is often an underlying cause of several chronic diseases such as asthma, obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Defining the mediators of such chronic low-grade inflammation often appears dependent on which disease is being investigated. However, downstream systemic inflammatory cytokine responses in these diseases often overlap, noting there is no doubt more than one factor at play to heighten the inflammatory response. Furthermore, it is increasingly believed that diet and an altered gut microbiota may play an important role in the pathology of such diverse diseases. More specifically, the inflammatory mediator endotoxin, which is a complex lipopolysaccharide (LPS) derived from the outer membrane cell wall of Gram-negative bacteria and is abundant within the gut microbiota, and may play a direct role alongside inhaled allergens in eliciting an inflammatory response in asthma. Endotoxin has immunogenic effects and is sufficiently microscopic to traverse the gut mucosa and enter the systemic circulation to act as a mediator of chronic low-grade inflammation in disease. Whilst the role of endotoxin has been considered in conditions of obesity, cardiovascular disease and T2DM, endotoxin as an inflammatory trigger in asthma is less well understood. This review has sought to examine the current evidence for the role of endotoxin in asthma, and whether the gut microbiota could be a dietary target to improve disease management. This may expand our understanding of endotoxin as a mediator of further low-grade inflammatory diseases, and how endotoxin may represent yet another insult to add to injury.
Published: 2021

2. Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length

Author: Dempsey, PC, Musicha, C, Rowlands, AV, Davies, M, Khunti, K, Razieh, C, Timmins, I, Zaccardi, F, Codd, V, Nelson, CP, Yates, T, Samani, NJ, Dempsey, PC, Musicha, C, Rowlands, AV, Davies, M, Khunti, K, Razieh, C, Timmins, I, Zaccardi, F, Codd, V, Nelson, CP, Yates, T, and Samani, NJ
Abstract: Walking pace is a simple and functional form of movement and a strong predictor of health status, but the nature of its association with leucocyte telomere length (LTL) is unclear. Here we investigate whether walking pace is associated with LTL, which is causally associated with several chronic diseases and has been proposed as a marker of biological age. Analyses were conducted in 405,981 UK Biobank participants. We show that steady/average and brisk walkers had significantly longer LTL compared with slow walkers, with accelerometer-assessed measures of physical activity further supporting this through an association between LTL and habitual activity intensity, but not with total amount of activity. Bi-directional mendelian randomisation analyses suggest a causal link between walking pace and LTL, but not the other way around. A faster walking pace may be causally associated with longer LTL, which could help explain some of the beneficial effects of brisk walking on health status. Given its simple measurement and low heritability, self-reported walking pace may be a pragmatic target for interventions.
Published: 2022

3. Investigation of a UK biobank cohort reveals causal associations of self-reported walking pace with telomere length (vol 5, 381, 2022)

Author: Dempsey, PC, Musicha, C, Rowlands, AV, Davies, M, Khunti, K, Razieh, C, Timmins, I, Zaccardi, F, Codd, V, Nelson, CP, Yates, T, Samani, NJ, Dempsey, PC, Musicha, C, Rowlands, AV, Davies, M, Khunti, K, Razieh, C, Timmins, I, Zaccardi, F, Codd, V, Nelson, CP, Yates, T, and Samani, NJ
Published: 2022

4. 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

5. Measurement and initial characterization of leukocyte telomere length in 474,074 participants in UK Biobank

Author: Codd, V, Denniff, M, Swinfield, C, Warner, SC, Papakonstantinou, M, Sheth, S, Nanus, DE, Budgeon, CA, Musicha, C, Bountziouka, V, Wang, Q, Bramley, R, Allara, E, Kaptoge, S, Stoma, S, Jiang, T, Butterworth, AS, Wood, AM, Di Angelantonio, E, Thompson, Danesh, JN, Nelson, CP, Samani, NJ, Codd, V [0000-0002-9430-8254], Papakonstantinou, M [0000-0003-2664-9046], Budgeon, CA [0000-0002-1910-5561], Allara, E [0000-0002-1634-8330], Butterworth, AS [0000-0002-6915-9015], Thompson, JR [0000-0003-4819-1611], Samani, NJ [0000-0002-3286-8133], and Apollo - University of Cambridge Repository
Subjects: Male, Aging, Neuroscience (miscellaneous), Infant, Newborn, Ethnicity, Leukocytes, Humans, Female, Geriatrics and Gerontology, Telomere, United Kingdom, Biological Specimen Banks
Abstract: Leukocyte telomere length (LTL) is a proposed marker of biological age. Here we report the measurement and initial characterization of LTL in 474,074 participants in UK Biobank. We confirm that older age and male sex associate with shorter LTL, with women on average ~7 years younger in 'biological age' than men. Compared to white Europeans, LTL is markedly longer in African and Chinese ancestries. Older paternal age at birth is associated with longer individual LTL. Higher white cell count is associated with shorter LTL, but proportions of white cell subtypes show weaker associations. Age, ethnicity, sex and white cell count explain ~5.5% of LTL variance. Using paired samples from 1,351 participants taken ~5 years apart, we estimate the within-individual variability in LTL and provide a correction factor for this. This resource provides opportunities to investigate determinants and biomedical consequences of variation in LTL.
Published: 2022

6. Genetic predisposition to coronary artery disease in type 2 diabetes

Author: van Zuydam, NR, Ladenvall, C, Voight, BF, Strawbridge, RJ, Fernandez Tajes, J, Rayner, NW, Robertson, NR, Mahajan, A, Vlachopoulou, E, Goel, A, Kleber, ME, Nelson, CP, Kwee, LC, Esko, T, Mihailov, E, Mägi, R, Milani, L, Fischer, K, Kanoni, S, Kumar, J, Song, C, Hartiala, JA, Pedersen, NL, Perola, M, Gieger, C, Peters, A, Qu, L, Willems, SM, Doney, ASF, Morris, AD, Zheng, Y, Sesti, G, Hu, FB, Qi, L, Laakso, M, Thorsteinsdottir, U, Grallert, H, van Duijn, C, Reilly, MP, Ingelsson, E, Deloukas, P, Kathiresan, S, Metspalu, A, Shah, SH, Sinisalo, J, Salomaa, V, Hamsten, A, Samani, NJ, März, W, Hazen, SL, and Watkins, H
Abstract: Background - Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes (T2D). Methods - To test whether this reflects differential genetic influences on CAD-risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66,643 subjects (27,708 with CAD and 24,259 with T2D). Variants showing apparent association with CAD in stratified analyses and/or evidence of interaction were evaluated in a further 117,787 subjects (16,694 with CAD and 11,537 with T2D). Results - None of the previously characterised CAD loci was found to have specific effects on CAD in T2D individuals and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. Conclusions - This study found no evidence that the genetic architecture of CAD differs in those with T2D compared to those without T2D.
Published: 2020
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7. Sex differences in the risk of coronary heart disease associated with type 2 diabetes: A mendelian randomization analysis

Author: Peters, TM, Holmes, MV, Brent Richards, J, Palmer, T, Forgetta, V, Lindgren, CM, Asselbergs, FW, Nelson, CP, Samani, NJ, McCarthy, MI, Mahajan, A, Smith, GD, Woodward, M ; https://orcid.org/0000-0001-9800-5296, O’keeffe, LM, Peters, SAE ; https://orcid.org/0000-0003-0346-5412, Peters, TM, Holmes, MV, Brent Richards, J, Palmer, T, Forgetta, V, Lindgren, CM, Asselbergs, FW, Nelson, CP, Samani, NJ, McCarthy, MI, Mahajan, A, Smith, GD, Woodward, M ; https://orcid.org/0000-0001-9800-5296, O’keeffe, LM, and Peters, SAE ; https://orcid.org/0000-0003-0346-5412
Abstract: OBJECTIVE Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. RESEARCH DESIGN AND METHODS Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (251,420 women and 212,049 men). Weighted median, MR-Egger, MR-pleiotropy residual sum and outlier, and radial MR from summary-level analyses were used for pleiotropy assessment. RESULTS MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio 1.13 [95% CI 1.08–1.18] per 1-log unit increase in odds of type 2 diabetes) and men (1.21 [1.17–1.26] per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy; however, results were similar after correction for outlier SNPs. CONCLUSIONS This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.
Published: 2021

8. Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

Author: Hindy, G, Sun, L, Pennells, L, Kaptoge, S, Nelson, CP, Ritchie, SC, Abraham, G, Arnold, M, Bell, S, Bolton, T, Burgess, S, Dudbridge, F, Guo, Q, Sofianopoulou, E, Stevens, D, Thompson, JR, Butterworth, AS, Wood, A, Danesh, J, Samani, NJ, Inouye, M, Di Angelantonio, E, Hindy, G, Sun, L, Pennells, L, Kaptoge, S, Nelson, CP, Ritchie, SC, Abraham, G, Arnold, M, Bell, S, Bolton, T, Burgess, S, Dudbridge, F, Guo, Q, Sofianopoulou, E, Stevens, D, Thompson, JR, Butterworth, AS, Wood, A, Danesh, J, Samani, NJ, Inouye, M, and Di Angelantonio, E
Abstract: BACKGROUND: Polygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD. METHODS AND FINDINGS: Using data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703-0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009-0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40-75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted stra
Published: 2021

9. Targeted Workup after Initial Febrile Urinary Tract Infection: Using a Novel Machine Learning Model to Identify Children Most Likely to Benefit from Voiding Cystourethrogram

Author: Massachusetts Institute of Technology. Operations Research Center, Estrada, CR, Nelson, CP, Wang, HH, Bertsimas, Dimitris J, Dunn, Jack William, Li, Michael, Zhuo, Ying Daisy, MIT ORC Personalized Medicine Group, Advanced Analytics Group of Pediatric Urology, Massachusetts Institute of Technology. Operations Research Center, Estrada, CR, Nelson, CP, Wang, HH, Bertsimas, Dimitris J, Dunn, Jack William, Li, Michael, Zhuo, Ying Daisy, MIT ORC Personalized Medicine Group, and Advanced Analytics Group of Pediatric Urology
Abstract: Purpose:Significant debate persists regarding the appropriate workup in children with an initial urinary tract infection. Greatly preferable to all or none approaches in the current guideline would be a model to identify children at highest risk for a recurrent urinary tract infection plus vesicoureteral reflux to allow for targeted voiding cystourethrogram while children at low risk could be observed. We sought to develop a model to predict the probability of recurrent urinary tract infection associated vesicoureteral reflux in children after an initial urinary tract infection.Materials and Methods:We included subjects from the RIVUR (Randomized Intervention for Children with Vesico-Ureteral Reflux) and CUTIE (Careful Urinary Tract Infection Evaluation) trials in our study, excluding the prophylaxis treatment arm of the RIVUR. The main outcome was defined as recurrent urinary tract infection associated vesicoureteral reflux. Missing data were imputed using optimal tree imputation. Data were split into training, validation and testing sets. Machine learning algorithm hyperparameters were tuned by the validation set with fivefold cross-validation.Results:A total of 500 subjects, including 305 from the RIVUR and 195 from the CUTIE trials, were included in study. Of the subjects 90% were female and mean ± SD age was 21 ± 19 months. A recurrent urinary tract infection developed in 72 patients, of whom 53 also had vesicoureteral reflux (10.6% of the total). The final model included age, sex, race, weight, the systolic blood pressure percentile, dysuria, the urine albumin-to-creatinine ratio, prior antibiotic exposure and current medication. The model predicted recurrent urinary tract infection associated vesicoureteral reflux with an AUC of 0.761 (95% CI 0.714-0.808) in the testing set.Conclusions:Our predictive model using a novel machine learning algorithm provided promising performance to facilitate individualized treatment of children with an initial urinary tract in
Published: 2021

10. Targeted Workup after Initial Febrile Urinary Tract Infection: Using a Novel Machine Learning Model to Identify Children Most Likely to Benefit from Voiding Cystourethrogram

Author: Estrada, CR, Nelson, CP, Wang, HH, Bertsimas, Dimitris J, Dunn, Jack William, Li, Michael, Zhuo, Ying Daisy, MIT ORC Personalized Medicine Group, Advanced Analytics Group of Pediatric Urology, and Massachusetts Institute of Technology. Operations Research Center
Abstract: Purpose:Significant debate persists regarding the appropriate workup in children with an initial urinary tract infection. Greatly preferable to all or none approaches in the current guideline would be a model to identify children at highest risk for a recurrent urinary tract infection plus vesicoureteral reflux to allow for targeted voiding cystourethrogram while children at low risk could be observed. We sought to develop a model to predict the probability of recurrent urinary tract infection associated vesicoureteral reflux in children after an initial urinary tract infection.Materials and Methods:We included subjects from the RIVUR (Randomized Intervention for Children with Vesico-Ureteral Reflux) and CUTIE (Careful Urinary Tract Infection Evaluation) trials in our study, excluding the prophylaxis treatment arm of the RIVUR. The main outcome was defined as recurrent urinary tract infection associated vesicoureteral reflux. Missing data were imputed using optimal tree imputation. Data were split into training, validation and testing sets. Machine learning algorithm hyperparameters were tuned by the validation set with fivefold cross-validation.Results:A total of 500 subjects, including 305 from the RIVUR and 195 from the CUTIE trials, were included in study. Of the subjects 90% were female and mean ± SD age was 21 ± 19 months. A recurrent urinary tract infection developed in 72 patients, of whom 53 also had vesicoureteral reflux (10.6% of the total). The final model included age, sex, race, weight, the systolic blood pressure percentile, dysuria, the urine albumin-to-creatinine ratio, prior antibiotic exposure and current medication. The model predicted recurrent urinary tract infection associated vesicoureteral reflux with an AUC of 0.761 (95% CI 0.714-0.808) in the testing set.Conclusions:Our predictive model using a novel machine learning algorithm provided promising performance to facilitate individualized treatment of children with an initial urinary tract infection and identify those most likely to benefit from voiding cystourethrogram after the initial urinary tract infection. This would allow for more selective application of this test, increasing the yield while also minimizing overuse.
Published: 2019

11. Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length

Author: Li, C, Stoma, S, Lotta, LA, Warner, S, Albrecht, E, Allione, A, Arp, PP, Broer, L, Buxton, JL, Alves, ADSC, Deelen, J, Fedko, IO, Gordon, SD, Jiang, T, Karlsson, R, Kerrison, N, Loe, TK, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, JE, Amin, N, Beekman, M, Blakemore, A, Canzian, F, Hamby, SE, Hottenga, J-J, Jones, PD, Jousilahti, P, Magi, R, Medland, SE, Montgomery, GW, Nyholt, DR, Perola, M, Pietilainen, KH, Salomaa, V, Sillanpaa, E, Suchiman, HE, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, JG, Gunter, M, Hagg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, NG, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, NC, Nilsson, P, Ong, KK, Overvad, K, Palli, D, Panico, S, Pedersen, NL, Penninx, BWJH, Ramon Quiros, J, Riitta Jarvelin, M, Rodriguez-Barranco, M, Scott, RA, Severi, G, Slagboom, PE, Spector, TD, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, AG, van der Schouw, YT, van Duijn, CM, Weiderpass, E, Denchi, EL, Matullo, G, Butterworth, AS, Danesh, J, Samani, NJ, Wareham, NJ, Nelson, CP, Langenberg, C, Codd, V, Li, C, Stoma, S, Lotta, LA, Warner, S, Albrecht, E, Allione, A, Arp, PP, Broer, L, Buxton, JL, Alves, ADSC, Deelen, J, Fedko, IO, Gordon, SD, Jiang, T, Karlsson, R, Kerrison, N, Loe, TK, Mangino, M, Milaneschi, Y, Miraglio, B, Pervjakova, N, Russo, A, Surakka, I, van der Spek, A, Verhoeven, JE, Amin, N, Beekman, M, Blakemore, A, Canzian, F, Hamby, SE, Hottenga, J-J, Jones, PD, Jousilahti, P, Magi, R, Medland, SE, Montgomery, GW, Nyholt, DR, Perola, M, Pietilainen, KH, Salomaa, V, Sillanpaa, E, Suchiman, HE, van Heemst, D, Willemsen, G, Agudo, A, Boeing, H, Boomsma, D, Chirlaque, M-D, Fagherazzi, G, Ferrari, P, Franks, P, Gieger, C, Eriksson, JG, Gunter, M, Hagg, S, Hovatta, I, Imaz, L, Kaprio, J, Kaaks, R, Key, T, Krogh, V, Martin, NG, Melander, O, Metspalu, A, Moreno, C, Onland-Moret, NC, Nilsson, P, Ong, KK, Overvad, K, Palli, D, Panico, S, Pedersen, NL, Penninx, BWJH, Ramon Quiros, J, Riitta Jarvelin, M, Rodriguez-Barranco, M, Scott, RA, Severi, G, Slagboom, PE, Spector, TD, Tjonneland, A, Trichopoulou, A, Tumino, R, Uitterlinden, AG, van der Schouw, YT, van Duijn, CM, Weiderpass, E, Denchi, EL, Matullo, G, Butterworth, AS, Danesh, J, Samani, NJ, Wareham, NJ, Nelson, CP, Langenberg, C, and Codd, V
Abstract: Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.
Published: 2020

12. Exome Sequencing Analysis Identifies Rare Variants in ATM and RPL8 That Are Associated With Shorter Telomere Length

Author: van der Spek, Ashley, Warner, SC, Broer, Linda, Nelson, CP, Vojinovic, Dina, Ahmad, Shahzad, Arp, Pascal, Brouwer, Rutger, Denniff, M, Van den Hout - van Vroonhoven, Mirjam, van Rooij, Jeroen, Kraaij, Robert, van Ijcken, Wilfred, Samani, NJ, Ikram, Arfan, Uitterlinden, André, Codd, V, Amin, Najaf, Duijn, Cornelia, van der Spek, Ashley, Warner, SC, Broer, Linda, Nelson, CP, Vojinovic, Dina, Ahmad, Shahzad, Arp, Pascal, Brouwer, Rutger, Denniff, M, Van den Hout - van Vroonhoven, Mirjam, van Rooij, Jeroen, Kraaij, Robert, van Ijcken, Wilfred, Samani, NJ, Ikram, Arfan, Uitterlinden, André, Codd, V, Amin, Najaf, and Duijn, Cornelia
Published: 2020

13. Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events

Author: Patel, RS, Schmidt, AF, Tragante, V, McCubrey, RO, Holmes, MV, Howe, LJ, Direk, K, Åkerblom, A, Leander, K, Virani, SS, Kaminski, KA, Muehlschlegel, JD, Dubé, M-P, Allayee, H, Almgren, P, Alver, M, Baranova, EV, Behlouli, H, Boeckx, B, Braund, PS, Breitling, LP, Delgado, G, Duarte, NE, Dufresne, L, Eriksson, N, Foco, L, Gijsberts, CM, Gong, Y, Hartiala, J, Heydarpour, M, Hubacek, JA, Kleber, M, Kofink, D, Kuukasjärvi, P, Lee, V-V, Leiherer, A, Lenzini, PA, Levin, D, Lyytikäinen, L-P, Martinelli, N, Mons, U, Nelson, CP, Nikus, K, Pilbrow, AP, Ploski, R, Sun, YV, Tanck, MWT, Tang, WHW, Trompet, S, Van Der Laan, SW, Van Setten, J, Vilmundarson, RO, Anselmi, C, Vlachopoulou, E, Boerwinkle, E, Briguori, C, Carlquist, JF, Carruthers, KF, Casu, G, Deanfield, J, Deloukas, P, Dudbridge, F, Fitzpatrick, N, Gigante, B, James, S, Lokki, M-L, Lotufo, PA, Marziliano, N, Mordi, IR, Muhlestein, JB, Newton-Cheh, C, Pitha, J, Saely, CH, Samman-Tahhan, A, Sandesara, PB, Teren, A, Timmis, A, Van De Werf, F, Wauters, E, Wilde, AAM, Ford, I, Stott, DJ, Algra, A, Andreassi, MG, Ardissino, D, Arsenault, BJ, Ballantyne, CM, Bergmeijer, TO, Bezzina, CR, Body, SC, Bogaty, P, De Borst, GJ, Brenner, H, Burkhardt, R, Carpeggiani, C, Condorelli, G, Cooper-Dehoff, RM, Cresci, S, De Faire, U, Doughty, RN, Drexel, H, Engert, JC, Fox, KAA, Girelli, D, Hagström, E, Hazen, SL, Held, C, Hemingway, H, Hoefer, IE, Hovingh, GK, Johnson, JA, De Jong, PA, Jukema, JW, Kaczor, MP, Kähönen, M, Kettner, J, Kiliszek, M, Klungel, OH, Lagerqvist, B, Lambrechts, D, Laurikka, JO, Lehtimäki, T, Lindholm, D, Mahmoodi, BK, Der Zee, AH, McPherson, R, Melander, O, Metspalu, A, Pepinski, W, Olivieri, O, Opolski, G, Palmer, CN, Pasterkamp, G, Pepine, CJ, Pereira, AC, Pilote, L, Quyyumi, AA, Richards, AM, Sanak, M, Scholz, M, Siegbahn, A, Sinisalo, J, Smith, JG, Spertus, JA, Stewart, AFR, Szczeklik, W, Szpakowicz, A, Berg, JM, Thanassoulis, G, Thiery, J, Van Der Graaf, Y, Visseren, FLJ, Waltenberger, J, Van Der Harst, P, Tardif, J-C, Sattar, N, Lang, CC, Paré, G, Brophy, JM, Anderson, JL, März, W, Wallentin, L, Cameron, VA, Horne, BD, Samani, NJ, Hingorani, AD, and Asselbergs, FW
Subjects: Male, Myocardial Infarction, genetic risk factor, Coronary Artery Disease, Middle Aged, Article, chromosome 9p21, Gene Frequency, Risk Factors, Case-Control Studies, Odds Ratio, Humans, Female, Genetic Predisposition to Disease, cardiovascular diseases, Chromosomes, Human, Pair 9, secondary prevention
Abstract: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
Published: 2019

14. Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits (vol 50, pg 1412, 2018)

Author: Evangelou, E, Warren, HR, Mosen-Ansorena, D, Mifsud, B, Pazoki, R, Gao, H, Ntritsos, G, Dimou, N, Cabrera, CP, Karaman, I, Fu, LN, Evangelou, M, Witkowska, K, Tzanis, E, Hellwege, JN, Giri, A, Edwards, DRV, Sun, YV, Cho, K, Gaziano, JM, Wilson, PWF, Tsao, PS, Kovesdy, CP, Esko, T, Magi, R, Milani, L, Almgren, P, Boutin, T, Debette, S, Ding, J, Giulianini, F, Holliday, EG, Jackson, AU, Li-Gao, R, Lin, W-Y, Luan, J, Mangino, M, Oldmeadow, C, Prins, BP, Qian, Y, Sargurupremraj, M, Shah, N, Surendran, P, Theriault, S, Verweij, N, Willems, SM, Zhao, J-H, Amouyel, P, Connell, J, De Mutsert, R, Doney, ASF, Farrall, M, Menni, C, Morris, AD, Noordam, R, Pare, G, Poulter, NR, Shields, DC, Stanton, A, Thom, S, Abecasis, G, Amin, N, Arking, DE, Ayers, KL, Barbieri, CM, Batini, C, Bis, JC, Blake, T, Bochud, M, Boehnke, M, Boerwinkle, E, Boomsma, DI, Bottinger, EP, Braund, PS, Brumat, M, Campbell, A, Campbell, H, Chakravarti, A, Chambers, JC, Chauhan, G, Ciullo, M, Cocca, M, Collins, F, Cordell, HJ, Davies, G, De Borst, MH, De Geus, EJ, Deary, IJ, Deelen, J, Del Greco, FM, Demirkale, CY, Dorr, M, Ehret, GB, Elosua, R, Enroth, S, Erzurumluoglu, AM, Ferreira, T, Franberg, M, Franco, OH, Gandin, I, Gasparini, P, Giedraitis, V, Gieger, C, Girotto, G, Goel, A, Gow, AJ, Gudnason, V, Guo, X, Gyllensten, U, Hamsten, A, Harris, TB, Harris, SE, Hartman, CA, Havulinna, AS, Hicks, AA, Hofer, E, Hofman, A, Hottenga, J-J, Huffman, JE, Hwang, S-J, Ingelsson, E, James, A, Jansen, R, Jarvelin, M-R, Joehanes, R, Johansson, A, Johnson, AD, Joshi, PK, Jousilahti, P, Jukema, JW, Jula, A, Kahonen, M, Kathiresan, S, Keavney, BD, Khaw, K-T, Knekt, P, Knight, J, Kolcic, I, Kooner, JS, Koskinen, S, Kristiansson, K, Kutalik, Z, Laan, M, Larson, M, Launer, LJ, Lehne, B, Lehtimaki, T, Liewald, DCM, Lin, L, Lind, L, Lindgren, CM, Liu, Y, Loos, RJF, Lopez, LM, Lu, Y, Lyytikainen, L-P, Mahajan, A, Mamasoula, C, Marrugat, J, Marten, J, Milaneschi, Y, Morgan, A, Morris, AP, Morrison, AC, Munson, PJ, Nalls, MA, Nandakumar, P, Nelson, CP, Niiranen, T, Nolte, IM, Nutile, T, Oldehinkel, AJ, Oostra, BA, O'Reilly, PF, Org, E, Padmanabhan, S, Palmas, W, Palotie, A, Pattie, A, Penninx, BWJH, Perola, M, Peters, A, Polasek, O, Pramstaller, PP, Quang, TN, Raitakari, OT, Ren, M, Rettig, R, Rice, K, Ridker, PM, Ried, JS, Riese, H, Ripatti, S, Robino, A, Rose, LM, Rotter, JI, Rudan, I, Ruggiero, D, Saba, Y, Sala, CF, Salomaa, V, Samani, NJ, Sarin, A-P, Schmidt, R, Schmidt, H, Shrine, N, Siscovick, D, Smith, AV, Snieder, H, Sober, S, Sorice, R, Starr, JM, Stott, DJ, Strachan, DP, Strawbridge, RJ, Sundstrom, J, Swertz, MA, Taylor, KD, Teumer, A, Tobin, MD, Tomaszewski, M, Toniolo, D, Traglia, M, Trompet, S, Tuomilehto, J, Tzourio, C, Uitterlinden, AG, Vaez, A, Van der Most, PJ, Van Duijn, CM, Vergnaud, A-C, Verwoert, GC, Vitart, V, Volker, U, Vollenweider, P, Vuckovic, D, Watkins, H, Wild, SH, Willemsen, G, Wilson, JF, Wright, AF, Yao, J, Zemunik, T, Zhang, W, Attia, JR, Butterworth, AS, Chasman, DI, Conen, D, Cucca, F, Danesh, J, Hayward, C, Howson, JMM, Laakso, M, Lakatta, EG, Langenberg, C, Melander, O, Mook-Kanamori, DO, Palmer, CNA, Risch, L, Scott, RA, Scott, RJ, Sever, P, Spector, TD, Van der Harst, P, Wareham, NJ, Zeggini, E, Levy, D, Munroe, PB, Newton-Cheh, C, Brown, MJ, Metspalu, A, Hung, AM, O'Donnell, CJ, Edwards, TL, Psaty, BM, Tzoulaki, I, Barnes, MR, Wain, LV, Elliott, P, and Caulfield, MJ
Subjects: Genetics & Heredity, Science & Technology, Million Veteran Program, 06 Biological Sciences, Life Sciences & Biomedicine, 11 Medical and Health Sciences, Developmental Biology
Abstract: Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0205-x, published online 17 September 2018.
Published: 2018

15. Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity

Author: Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, Loos, RJF, Kilpelainen, TO, Bentley, AR, Noordam, R, Sung, YJ, Schwander, K, Winkler, TW, Jakupovic, H, Chasman, DI, Manning, A, Ntalla, I, Aschard, H, Brown, MR, de Las Fuentes, L, Franceschini, N, Guo, XQ, Vojinovic, Dina, Aslibekyan, S, Feitosa, MF, Kho, M, Musani, SK, Richard, M, Wang, HM, Wang, Z, Bartz, TM, Bielak, LF, Campbell, A (Archie), Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Li, CW, Lohman, KK, Marten, J, Sim, XL, Smith, AV, Tajuddin, S M, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Evangelou, E, Gao, C, Graff, M, Harris, SE, He, MA, Hsu, FC, Jackson, AU, Zhao, JH, Kraja, AT, Kuhnel, B, Laguzzi, F, Lyytikainen, LP, Nolte, IM, Rauramaa, R, Riaz, M, Robino, A, Rueedi, R, Stringham, HM, Takeuchi, F, van der Most, PJ, Varga, TV, Verweij, N, Ware, EB, Wen, WQ, Li, X Y, Yanek, LR, Amin, Najaf, Arnett, DK, Boerwinkle, E, Brumat, M, Cade, B, Canouil, M, Chen, YDI, Concas, MP, Connell, J, de Mutsert, R, de Silva, HJ, de Vries, PS, Demirkan, Ayse, Ding, JZ (Jing Zhong), Eaton, CB, Faul, JD, Friedlander, Y, Gabriel, KP, Ghanbari, Mohsen, Giulianini, F, Gu, CC, Gu, DF, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hunt, SC, Ikram, Arfan, Jonas, JB, Koh, WP, Komulainen, P, Krieger, JE, Kritchevsky, SB, Kutalik, Z, Kuusisto, J, Langefeld, CD, Langenberg, C, Launer, LJ, Leander, K, Lemaitre, RN, Lewis, CE, Liang, JJ, Alizadeh, BZ, Boezen, HM, Franke, L, Navis, G, Rots, M, Swertz, M, Wolffenbuttel, BHR, Wijmenga, C, Liu, JJ, Maagi, R, Manichaikul, A, Meitinger, T, Metspalu, A, Milaneschi, Y, Mohlke, KL, Mosley, TH, Murray, AD, Nalls, MA, Nang, EEK, Nelson, CP, Nona, S, Norris, JM, Nwuba, CV, O'Connell, J, Palmer, ND, Papanicolau, GJ, Pazoki, R, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, DJ, Poveda, A, Raitakari, OT, Rich, SS, Risch, N, Robinson, JG, Rose, LM, Rudan, I, Schreiner, PJ, Scott, RA, Sidney, SS, Sims, M, Smith, JA, Snieder, H, Sofer, T, Starr, JM, Sternfeld, B, Strauch, K, Tang, H, Taylor, KD, Tsai, MY, Tuomilehto, J, Uitterlinden, André, van der Ende, MY, van Heemst, D, Voortman, Trudy, Waldenberger, M, Wennberg, P, Wilson, G, Xiang, YB, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, de Faire, U, Deary, IJ, Elliott, P, Esko, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Kato, N, Laakso, M, Lakka, TA, Lehtimaki, T, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Samani, NJ, Shu, XO, van der Harst, P, van Vliet-Ostaptchouk, JV, Vollenweider, P, Wagenknecht, LE, Wang, YX, Wareham, NJ, Weir, DR, Wu, TC, Zheng, W, Zhu, XF, Evans, MK, Franks, PW, Gudnason, V, Hayward, C, Horta, BL, Kelly, TN, Liu, YM, North, KE, Pereira, AC, Ridker, PM, Tai, ES, van Dam, RM, Fox, ER, Kardia, SLR, Liu, CT, Mook, Dennis, Province, MA, Redline, S, Duijn, Cornelia, Rotter, JI, Kooperberg, CB, Gauderman, WJ, Psaty, BM, Rice, K, Munroe, PB, Fornage, M, Cupples, LA, Rotimi, CN, Morrison, AC, Rao, DC, and Loos, RJF
Published: 2019

16. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcus, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Maris, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pirastu, Nicola, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, McArdle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Toomas, Keis, Aime, Tammesoo, Mari-Liis, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Anders, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, James, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thomas, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Gasparini, Paolo, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andres, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willems, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van Duijn, Cornelia M. McEniery CM, Wilkinson IB, Cockcroft JR, O'Shaughnessy KM, Newhouse SJ, Yasmin, Smith AV, Eiriksdottir G, Launer LJ, Sigurdsson S, Aspelund T, Gudnason V, De Bacquer D, Rietzschel ER, De Backer GG, Van Bortel L, De Buyzere ML, Segers P, Bekaert S, Gillebert TC, De Meyer T, Ferrucci L, Tanaka T, Johnson AD, Levy D, Benjamin EJ, Mitchell GF, Vita JA, Larson MG, Hamburg NM, Vasan RS, Isaacs A, Schut AF, Oostra BA, van Duijn CM, van Rijn MJ, Sie MP, Newman AB, Herrington DM, Andrews JS, Ding J, Sutton-Tyrrell KC, Harris TB, Howard TD, Liu Y, Parsa A, Shuldiner AR, McArdle PF, Gibson Q, Post WS, Dehghan A, Hofman A, Uitterlinden AG, Sijbrands EJ, Rivadeneira F, Mattace-Raso FU, Verwoert GC, Witteman JC, Scuteri A, Lakatta EG, Jewell E, Abecasis GR, Tarasov KV, Uda M, Najjar SS, Sanna S, Attwood T, Belz S, Braund P, Cambien F, Cooper J, Crisp-Hihn A, Deloukas P, Foad N, Eardman J, Goodall AH, Gracey J, Gray E, Gulde S, Gwilliams R, Heimerl S, Hengstenberg C, Jolley J, Krishnan U, Linsel-Nitschke P, Lloyd-Jones H, Lugauer I, Lundmark P, Maouche S, Moore JS, Muir D, Murray E, Nelson CP, Neudert J, Niblett D, O'Leary K, Ouwehand WH, Pollard H, Rankin A, Rice CM, Sager H, Samani NJ, Sambrook J, Schmitz G, Scholz M, Schroeder L, Schunkert H, Syvannen AC, Wallace C, Kathiresan S, Reilly MP, Erdmann J, Assimes TL, Boerwinkle E, Hall A, 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, Voight BF, Wells GA, Assime TL, 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, Zeller T, Wild P, Schnabel R, Sinning C, Lackner K, Tiret L, Nicaud V, Bickel C, Rupprecht HJ, Perret C, Proust C, Münzel T, Barbalic M, Bis J, Chen IY, Cupples L, Demissie-Banjaw S, Folsom A, Glazer N, Harris T, Heckbert S, Lumley T, Marciante K, Morrison A, O' Donnell CJ, Psaty BM, Rice K, Rotter JI, Siscovick DS, Smith N, Smith A, Taylor KD, van Duijn C, Volcik K, Whitteman J, Ramachandran V, Uitterlinden A, Gretarsdottir S, Gulcher JR, Kong A, Stefansson K, Thorgeirsson G, Andersen K, Fischer M, Grosshennig A, Lieb W, Stark K, Schreiber S, Wichmann HE, Aherrahrou Z, Bruse P, Doering A, Illig T, Klopp N, Loley C, Medack A, Meisinger C, Meitinger T, Nahrstedt J, Peters A, Wagner AK, Willenborg C, Böhm BO, Dobnig H, Grammer TB, Hoffmann MM, Kleber M, März W, Meinitzer A, Winkelmann BR, Pilz S, Renner W, Scharnagl H, Stojakovic T, Tomaschitz A, Winkler K, Guiducci C, Burtt N, Gabriel SB, O'Donnell CJ, Elosua R, Peltonen L, Salomaa V, Schwartz SM, Melander O, Altshuler D, 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, Mooser V, Epstein SE, Rader DJ, Braund PS, Wright BJ, Balmforth AJ, Ball SG, Hall AS, Smith NL, Felix JF, Morrison AC, Demissie S, Glazer NL, Loehr LR, Rosamond WD, Bis JC, Folsom AR, Benjamin E, Aulchenko YS, Haritunians T, Couper D, Murabito J, Yang YA, Stricker BH, Gottdiener JS, Chang PP, Wang TJ, Rice KM, Heckbert SR, Fox ER, Willerson JT, Köttgen A, Pattaro C, Böger CA, Fuchsberger C, Olden M, Gao X, Yang Q, O'Connell JR, Schmidt H, Ketkar S, Hwang SJ, Teumer A, Paré G, Atkinson EJ, Lohman K, Cornelis MC, Probst-Hensch NM, Kronenberg F, Tönjes A, Hayward C, Rampersaud E, Mitchell BD, Arking DE, Struchalin M, Cavalieri M, Singleton A, Giallauria F, Metter J, de Boer IH, Siscovick D, Zillikens MC, Feitosa M, Province M, de Andrade M, Turner ST, Wild PS, Schnabel RB, Wilde S, Munzel TF, Leak TS, Koenig W, Zgaga L, Zemunik T, Kolcic I, Minelli C, Hu FB, Johansson A, Igl W, Zaboli G, Wild SH, Wright AF, Campbell H, Ellinghaus D, Imboden M, Nitsch D, Brandstätter A, Kollerits B, Kedenko L, Mägi R, Stumvoll M, Kovacs P, Boban M, Campbell S, Endlich K, Völzke H, Kroemer HK, Nauck M, Völker U, Polasek O, Vitart V, Badola S, Parker AN, Ridker PM, Kardia SL, Curhan GC, Franke A, Rochat T, Paulweber B, Prokopenko I, Wang W, Coresh J, Schmidt R, Shlipak MG, Borecki I, Krämer BK, Rudan I, Gyllensten U, Wilson JF, Pramstaller PP, Rettig R, Hastie N, Chasman DI, Kao WH, Heid IM, Fox CS, Felix SB, Watzinger N, Homuth G, Aragam J, Dörr M, Zweiker R, Lind L, Rodeheffer RJ, Greiser KH, Deckers JW, Stritzke J, Lackner KJ, Ingelsson E, Kullo I, Haerting J, Reffelmann T, Redfield MM, Werdan K, Arnett DK, Blettner M, Friedrich N, Chambers JC, Zhang W, Lord GM, van der Harst P, Lawlor DA, Sehmi JS, Gale DP, Wass MN, Ahmadi KR, Bakker SJ, Beckmann J, Bilo HJ, Bochud M, Brown MJ, Caulfield MJ, Connell JM, Cook HT, Cotlarciuc I, Davey Smith G, de Silva R, Deng G, Devuyst O, Dikkeschei LD, Dimkovic N, Dockrell M, Dominiczak A, Ebrahim S, Eggermann T, Farrall M, Floege J, Forouhi NG, Gansevoort RT, Han X, Hedblad B, Homan van der Heide JJ, Hepkema BG, Hernandez-Fuentes M, Hypponen E, Johnson T, de Jong PE, Kleefstra N, Lagou V, Lapsley M, Li Y, Loos RJ, Luan J, Luttropp K, Maréchal C, Munroe PB, Nordfors L, Penninx BW, Perucha E, Pouta A, Roderick PJ, Ruokonen A, Schalling M, Schlessinger D, Schlieper G, Seelen MA, Sjögren M, Smit JH, Snieder H, Soranzo N, Spector TD, Stenvinkel P, Sternberg MJ, Swaminathan R, Ubink-Veltmaat LJ, Vollenweider P, Waterworth D, Zerres K, Waeber G, Wareham NJ, Maxwell PH, McCarthy MI, Jarvelin MR, Lightstone L, Scott J, Navis G, Elliott P, Kooner JS., Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), University of Leicester, Department of Genetics [Leicester], Erasmus University Rotterdam, Netherlands Genomics Initiative, Department of Epidemiology and Biostatistics, School of Public Health, Zahedan University of Medical Sciences, Washington University in Saint Louis (WUSTL), Queen Mary University of London (QMUL), National Heart, Lung and Blood Institute, Partenaires INRAE, Centre Hospitalier Universitaire Vaudois (CHUV), Université de Lausanne = University of Lausanne (UNIL), Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Leiden University Medical Center (LUMC), Universiteit Leiden, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland [Reykjavik], Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Department of Epidemiology, The Netherlands Cancer Institute, Department of Mathematics, Boston University [Boston] (BU), GlaxoSmithKline, Division of Community Health Sciences, St. George's, University of South Florida [Tampa] (USF), Universität Greifswald - University of Greifswald, University of Washington [Seattle], University of Tartu, Institute of Molecular and Cell Biology, Medical Research Council, Institut de Génomique, Centre National de Génotypage, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University Medical Center Groningen, Department of Genetics, University Medical Center Groningen [Groningen] (UMCG), Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Massachusetts General Hospital [Boston], Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Università degli studi di Trieste = University of Trieste, Universität zu Lübeck = University of Lübeck [Lübeck], Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, The University of Western Australia (UWA), Department of Twin Research and Genetic Epidemiology, King's College London, London, University of Oxford, Medical University Graz, National Institute on Aging, Centre for population Health Sciences, University of Edinburgh, Uppsala University, Vrije Universiteit Amsterdam [Amsterdam] (VU), Western General Hospital, Harvard Medical School [Boston] (HMS), Brigham and Women's Hospital [Boston], University of Michigan System, University of Groningen, Ealing Hospital, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Medical Genetics Institute, Cedars-Sinai Medical Center, University of Tampere, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Split, The University of Texas Health Science Center at Houston (UTHealth), Johns Hopkins University (JHU), Netherlands Consortium for Healthy Aging [Leiden, Netherlands] (NCHA), National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Finnish Institute of Occupational Health, National Institute of Health and Welfare, University of Oulu, Lapland Central Hospital, University of Bristol [Bristol], Institute for Community Medicine, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), US National Institutes of Health, National Heart, Lung, and Blood Institute, European, Epidemiology, Internal Medicine, Public Health, Clinical Genetics, Université de Lausanne (UNIL), LeidenUniversity Medical Centre, University of Iceland, Università degli studi di Trieste, Universität zu Lübeck [Lübeck], University of Western Australia, University of Oxford [Oxford], VU University Amsterdam, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Human genetics, Psychiatry, EMGO - Mental health, NCA - Anxiety & Depression, Epidemiology and Data Science, Medical Research Council (MRC), Louise V., Wain, Germaine C., Verwoert, Paul F., O'Reilly, Gang, Shi, Toby, Johnson, Andrew D., Johnson, Murielle, Bochud, Kenneth M., Rice, Peter, Henneman, Albert V., Smith, Georg B., Ehret, Najaf, Amin, Martin G., Larson, Vincent, Mooser, David, Hadley, Marcus, Dörr, Joshua C., Bi, Thor, Aspelund, Tõnu, Esko, A. Cecile J. W., Janssen, Jing Hua, Zhao, Simon, Heath, Maris, Laan, Jingyuan, Fu, Giorgio, Pisti, Jian'An, Luan, Pankaj, Arora, Gavin, Luca, Pirastu, Nicola, Irene, Pichler, Anne U., Jackson, Rebecca J., Webster, Feng, Zhang, John F., Peden, Helena, Schmidt, Toshiko, Tanaka, Harry, Campbell, Wilmar, Igl, Yuri, Milaneschi, Jouke Jan, Hottenga, Veronique, Vitart, Daniel I., Chasman, Stella, Trompet, Jennifer L., Bragg Gresham, Behrooz Z., Alizadeh, John C., Chamber, Xiuqing, Guo, Terho, Lehtimäki, Brigitte, Kühnel, Lorna M., Lopez, Ozren, Polašek, Mladen, Boban, Christopher P., Nelson, Alanna C., Morrison, Vasyl, Pihur, Santhi K., Ganesh, Albert, Hofman, Suman, Kundu, Francesco U. S., Mattace Raso, Fernando, Rivadeneira, Eric J. G., Sijbrand, Andre G., Uitterlinden, Shih Jen, Hwang, Ramachandran S., Vasan, Thomas J., Wang, Sven, Bergmann, Peter, Vollenweider, Gérard, Waeber, Jaana, Laitinen, Anneli, Pouta, Paavo, Zitting, Wendy L., Mcardle, Heyo K., Kroemer, Uwe, Völker, Henry, Völzke, Nicole L., Glazer, Kent D., Taylor, Tamara B., Harri, Helene, Alavere, Toomas, Haller, Aime, Kei, Mari Liis, Tammesoo, Yurii, Aulchenko, Inês, Barroso, Kay Tee, Khaw, Pilar, Galan, Serge, Hercberg, Mark, Lathrop, Susana, Eyheramendy, Elin, Org, Siim, Sõber, Xiaowen, Lu, Ilja M., Nolte, Brenda W., Penninx, Tanguy, Corre, Corrado, Masciullo, Cinzia, Sala, Leif, Groop, Benjamin F., Voight, Olle, Melander, Christopher J., O'Donnell, Veikko, Salomaa, D'Adamo, ADAMO PIO, Antonella, Fabretto, Flavio, Faletra, Sheila, Ulivi, Fabiola Del Greco, M, Maurizio, Facheri, Francis S., Collin, Richard N., Bergman, John P., Beilby, Joseph, Hung, A., William Musk, Massimo, Mangino, So Youn, Shin, Nicole, Soranzo, Hugh, Watkin, Anuj, Goel, Anders, Hamsten, Pierre, Gider, Marisa, Loitfelder, Marion, Zeginigg, Dena, Hernandez, Samer S., Najjar, Pau, Navarro, Sarah H., Wild, Anna Maria, Corsi, Andrew, Singleton, Eco J. C., de Geu, Gonneke, Willemsen, Alex N., Parker, Lynda M., Rose, Brendan, Buckley, David, Stott, Marco, Orru, Manuela, Uda, Melanie M., van der Klauw, Weihua, Zhang, Xinzhong, Li, James, Scott, Yii Der Ida, Chen, Gregory L., Burke, Mika, Kähönen, Jorma, Viikari, Angela, Döring, Thomas, Meitinger, Gail, Davie, John M., Starr, Valur, Emilsson, Andrew, Plump, Jan H., Lindeman, Peter A. C., 't Hoen, Inke R., König, Janine F., Felix, Robert, Clarke, Jemma C., Hopewell, Halit, Ongen, Monique, Breteler, Stéphanie, Debette, Anita L., Destefano, Myriam, Fornage, Gary F., Mitchell, Nicholas L., Smith, Hilma, Holm, Kari, Stefansson, Gudmar, Thorleifsson, Unnur, Thorsteinsdottir, Nilesh J., Samani, Michael, Preu, Igor, Rudan, Caroline, Hayward, Ian J., Deary, H., Erich Wichmann, Olli T., Raitakari, Walter, Palma, Jaspal S., Kooner, Ronald P., Stolk, J., Wouter Jukema, Alan F., Wright, Dorret I., Boomsma, Stefania, Bandinelli, Ulf B., Gyllensten, James F., Wilson, Luigi, Ferrucci, Reinhold, Schmidt, Martin, Farrall, Tim D., Spector, Lyle J., Palmer, Jaakko, Tuomilehto, Arne, Pfeufer, Gasparini, Paolo, David, Siscovick, David, Altshuler, Ruth J. F., Loo, Daniela, Toniolo, Harold, Snieder, Christian, Gieger, Pierre, Meneton, Nicholas J., Wareham, Ben A., Oostra, Andres, Metspalu, Lenore, Launer, Rainer, Rettig, David P., Strachan, Jacques S., Beckmann, Jacqueline C. M., Witteman, Jeanette, Erdmann, Ko Willems van, Dijk, Eric, Boerwinkle, Michael, Boehnke, Paul M., Ridker, Marjo Riitta, Jarvelin, Aravinda, Chakravarti, Goncalo R., Abecasi, Vilmundur, Gudnason, Christopher Newton, Cheh, Daniel, Levy, Patricia B., Munroe, Bruce M., Psaty, Mark J., Caulfield, Dabeeru C., Rao, Martin D., Tobin, Paul, Elliott, Cornelia M., van Duijn, Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Wain, Louise V., Verwoert, Germaine C., O'Reilly, Paul F., Shi, Gang, Johnson, Toby, Johnson, Andrew D., Bochud, Murielle, Rice, Kenneth M., Henneman, Peter, Smith, Albert V., Ehret, Georg B., Amin, Najaf, Larson, Martin G., Mooser, Vincent, Hadley, David, Dörr, Marcu, Bis, Joshua C, Aspelund, Thor, Esko, Tõnu, Janssens, A Cecile J. W., Zhao, Jing Hua, Heath, Simon, Laan, Mari, Fu, Jingyuan, Pistis, Giorgio, Luan, Jian'An, Arora, Pankaj, Lucas, Gavin, Pichler, Irene, Jackson, Anne U., Webster, Rebecca J., Zhang, Feng, Peden, John F., Schmidt, Helena, Tanaka, Toshiko, Campbell, Harry, Igl, Wilmar, Milaneschi, Yuri, Hottenga, Jouke-Jan, Vitart, Veronique, Chasman, Daniel I., Trompet, Stella, Bragg-Gresham, Jennifer L., Alizadeh, Behrooz Z., Chambers, John C., Guo, Xiuqing, Lehtimäki, Terho, Kühnel, Brigitte, Lopez, Lorna M., Polašek, Ozren, Boban, Mladen, Nelson, Christopher P., Morrison, Alanna C., Pihur, Vasyl, Ganesh, Santhi K., Hofman, Albert, Kundu, Suman, Mattace-Raso, Francesco U. S., Rivadeneira, Fernando, Sijbrands, Eric J. G., Uitterlinden, Andre G., Hwang, Shih-Jen, Vasan, Ramachandran S., Wang, Thomas J., Bergmann, Sven, Vollenweider, Peter, Waeber, Gérard, Laitinen, Jaana, Pouta, Anneli, Zitting, Paavo, Mcardle, Wendy L., Kroemer, Heyo K., Völker, Uwe, Völzke, Henry, Glazer, Nicole L., Taylor, Kent D., Harris, Tamara B., Alavere, Helene, Haller, Tooma, Keis, Aime, Tammesoo, Mari-Lii, Aulchenko, Yurii, Barroso, In S., Khaw, Kay-Tee, Galan, Pilar, Hercberg, Serge, Lathrop, Mark, Eyheramendy, Susana, Org, Elin, Sõber, Siim, Lu, Xiaowen, Nolte, Ilja M., Penninx, Brenda W., Corre, Tanguy, Masciullo, Corrado, Sala, Cinzia, Groop, Leif, Voight, Benjamin F, Melander, Olle, O'Donnell, Christopher J, Salomaa, Veikko, D'Adamo, Adamo Pio, Fabretto, Antonella, Faletra, Flavio, Ulivi, Sheila, Del Greco M, Fabiola, Facheris, Maurizio, Collins, Francis S., Bergman, Richard N., Beilby, John P., Hung, Joseph, Musk, A William, Mangino, Massimo, Shin, So-Youn, Soranzo, Nicole, Watkins, Hugh, Goel, Anuj, Hamsten, Ander, Gider, Pierre, Loitfelder, Marisa, Zeginigg, Marion, Hernandez, Dena, Najjar, Samer S., Navarro, Pau, Wild, Sarah H., Corsi, Anna Maria, Singleton, Andrew, De Geus, Eco J. C., Willemsen, Gonneke, Parker, Alex N., Rose, Lynda M., Buckley, Brendan, Stott, David, Orru, Marco, Uda, Manuela, Van Der Klauw, Melanie M., Zhang, Weihua, Li, Xinzhong, Scott, Jame, Chen, Yii-Der Ida, Burke, Gregory L, Kähönen, Mika, Viikari, Jorma, Döring, Angela, Meitinger, Thoma, Davies, Gail, Starr, John M., Emilsson, Valur, Plump, Andrew, Lindeman, Jan H., Hoen, Peter A. C. T., König, Inke R., Felix, Janine F., Clarke, Robert, Hopewell, Jemma C., Ongen, Halit, Breteler, Monique, Debette, Stéphanie, Destefano, Anita L., Fornage, Myriam, Mitchell, Gary F., Smith, Nicholas L., Holm, Hilma, Stefansson, Kari, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Samani, Nilesh J., Preuss, Michael, Rudan, Igor, Hayward, Caroline, Deary, Ian J., Wichmann, H-Erich, Raitakari, Olli T., Palmas, Walter, Kooner, Jaspal S., Stolk, Ronald P., Jukema, J Wouter, Wright, Alan F., Boomsma, Dorret I., Bandinelli, Stefania, Gyllensten, Ulf B., Wilson, James F., Ferrucci, Luigi, Schmidt, Reinhold, Farrall, Martin, Spector, Tim D., Palmer, Lyle J., Tuomilehto, Jaakko, Pfeufer, Arne, Siscovick, David, Altshuler, David, Loos, Ruth J. F., Toniolo, Daniela, Snieder, Harold, Gieger, Christian, Meneton, Pierre, Wareham, Nicholas J., Oostra, Ben A., Metspalu, Andre, Launer, Lenore, Rettig, Rainer, Strachan, David P., Beckmann, Jacques S., Witteman, Jacqueline C. M., Erdmann, Jeanette, Van Dijk, Ko Willem, Boerwinkle, Eric, Boehnke, Michael, Ridker, Paul M., Jarvelin, Marjo-Riitta, Chakravarti, Aravinda, Abecasis, Goncalo R., Gudnason, Vilmundur, Newton-Cheh, Christopher, Levy, Daniel, Munroe, Patricia B., Psaty, Bruce M., Caulfield, Mark J., Rao, Dabeeru C., Tobin, Martin D., Elliott, Paul, Van, Duijn, Cornelia M., McEniery CM, Wilkinson, Ib, Cockcroft, Jr, O'Shaughnessy, Km, Newhouse, Sj, Yasmin, Smith, Av, Eiriksdottir, G, Launer, Lj, Sigurdsson, S, Aspelund, T, Gudnason, V, De Bacquer, D, Rietzschel, Er, De Backer, Gg, Van Bortel, L, De Buyzere, Ml, Segers, P, Bekaert, S, Gillebert, Tc, De Meyer, T, Ferrucci, L, Tanaka, T, Johnson, Ad, Levy, D, Benjamin, Ej, Mitchell, Gf, Vita, Ja, Larson, Mg, Hamburg, Nm, Vasan, R, Isaacs, A, Schut, Af, Oostra, Ba, van Duijn, Cm, van Rijn, Mj, Sie, Mp, Newman, Ab, Herrington, Dm, Andrews, J, Ding, J, Sutton-Tyrrell, Kc, Harris, Tb, Howard, Td, Liu, Y, Parsa, A, Shuldiner, Ar, Mcardle, Pf, Gibson, Q, Post, W, Dehghan, A, Hofman, A, Uitterlinden, Ag, Sijbrands, Ej, Rivadeneira, F, Mattace-Raso, Fu, Verwoert, Gc, Witteman, Jc, Scuteri, A, Lakatta, Eg, Jewell, E, Abecasis, Gr, Tarasov, Kv, Uda, M, Najjar, S, Sanna, S, Attwood, T, Belz, S, Braund, P, Cambien, F, Cooper, J, Crisp-Hihn, A, Deloukas, P, Foad, N, Eardman, J, Goodall, Ah, Gracey, J, Gray, E, Gulde, S, Gwilliams, R, Heimerl, S, Hengstenberg, C, Jolley, J, Krishnan, U, Linsel-Nitschke, P, Lloyd-Jones, H, Lugauer, I, Lundmark, P, Maouche, S, Moore, J, Muir, D, Murray, E, Nelson, Cp, Neudert, J, Niblett, D, O'Leary, K, Ouwehand, Wh, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Samani, Nj, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Schunkert, H, Syvannen, Ac, Wallace, C, Kathiresan, S, Reilly, Mp, Erdmann, J, Assimes, Tl, Boerwinkle, E, Hall, A, 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, Voight, Bf, Wells, Ga, Assime, Tl, 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, Zeller, T, Wild, P, Schnabel, R, Sinning, C, Lackner, K, Tiret, L, Nicaud, V, Bickel, C, Rupprecht, Hj, Perret, C, Proust, C, Münzel, T, Barbalic, M, Bis, J, Chen, Iy, Cupples, L, Demissie-Banjaw, S, Folsom, A, Glazer, N, Harris, T, Heckbert, S, Lumley, T, Marciante, K, Morrison, A, O' Donnell, Cj, Psaty, Bm, Rice, K, Rotter, Ji, Siscovick, D, Smith, N, Smith, A, Taylor, Kd, van Duijn, C, Volcik, K, Whitteman, J, Ramachandran, V, Uitterlinden, A, Gretarsdottir, S, Gulcher, Jr, Kong, A, Stefansson, K, Thorgeirsson, G, Andersen, K, Fischer, M, Grosshennig, A, Lieb, W, Stark, K, Schreiber, S, Wichmann, He, Aherrahrou, Z, Bruse, P, Doering, A, Illig, T, Klopp, N, Loley, C, Medack, A, Meisinger, C, Meitinger, T, Nahrstedt, J, Peters, A, Wagner, Ak, Willenborg, C, Böhm, Bo, Dobnig, H, Grammer, Tb, Hoffmann, Mm, Kleber, M, März, W, Meinitzer, A, Winkelmann, Br, Pilz, S, Renner, W, Scharnagl, H, Stojakovic, T, Tomaschitz, A, Winkler, K, Guiducci, C, Burtt, N, Gabriel, Sb, O'Donnell, Cj, Elosua, R, Peltonen, L, Salomaa, V, Schwartz, Sm, Melander, O, Altshuler, D, Dandona, S, Jarinova, O, Qu, L, Wilensky, R, Matthai, W, Hakonarson, Hh, Devaney, J, Burnett, M, Pichard, Ad, Kent, Km, Satler, L, Lindsay, Jm, Waksman, R, Knouff, Cw, Waterworth, Dm, Walker, Mc, Mooser, V, Epstein, Se, Rader, Dj, Wright, Bj, Balmforth, Aj, Ball, Sg, Smith, Nl, Felix, Jf, Morrison, Ac, Demissie, S, Glazer, Nl, Loehr, Lr, Rosamond, Wd, Bis, Jc, Folsom, Ar, Benjamin, E, Aulchenko, Y, Haritunians, T, Couper, D, Murabito, J, Yang, Ya, Stricker, Bh, Gottdiener, J, Chang, Pp, Wang, Tj, Rice, Km, Heckbert, Sr, Fox, Er, Willerson, Jt, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Gao, X, Yang, Q, O'Connell, Jr, Schmidt, H, Ketkar, S, Hwang, Sj, Teumer, A, Paré, G, Atkinson, Ej, Lohman, K, Cornelis, Mc, Probst-Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Rampersaud, E, Mitchell, Bd, Arking, De, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Zillikens, Mc, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, A, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Prokopenko, I, Wang, W, Coresh, J, Schmidt, R, Shlipak, Mg, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Felix, Sb, Watzinger, N, Homuth, G, Aragam, J, Dörr, M, Zweiker, R, Lind, L, Rodeheffer, Rj, Greiser, Kh, Deckers, Jw, Stritzke, J, Lackner, Kj, Ingelsson, E, Kullo, I, Haerting, J, Reffelmann, T, Redfield, Mm, Werdan, K, Arnett, Dk, Blettner, M, Friedrich, N, Chambers, Jc, Zhang, W, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Davey Smith, G, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, Homan van der Heide, Jj, Hepkema, Bg, Hernandez-Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Munroe, Pb, Nordfors, L, Penninx, Bw, Perucha, E, Pouta, A, Roderick, Pj, Ruokonen, A, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink-Veltmaat, Lj, Vollenweider, P, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Lightstone, L, Scott, J, Navis, G, Elliott, P, and Kooner, Js.
Subjects: Netherlands Twin Register (NTR), Linkage disequilibrium, pulse pressure, mean arterial pressure, genome-wide, [SDV]Life Sciences [q-bio], Genome-wide association study, BLOOD-PRESSURE, Blood Pressure, 030204 cardiovascular system & hematology, Linkage Disequilibrium, 0302 clinical medicine, RELEVANCE, CardioGram, Medicine and Health Sciences, Genetics & Heredity, ddc:616, Genetics, 0303 health sciences, Genome-wide association, 11 Medical And Health Sciences, Arteries, ADRENERGIC-RECEPTOR TRAFFICKING, Pulse pressure, EchoGen consortium, Hypertension, HEART-FAILURE, arterial pressure, Case-Control Studie, Life Sciences & Biomedicine, Human, circulatory and respiratory physiology, medicine.medical_specialty, Mean arterial pressure, Arterie, AortaGen Consortium, Cardiogenics consortium, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Humans, cardiovascular diseases, METAANALYSIS, 030304 developmental biology, Genetic association, Science & Technology, HYPERTENSION, MORTALITY, Case-control study, CARDIOVASCULAR-DISEASE RISK, 06 Biological Sciences, GENE, MICE, Endocrinology, Blood pressure, CKDGen consortium, Genetic Loci, Case-Control Studies, KidneyGen consortium, CHARGE Consortium Heart Failure Working Group, LifeLines Cohort Study, Developmental Biology, Follow-Up Studies, Genome-Wide Association Study
Abstract: Les affiliations des 100 premiers auteurs sont renseignées dans la notice. Les affiliations des autres auteurs sont disponibles à la fin de la publication.; International audience; Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.
Published: 2016
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17. 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

18. 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

19. Discovery of novel heart rate-associated loci using the Exome Chip

Author: van den Berg, ME, Warren, HR, Cabrera, CP, Verweij, N, Mifsud, B, Haessler, J, Bihlmeyer, NA, Fu, YP, Weiss, S, Lin, HJ, Grarup, N, Li-Gao, R, Pistis, G, Shah, N, Brody, JA, Müller-Nurasyid, M, Lin, H, Mei, H, Smith, AV, Lyytikäinen, LP, Hall, LM, van Setten, J, Trompet, S, Prins, BP, Isaacs, A, Radmanesh, F, Marten, J, Entwistle, A, Kors, JA, Silva, CT, Alonso, A, Bis, JC, de Boer, R, de Haan, HG, de Mutsert, R, Dedoussis, G, Dominiczak, AF, Doney, ASF, Ellinor, PT, Eppinga, RN, Felix, SB, Guo, X, Hagemeijer, Y, Hansen, T, Harris, TB, Heckbert, SR, Huang, PL, Hwang, SJ, Kähönen, M, Kanters, JK, Kolcic, I, Launer, LJ, Li, M, Yao, J, Linneberg, A, Liu, S, Macfarlane, PW, Mangino, M, Morris, AD, Mulas, A, Murray, AD, Nelson, CP, Orrú, M, Padmanabhan, S, Peters, A, Porteous, DJ, Poulter, N, Psaty, BM, Qi, L, Raitakari, OT, Rivadeneira, F, Roselli, C, and Rudan, I
Abstract: © The Author 2017. Published by Oxford University Press. Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses.Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies.
Published: 2017
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20. Genomic Risk Prediction of Coronary Artery Disease in 480,000 Adults Implications for Primary Prevention

Author: Inouye, M, Abraham, G, Nelson, CP, Wood, AM, Sweeting, MJ, Dudbridge, F, Lai, FY, Kaptoge, S, Brozynska, M, Wang, T, Ye, S, Webb, TR, Rutter, MK, Tzoulaki, I, Patel, RS, Loos, RJF, Keavney, B, Hemingway, H, Thompson, J, Watkins, H, Deloukas, P, Di Angelantonio, E, Butterworth, AS, Danesh, J, Samani, NJ, Inouye, M, Abraham, G, Nelson, CP, Wood, AM, Sweeting, MJ, Dudbridge, F, Lai, FY, Kaptoge, S, Brozynska, M, Wang, T, Ye, S, Webb, TR, Rutter, MK, Tzoulaki, I, Patel, RS, Loos, RJF, Keavney, B, Hemingway, H, Thompson, J, Watkins, H, Deloukas, P, Di Angelantonio, E, Butterworth, AS, Danesh, J, and Samani, NJ
Abstract: BACKGROUND: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes. OBJECTIVES: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention. METHODS: Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank. RESULTS: The hazard ratio (HR) for CAD was 1.71 (95% confidence interval [CI]: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age. CONCLUSIONS: The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screeni
Published: 2018

21. Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Author: Prins, BP, Mead, TJ, Brody, JA, Sveinbjornsson, G, Ntalla, I, Bihlmeyer, NA, van den Berg, Marten, Bork-Jensen, J, Cappellani, S, Van Duijvenboden, S, Klena, NT, Gabriel, GC, Liu, XQ, Gulec, C, Grarup, N, Haessler, J, Hall, LM, Iorio, A, Isaacs, Aaron, Li-Gao, RF, Lin, HH, Liu, CT, Lyytikainen, LP, Marten, J, Mei, H, Muller-Nurasyid, M, Orini, M, Padmanabhan, S, Radmanesh, F, Ramirez, J, Robino, A, Schwartz, M, van Setten, J, Smith, AV, Verweij, N, Warren, HR, Weiss, S, Alonso, A, Arnar, DO, Bots, ML, de Boer, RA, Dominiczak, AF, Eijgelsheim, Mark, Ellinor, PT, Guo, XQ, Felix, SB, Harris, TB, Hayward, C, Heckbert, SR, Huang, PL, Jukema, JW, Kahonen, M, Kors, Jan, Lambiase, PD, Launer, LJ, Li, M, Linneberg, A, Nelson, CP, Pedersen, O, Perez, M, Peters, A, Polasek, O, Psaty, BM, Raitakari, OT, Rice, KM, Rotter, JI, Sinner, MF, Soliman, EZ, Spector, TD, Strauch, K, Thorsteinsdottir, U, Tinker, A, Trompet, S, Uitterlinden, André, Vaartjes, I, Meer, P, Volker, U, Volzke, H, Waldenberger, M, Wilson, JG, Xie, ZJ, Asselbergs, FW, Dorr, M, Duijn, Cornelia, Gasparini, P, Gudbjartsson, DF, Gudnason, V, Hansen, T, Kaab, S, Kanters, JK, Kooperberg, C, Lehtimaki, T, Lin, H J, Lubitz, SA, Mook, Dennis, Conti, FJ, Newton-Cheh, CH, Rosand, J, Rudan, I, Samani, NJ, Sinagra, G, Smith, BH, Holm, H, Stricker, Bruno, Ulivi, S, Sotoodehnia, N, Apte, SS, van der Harst, P, Stefansson, K, Munroe, PB, Arking, DE, Lo, CW, Jamshidi, Y, Prins, BP, Mead, TJ, Brody, JA, Sveinbjornsson, G, Ntalla, I, Bihlmeyer, NA, van den Berg, Marten, Bork-Jensen, J, Cappellani, S, Van Duijvenboden, S, Klena, NT, Gabriel, GC, Liu, XQ, Gulec, C, Grarup, N, Haessler, J, Hall, LM, Iorio, A, Isaacs, Aaron, Li-Gao, RF, Lin, HH, Liu, CT, Lyytikainen, LP, Marten, J, Mei, H, Muller-Nurasyid, M, Orini, M, Padmanabhan, S, Radmanesh, F, Ramirez, J, Robino, A, Schwartz, M, van Setten, J, Smith, AV, Verweij, N, Warren, HR, Weiss, S, Alonso, A, Arnar, DO, Bots, ML, de Boer, RA, Dominiczak, AF, Eijgelsheim, Mark, Ellinor, PT, Guo, XQ, Felix, SB, Harris, TB, Hayward, C, Heckbert, SR, Huang, PL, Jukema, JW, Kahonen, M, Kors, Jan, Lambiase, PD, Launer, LJ, Li, M, Linneberg, A, Nelson, CP, Pedersen, O, Perez, M, Peters, A, Polasek, O, Psaty, BM, Raitakari, OT, Rice, KM, Rotter, JI, Sinner, MF, Soliman, EZ, Spector, TD, Strauch, K, Thorsteinsdottir, U, Tinker, A, Trompet, S, Uitterlinden, André, Vaartjes, I, Meer, P, Volker, U, Volzke, H, Waldenberger, M, Wilson, JG, Xie, ZJ, Asselbergs, FW, Dorr, M, Duijn, Cornelia, Gasparini, P, Gudbjartsson, DF, Gudnason, V, Hansen, T, Kaab, S, Kanters, JK, Kooperberg, C, Lehtimaki, T, Lin, H J, Lubitz, SA, Mook, Dennis, Conti, FJ, Newton-Cheh, CH, Rosand, J, Rudan, I, Samani, NJ, Sinagra, G, Smith, BH, Holm, H, Stricker, Bruno, Ulivi, S, Sotoodehnia, N, Apte, SS, van der Harst, P, Stefansson, K, Munroe, PB, Arking, DE, Lo, CW, and Jamshidi, Y
Published: 2018

22. Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries

Author: Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, XQ, Franceschini, N, Cheng, CY (Ching-Yu), Sim, XL, Vojinovic, Dina, Marten, J, Musani, SK, Li, CW, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, S M, Wojczynski, MK, Alver, M, Boissel, M, Cai, QY, Campbell, A (Archie), Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, MI, Hsu, FC, Jackson, AU, Kahonen, M, Kasturiratne, A, Komulainen, P, Kuhnel, B, Laguzzi, F, Luan, J, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stancakova, A, Takeuchi, F, Tayo, BO, van der Most, PJ, Varga, TV, Vitart, V, Wang, YJ, Ware, EB, Warren, HR, Weiss, S, Wen, WQ, Yanek, LR, Zhang, WH, Zhao, JH, Afaq, S, Amin, Najaf, Amini, M, Arking, DE, Aung, T, Boerwinkle, E, Borecki, I, Broeckel, U, Brown, M, Brumat, M, Burke, GL, Canouil, M, Chakravarti, A, Charumathi, S, Chen, YDI, Connell, JM, Correa, A, Fuentes, LDL, de Mutsert, R, de Silva, HJ, Deng, X, Ding, J, Duan, Q, Eaton, CB, Ehret, G, Eppinga, RN, Evangelou, E, Fau, JD, Felix, SB, Forouhi, NG, Forrester, T, Franco Duran, OH, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, Mohsen, Gigante, B, Gu, CC, Gu, DF, Hagenaars, SP, Hallmans, G, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hirata, M, Howard, BV, Ikram, Arfan, John, U, Katsuya, T, Khor, CC, Kilpelainen, TO, Koh, WP, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lewis, CE, Li, YZ, Lin, S, Liu, JJ, Liu, JM, Loh, M, Louie, T, Magi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Momozawa, Y, Nalls, MA, Nelson, CP, Sotoodehnia, N, Norris, JM, O'Connell, JR, Palmer, ND, Perls, T, Pedersen, NL, Peters, A, Peyser, PA, Poulter, N, Raffel, LJ, Raitakari, OT, Roll, K, Rose, LM, Rosendaal, FR, Rotter, JI, Schmidt, CO, Schreiner, PJ, Schupf, N, Scott, WR, Sever, PS, Shi, Y, Sidney, S, Sims, M, Sitlani, CM, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Stringham, HM, Tan, NYQ, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Turner, ST, Uitterlinden, André, Vollenweider, P, Waldenberger, M, Wang, LH, Wang, YX, Wei, W, Williams, C, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JB, Kamatani, Y, Kato, N, Kooner, JS, Kutalik, Z, Laakso, M, Laurie, CC, Leander, K, Lehtimaki, T, Study, LC, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Poiasek, O, Porteous, DJ, Rauramaa, R, Samani, NJ, Scott, J, Shu, XO, van der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Wu, TC, Zheng, W, Bouchard, C, Christensen, K, Evans, MK, Gudnason, V, Horta, BL, Kardia, SLR, Liu, YM, Pereira, AC, Psaty, BM, Ridker, PM, van Dam, RM, Gauderman, WJ, Zhu, XF, Mook, Dennis, Fornage, M, Rotimi, CN, Cupples, LA, Kelly, TN, Fox, ER, Hayward, C, Duijn, Cornelia, Tai, ES, Wong, TY, Kooperberg, C, Palmas, W, Rice, K, Morrison, AC, Elliott, P, Caulfield, MJ, Munroe, PB, Rao, DC, Province, MA, Levy, D, Feitosa, MF, Kraja, AT, Chasman, DI, Sung, YJ, Winkler, TW, Ntalla, I, Guo, XQ, Franceschini, N, Cheng, CY (Ching-Yu), Sim, XL, Vojinovic, Dina, Marten, J, Musani, SK, Li, CW, Bentley, AR, Brown, MR, Schwander, K, Richard, MA, Noordam, R, Aschard, H, Bartz, TM, Bielak, LF, Dorajoo, R, Fisher, V, Hartwig, FP, Horimoto, A, Lohman, KK, Manning, AK, Rankinen, T, Smith, AV, Tajuddin, S M, Wojczynski, MK, Alver, M, Boissel, M, Cai, QY, Campbell, A (Archie), Chai, JF, Chen, X, Divers, J, Gao, C, Goel, A, Hagemeijer, Y, Harris, SE, He, MI, Hsu, FC, Jackson, AU, Kahonen, M, Kasturiratne, A, Komulainen, P, Kuhnel, B, Laguzzi, F, Luan, J, Matoba, N, Nolte, IM, Padmanabhan, S, Riaz, M, Rueedi, R, Robino, A, Said, MA, Scott, RA, Sofer, T, Stancakova, A, Takeuchi, F, Tayo, BO, van der Most, PJ, Varga, TV, Vitart, V, Wang, YJ, Ware, EB, Warren, HR, Weiss, S, Wen, WQ, Yanek, LR, Zhang, WH, Zhao, JH, Afaq, S, Amin, Najaf, Amini, M, Arking, DE, Aung, T, Boerwinkle, E, Borecki, I, Broeckel, U, Brown, M, Brumat, M, Burke, GL, Canouil, M, Chakravarti, A, Charumathi, S, Chen, YDI, Connell, JM, Correa, A, Fuentes, LDL, de Mutsert, R, de Silva, HJ, Deng, X, Ding, J, Duan, Q, Eaton, CB, Ehret, G, Eppinga, RN, Evangelou, E, Fau, JD, Felix, SB, Forouhi, NG, Forrester, T, Franco Duran, OH, Friedlander, Y, Gandin, I, Gao, H, Ghanbari, Mohsen, Gigante, B, Gu, CC, Gu, DF, Hagenaars, SP, Hallmans, G, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hirata, M, Howard, BV, Ikram, Arfan, John, U, Katsuya, T, Khor, CC, Kilpelainen, TO, Koh, WP, Krieger, JE, Kritchevsky, SB, Kubo, M, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lehne, B, Lewis, CE, Li, YZ, Lin, S, Liu, JJ, Liu, JM, Loh, M, Louie, T, Magi, R, McKenzie, CA, Meitinger, T, Metspalu, A, Milaneschi, Y, Milani, L, Mohlke, KL, Momozawa, Y, Nalls, MA, Nelson, CP, Sotoodehnia, N, Norris, JM, O'Connell, JR, Palmer, ND, Perls, T, Pedersen, NL, Peters, A, Peyser, PA, Poulter, N, Raffel, LJ, Raitakari, OT, Roll, K, Rose, LM, Rosendaal, FR, Rotter, JI, Schmidt, CO, Schreiner, PJ, Schupf, N, Scott, WR, Sever, PS, Shi, Y, Sidney, S, Sims, M, Sitlani, CM, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Stringham, HM, Tan, NYQ, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Turner, ST, Uitterlinden, André, Vollenweider, P, Waldenberger, M, Wang, LH, Wang, YX, Wei, W, Williams, C, Yao, J, Yu, CZ, Yuan, JM, Zhao, W, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Deary, IJ, Esko, T, Farrall, M, Franks, PW, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Jonas, JB, Kamatani, Y, Kato, N, Kooner, JS, Kutalik, Z, Laakso, M, Laurie, CC, Leander, K, Lehtimaki, T, Study, LC, Magnusson, PKE, Oldehinkel, AJ, Penninx, B, Poiasek, O, Porteous, DJ, Rauramaa, R, Samani, NJ, Scott, J, Shu, XO, van der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Weir, DR, Wickremasinghe, AR, Wu, TC, Zheng, W, Bouchard, C, Christensen, K, Evans, MK, Gudnason, V, Horta, BL, Kardia, SLR, Liu, YM, Pereira, AC, Psaty, BM, Ridker, PM, van Dam, RM, Gauderman, WJ, Zhu, XF, Mook, Dennis, Fornage, M, Rotimi, CN, Cupples, LA, Kelly, TN, Fox, ER, Hayward, C, Duijn, Cornelia, Tai, ES, Wong, TY, Kooperberg, C, Palmas, W, Rice, K, Morrison, AC, Elliott, P, Caulfield, MJ, Munroe, PB, Rao, DC, Province, MA, and Levy, D
Published: 2018

23. ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals

Author: Bihlmeyer, NA, Brody, JA, Smith, AV, Warren, HR, Lin, HH, Isaacs, Aaron, Liu, CT, Marten, J, Radmanesh, F, Hall, LM, Grarup, N, Mei, H, Muller-Nurasyid, M, Huffman, JE, Verweij, N, Guo, XQ, Yao, J, Li-Gao, RF, van den Berg, Marten, Weiss, S, Prins, BP, van Setten, J, Haessler, J, Lyytikainen, LP, Li, M, Alonso, A, Soliman, EZ, Bis, JC, Austin, T, Chen, YDI, Psaty, BM, Harrris, TB, Launer, LJ, Padmanabhan, S, Dominiczak, A, Huang, PL, Xie, ZJ, Ellinor, PT, Kors, Jan, Campbell, A (Archie), Murray, AD, Nelson, CP, Tobin, MD, Bork-Jensen, J, Hansen, T, Pedersen, O, Linneberg, A, Sinner, MF, Peters, A, Waldenberger, M, Meitinger, T, Perz, S, Kolcic, I, Rudan, I, de Boer, RA, Meer, P, Lin, H J, Taylor, KD, de Mutsert, R, Trompet, S, Jukema, JW, Maan, AC, Stricker, Bruno, Rivadeneira, Fernando, Uitterlinden, André, Volker, U, Homuth, G, Volzke, H, Felix, SB, Mangino, M, Spector, TD, Bots, ML, Perez, M, Raitakari, OT, Kahonen, M, Mononen, N, Gudnason, V, Munroe, PB, Lubitz, SA, Duijn, Cornelia, Newton-Cheh, CH, Hayward, C, Rosand, J, Samani, NJ, Kanters, JK, Wilson, JG, Kaab, S, Polasek, O, van der Harst, P, Heckbert, SR, Rotter, JI, Mook, Dennis, Eij-Gelsheim, M, Dorr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimaki, T, Arking, DE, Sotoodehnia, N, Bihlmeyer, NA, Brody, JA, Smith, AV, Warren, HR, Lin, HH, Isaacs, Aaron, Liu, CT, Marten, J, Radmanesh, F, Hall, LM, Grarup, N, Mei, H, Muller-Nurasyid, M, Huffman, JE, Verweij, N, Guo, XQ, Yao, J, Li-Gao, RF, van den Berg, Marten, Weiss, S, Prins, BP, van Setten, J, Haessler, J, Lyytikainen, LP, Li, M, Alonso, A, Soliman, EZ, Bis, JC, Austin, T, Chen, YDI, Psaty, BM, Harrris, TB, Launer, LJ, Padmanabhan, S, Dominiczak, A, Huang, PL, Xie, ZJ, Ellinor, PT, Kors, Jan, Campbell, A (Archie), Murray, AD, Nelson, CP, Tobin, MD, Bork-Jensen, J, Hansen, T, Pedersen, O, Linneberg, A, Sinner, MF, Peters, A, Waldenberger, M, Meitinger, T, Perz, S, Kolcic, I, Rudan, I, de Boer, RA, Meer, P, Lin, H J, Taylor, KD, de Mutsert, R, Trompet, S, Jukema, JW, Maan, AC, Stricker, Bruno, Rivadeneira, Fernando, Uitterlinden, André, Volker, U, Homuth, G, Volzke, H, Felix, SB, Mangino, M, Spector, TD, Bots, ML, Perez, M, Raitakari, OT, Kahonen, M, Mononen, N, Gudnason, V, Munroe, PB, Lubitz, SA, Duijn, Cornelia, Newton-Cheh, CH, Hayward, C, Rosand, J, Samani, NJ, Kanters, JK, Wilson, JG, Kaab, S, Polasek, O, van der Harst, P, Heckbert, SR, Rotter, JI, Mook, Dennis, Eij-Gelsheim, M, Dorr, M, Jamshidi, Y, Asselbergs, FW, Kooperberg, C, Lehtimaki, T, Arking, DE, and Sotoodehnia, N
Published: 2018

24. Large-scale gene-centric analysis identifies novel variants for coronary artery disease

Author: Butterworth, As, Braund, Ps, Farrall, M, Hardwick, Rj, Saleheen, D, Peden, Jf, Soranzo, N, Chambers, Jc, Sivapalaratnam, S, Kleber, Me, Keating, B, Qasim, A, Klopp, N, Erdmann, J, Assimes, Tl, Ball, Sg, Balmforth, Aj, Barnes, Ta, Basart, H, Baumert, J, Bezzina, Cr, Boerwinkle, E, Boehm, Bo, Brocheton, J, Bugert, P, Cambien, F, Clarke, R, Codd, V, Collins, R, Couper, D, Cupples, La, de Jong JS, Diemert, P, Ejebe, K, Elbers, Cc, Elliott, P, Fornage, M, Franzosi, Mg, Frossard, P, Garner, S, Goel, A, Goodall, Ah, Hengstenberg, C, Hunt, Se, Kastelein, Jj, Klungel, Oh, Klüter, H, Koch, K, König, Ir, Kooner, As, Laaksonen, R, Lathrop, M, Li, M, Liu, K, Mcpherson, R, Musameh, Md, Musani, S, Nelson, Cp, O'Donnell, Cj, Ongen, H, Papanicolaou, G, Peters, A, Peters, Bj, Potter, S, Psaty, Bm, Qu, L, Rader, Dj, Rasheed, A, Rice, C, Scott, J, Seedorf, U, Sehmi, Js, Sotoodehnia, N, Stark, K, Stephens, J, van der Schoot CE, van der Schouw YT, Thorsteinsdottir, U, Tomaszewski, M, van der Harst, P, Vasan, Rs, Wilde, Aa, Willenborg, C, Winkelmann, Br, Zaidi, M, Zhang, W, Ziegler, A, de Bakker PI, Koenig, W, Mätz, W, Trip, Md, Reilly, Mp, Kathiresan, S, Schunkert, H, Hamsten, A, Hall, As, Kooner, Js, Thompson, Sg, Thompson, Jr, Deloukas, P, Ouwehand, Wh, Watkins, H, Danesh, J, Samani, Nj, Barnes, T, Rafelt, S, Bruinsma, N, Dekker, Lr, Henriques, Jp, Koch, Kt, de Winter RJ, Alings, M, Allaart, Cf, Gorgels, Ap, Verheugt, Fw, Mueller, M, Meisinger, C, Derohannessian, S, Mehta, Nn, Ferguson, J, Hakonarson, H, Matthai, W, Wilensky, R, Hopewell, Jc, Parish, S, Linksted, P, Notman, J, Gonzalez, H, Young, A, Ostley, T, Munday, A, Goodwin, N, Verdon, V, Shah, S, Cobb, L, Edwards, C, Mathews, C, Gunter, R, Benham, J, Davies, C, Cobb, M, Crowther, J, Richards, A, Silver, M, Tochlin, S, Mozley, S, Clark, S, Radley, M, Kourellias, K, Silveira, A, Söderholm, B, Olsson, P, Barlera, S, Tognoni, G, Rust, S, Assmann, G, Heath, S, Zelenika, D, Gut, I, Green, F, Peden, J, Aly, A, Anner, K, Björklund, K, Blomgren, G, Cederschiöld, B, Danell Toverud, K, Eriksson, P, Grundstedt, U, Heinonen, M, Hellénius, Ml, van't Hooft, F, Husman, K, Lagercrantz, J, Larsson, A, Larsson, M, Mossfeldt, M, Mälarstig, A, Olsson, G, Sabater Lleal, M, Sennblad, B, Strawbridge, R, Öhrvik, J, Zaman, Ks, Mallick, Nh, Azhar, M, Samad, A, Ishaq, M, Shah, N, Samuel, M, Reilly, M, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, S, Andersen, K, Anderson, Jl, Ardissino, D, Becker, Lc, Becker, Dm, Berger, K, Bis, Jc, Boekholdt, Sm, Brown, Mj, Burnett, Ms, Buysschaert, I, Carlquist, Jf, Chen, L, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, J, Do, R, Doering, A, El Mokhtari NE, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, S, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, D, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Tennstedt, S, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Lambrechts, D, Leander, K, Lieb, W, Lettre, G, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Musunuru, K, Nahrstaedt, J, Nöthen, Mm, Olivieri, Oliviero, Peyvandi, F, Patel, Rs, Patterson, Cc, Quyyumi, Aa, Rallidis, Ls, Roosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Smith, Av, Smith, Tb, Snoep, Jd, Spertus, Ja, Stefansson, K, Stirrups, K, Stoll, M, Tang, Wh, Thorgeirsson, G, Thorleifsson, G, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Awells, G, Wichmann, He, Witteman, Jc, Wright, Bj, Ye, S, Quertermous, T, März, W, Blankenberg, S, Roberts, R, Onland Moret NC, van Setten, J, Verschuren, Wm, Boer, Jm, Wijmenga, C, Hofker, Mh, Maitland van der Zee AH, de Boer, A, Grobbee, De, Attwood, T, Belz, S, Braund, P, Cooper, J, Crisp Hihn, A, Foad, N, Gracey, J, Gray, E, Gwilliams, R, Heimerl, S, Jolley, J, Krishnan, U, Lloyd Jones, H, Lugauer, I, Lundmark, P, Moore, Js, Muir, D, Murray, E, Neudert, J, Niblett, D, O'Leary, K, Pollard, H, Rankin, A, Rice, Cm, Sager, H, Sambrook, J, Schmitz, G, Scholz, M, Schroeder, L, Syvannen, Ac, Wallace, C., Cardiologie, RS: CAPHRI School for Public Health and Primary Care, Vascular Medicine, Other departments, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Landsteiner Laboratory, Clinical Haematology, Pulmonology, and Medical Research Council (MRC)
Subjects: Male, Cancer Research, Candidate gene, Epidemiology, Genome-wide association study, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiovascular, 0302 clinical medicine, GENETICS & HEREDITY, Genetics (clinical), Genetics, 0303 health sciences, Cardiovascular diseases [NCEBP 14], Middle Aged, 3. Good health, CYP17A1, Genetic Epidemiology, Genome-wide association, Myocardial-infarction, Susceptibility loci, Risk, Atherosclerosis, Metanalysis, Lipoprotein, Medicine, Female, Life Sciences & Biomedicine, Research Article, Asian Continental Ancestry Group, Adult, SUSCEPTIBILITY LOCI, lcsh:QH426-470, European Continental Ancestry Group, Biology, Polymorphism, Single Nucleotide, coronary artery disease, genetics, White People, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Asian People, Genetic variation, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Molecular Biology, Gene, METAANALYSIS, Ecology, Evolution, Behavior and Systematics, Genetic Association Studies, Cardiovascular Disease Epidemiology, Alleles, 030304 developmental biology, Aged, 0604 Genetics, Science & Technology, Case-control study, Genetic Variation, Human Genetics, Odds ratio, large-scale gene analysis, lcsh:Genetics, LIPOPROTEIN, MYOCARDIAL-INFARCTION, ATHEROSCLEROSIS, Case-Control Studies, Genetics of Disease, IBC 50K CAD Consortium, Developmental Biology, Genome-Wide Association Study
Abstract: Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through which the novel variants could affect CAD risk were explored through association tests with vascular risk factors and gene expression. We confirmed associations of several previously known CAD susceptibility loci (eg, 9p21.3:p, Author Summary Coronary artery disease (CAD) has a strong genetic basis that remains poorly characterised. Using a custom-designed array, we tested the association with CAD of almost 50,000 common and low frequency variants in ∼2,000 genes of known or suspected cardiovascular relevance. We genotyped the array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin) and attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. We report the novel association of variants in or near four genes with CAD and in additional studies identify potential mechanisms by which some of these novel variants affect CAD risk. Interestingly, we found that these variants, as well as the majority of previously reported CAD variants, have similar associations in Europeans and South Asians. Contrary to prior expectations, many previously suggested candidate genes did not show evidence of any effect on CAD risk, and neither did we identify any novel low frequency alleles with strong effects amongst the genes tested. Discovery of novel genes associated with heart disease may help to further understand the aetiology of cardiovascular disease and identify new targets for therapeutic interventions.
Published: 2016

25. Discovery of novel heart rate-associated loci using the Exome Chip

Author: van den Berg, Marten, Warren, HR, Cabrera, C P, Verweij, N, Mifsud, B, Haessler, J, Bihlmeyer, NA, Fu, Y P, Weiss, S, Lin, H J, Grarup, N, Li-Gao, RF, Pistis, G, Shah, N, Brody, JA, Muller-Nurasyid, M, Lin, HH, Mei, H, Smith, AV, Lyytikainen, LP, Hall, LM, van Setten, J, Trompet, S, Prins, BP, Isaacs, Aaron, Radmanesh, F, Marten, J, Entwistle, A, Kors, Jan, Silva Aldana, Claudia, Alonso, A, Bis, JC, de Boer, R, de Haan, HG, de Mutsert, R, Dedoussis, G, Dominiczak, AF, Doney, ASF, Ellinor, PT, Eppinga, RN, Felix, SB, Guo, XQ, Hagemeijer, Y, Hansen, T, Harris, TB, Heckbert, SR, Huang, PL, Hwang, SJ, Kahonen, M, Kanters, JK, Kolcic, I, Launer, LJ, Li, M, Yao, J, Linneberg, A, Liu, SM, Macfarlane, PW, Mangino, M, Morris, AD, Mulas, A, Murray, AD, Nelson, CP, Orru, M, Padmanabhan, S, Peters, A, Porteous, DJ, Poulter, N, Psaty, BM, Qi, LH, Raitakari, OT, Rivadeneira, Fernando, Roselli, C, Rudan, I, Sattar, N, Sever, P, Sinner, MF, Soliman, EZ, Spector, TD, Stanton, AV, Stirrups, K E, Taylor, KD, Tobin, MD, Uitterlinden, André, Vaartjes, I, Hoes, AW, van der Meer, P, Volker, U, Waldenberger, M, Xie, ZJ, Zoledziewska, M, Tinker, A, Polasek, O, Rosand, J, Jamshidi, Y, Duijn, Cornelia, Zeggini, E, Jukema, JW, Asselbergs, FW, Samani, NJ, Lehtimaki, T, Gudnason, V, Wilson, J, Lubitz, SA, Kaab, S, Sotoodehnia, N, Caulfield, MJ, Palmer, CNA, Sanna, S, Mook-Kanamori, DO, Deloukas, P, Pedersen, O, Rotter, JI, Dorr, M, O'Donnell, CJ, Hayward, C, Arking, DE, Kooperberg, C, van der Harst, P, Eijgelsheim, Mark, Stricker, Bruno, Munroe, PB, van den Berg, Marten, Warren, HR, Cabrera, C P, Verweij, N, Mifsud, B, Haessler, J, Bihlmeyer, NA, Fu, Y P, Weiss, S, Lin, H J, Grarup, N, Li-Gao, RF, Pistis, G, Shah, N, Brody, JA, Muller-Nurasyid, M, Lin, HH, Mei, H, Smith, AV, Lyytikainen, LP, Hall, LM, van Setten, J, Trompet, S, Prins, BP, Isaacs, Aaron, Radmanesh, F, Marten, J, Entwistle, A, Kors, Jan, Silva Aldana, Claudia, Alonso, A, Bis, JC, de Boer, R, de Haan, HG, de Mutsert, R, Dedoussis, G, Dominiczak, AF, Doney, ASF, Ellinor, PT, Eppinga, RN, Felix, SB, Guo, XQ, Hagemeijer, Y, Hansen, T, Harris, TB, Heckbert, SR, Huang, PL, Hwang, SJ, Kahonen, M, Kanters, JK, Kolcic, I, Launer, LJ, Li, M, Yao, J, Linneberg, A, Liu, SM, Macfarlane, PW, Mangino, M, Morris, AD, Mulas, A, Murray, AD, Nelson, CP, Orru, M, Padmanabhan, S, Peters, A, Porteous, DJ, Poulter, N, Psaty, BM, Qi, LH, Raitakari, OT, Rivadeneira, Fernando, Roselli, C, Rudan, I, Sattar, N, Sever, P, Sinner, MF, Soliman, EZ, Spector, TD, Stanton, AV, Stirrups, K E, Taylor, KD, Tobin, MD, Uitterlinden, André, Vaartjes, I, Hoes, AW, van der Meer, P, Volker, U, Waldenberger, M, Xie, ZJ, Zoledziewska, M, Tinker, A, Polasek, O, Rosand, J, Jamshidi, Y, Duijn, Cornelia, Zeggini, E, Jukema, JW, Asselbergs, FW, Samani, NJ, Lehtimaki, T, Gudnason, V, Wilson, J, Lubitz, SA, Kaab, S, Sotoodehnia, N, Caulfield, MJ, Palmer, CNA, Sanna, S, Mook-Kanamori, DO, Deloukas, P, Pedersen, O, Rotter, JI, Dorr, M, O'Donnell, CJ, Hayward, C, Arking, DE, Kooperberg, C, van der Harst, P, Eijgelsheim, Mark, Stricker, Bruno, and Munroe, PB
Published: 2017

26. Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Author: Okada, Y, Sim, X, Go, Mj, Wu, Jy, Gu, D, Takeuchi, F, Takahashi, A, Maeda, S, Tsunoda, T, Chen, P, Lim, Sc, Wong, Ty, Liu, J, Young, Tl, Aung, T, Seielstad, M, Teo, Yy, Kim, Yj, Lee, Jy, Han, Bg, Kang, D, Chen, Ch, Tsai, Fj, Chang, Lc, Fann, Sj, Mei, H, Rao, Dc, Hixson, Je, Chen, S, Katsuya, T, Isono, M, Ogihara, T, Chambers, Jc, Zhang, W, Kooner, Js, Kidneygen, Consortium, Ckdgen, Consortium, Albrecht, E, Gugc, Consortium, Yamamoto, K, Kubo, M, Nakamura, Y, Kamatani, N, Kato, N, He, J, Chen, Yt, Cho, Ys, Tai, Es, Tanaka, T., Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, Js, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Smith, Gd, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Ferrucci, L, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, van der Heide JJ, Hepkema, Bg, Hernandez Fuentes, M, Hypponen, E, Johnson, T, de Jong PE, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Melander, O, Munroe, Pb, Nordfors, L, Parsa, A, Peltonen, L, Penninx, Bw, Perucha, E, Pouta, A, Prokopenko, I, Roderick, Pj, Ruokonen, A, Samani, Nj, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Shuldiner, Ar, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Tanaka, T, Ubink Veltmaat LJ, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Mooser, V, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliott, P, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Glazer, Nl, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Li, M, Schmidt, H, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, Ad, Dehghan, A, Teumer, A, Paré, G, Atkinson, Ej, Zeller, T, Lohman, K, Cornelis, Mc, Probst Hensch NM, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Boerwinkle, E, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer IH, Haritunians, T, Lumley, T, Siscovick, D, Psaty, Bm, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schillert, A, Ziegler, A, Wild, Ps, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, Ts, Illig, T, Klopp, N, Meisinger, C, Wichmann, He, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, Å, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Schreiber, S, Aulchenko, Ys, Felix, Jf, Rivadeneira, F, Uitterlinden, Ag, Hofman, A, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Blankenberg, S, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Wang, W, Gudnason, V, Coresh, J, Schmidt, R, Shlipak, Mg, van Duijn CM, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Witteman, Jc, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, Cs, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, M, Haller, T, Kutalik, Z, Shi, J, Middelberg, Ps, Gaffo, Al, Pirastu, N, Li, G, Huffman, J, Yengo, L, Zhao, Jh, Demirkan, A, Feitosa, Mf, Liu, X, Malerba, Giovanni, Lopez, Lm, Li, X, Kleber, Me, Hicks, Aa, Nolte, Im, Johansson, A, Murgia, F, Peden, Jf, Steri, M, Tenesa, A, Salo, P, Mangino, M, Rose, Lm, Lehtimäki, T, Woodward, Om, Tin, A, Müller, C, Oldmeadow, C, Putku, M, Czamara, D, Kraft, P, Frogheri, L, Thun, Ga, Grotevendt, A, Gislason, Gk, Mcardle, P, Schallert, M, Martin, Ng, Montgomery, Gw, Jacobs DR Jr, Liu, K, D'Adamo, P, Ulivi, S, Rotter, Ji, Navaro, P, Balkau, B, Froguel, P, Esko, T, Salumets, A, Khaw, Kt, Langenberg, C, Kraja, A, Zhang, Q, Scott, Rj, Holliday, Eg, Org, E, Viigimaa, M, Bandinelli, S, Metter, Je, Lupo, Antonio, Trabetti, Elisabetta, Sorice, R, Döring, A, Lattka, E, Strauch, K, Theis, F, Waldenberger, M, Davies, G, Gow, Aj, Bruinenberg, M, Stolk, Rp, Winkelmann, Br, Boehm, Bo, Lucae, S, Curhan, G, Mudgal, P, Plenge, Rm, Portas, L, Persico, I, Kirin, M, Mateo Leach, I, van Gilst WH, Goel, A, Ongen, H, von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, Mg, Schurmann, C, Budde, K, Ernst, F, Farrington, Sm, Theodoratou, E, Jula, A, Perola, M, Salomaa, V, Shin, Sy, Sala, C, Kähönen, M, Viikari, J, Hengstenberg, C, Nelson, Cp, Meschia, Jf, Nalls, Ma, Sharma, P, Singleton, Ab, Burnier, M, Attia, J, Laan, M, Hillege, Hl, Kloiber, S, Choi, H, Pirastu, M, Tore, S, Whitfield, Jb, Fornage, M, Gasparini, P, Siscovick, Ds, Bouatia Naji, N, Metspalu, A, Borecki, Ib, Gambaro, G, Deary, Ij, Wolffenbuttel, Bh, März, W, Watkins, H, Schipf, S, Dunlop, Mg, Ripatti, S, Toniolo, D, Raitakari, O, Ciullo, M, Caulfield, M, Gieger, C., Okada, Y, Sim, X, Go, Mj, Wu, Jy, Gu, D, Takeuchi, F, Takahashi, A, Maeda, S, Tsunoda, T, Chen, P, Lim, Sc, Wong, Ty, Liu, J, Young, Tl, Aung, T, Seielstad, M, Teo, Yy, Kim, Yj, Lee, Jy, Han, Bg, Kang, D, Chen, Ch, Tsai, Fj, Chang, Lc, Fann, Sj, Mei, H, Rao, Dc, Hixson, Je, Chen, S, Katsuya, T, Isono, M, Ogihara, T, Chambers, Jc, Zhang, W, Kooner, J, Albrecht, E, Yamamoto, K, Kubo, M, Nakamura, Y, Kamatani, N, Kato, N, He, J, Chen, Yt, Cho, Y, Tai, E, Tanaka, T, Lord, Gm, van der Harst, P, Lawlor, Da, Sehmi, J, Gale, Dp, Wass, Mn, Ahmadi, Kr, Bakker, Sj, Beckmann, J, Bilo, Hj, Bochud, M, Brown, Mj, Caulfield, Mj, Connell, Jm, Cook, Ht, Cotlarciuc, I, Smith, Gd, de Silva, R, Deng, G, Devuyst, O, Dikkeschei, Ld, Dimkovic, N, Dockrell, M, Dominiczak, A, Ebrahim, S, Eggermann, T, Farrall, M, Ferrucci, L, Floege, J, Forouhi, Ng, Gansevoort, Rt, Han, X, Hedblad, B, van der Heide, Jj, Hepkema, Bg, Hernandez Fuentes, M, Hypponen, E, Johnson, T, de Jong, Pe, Kleefstra, N, Lagou, V, Lapsley, M, Li, Y, Loos, Rj, Luan, J, Luttropp, K, Maréchal, C, Melander, O, Munroe, Pb, Nordfors, L, Parsa, A, Peltonen, L, Penninx, Bw, Perucha, E, Pouta, A, Prokopenko, I, Roderick, Pj, Ruokonen, A, Samani, Nj, Sanna, S, Schalling, M, Schlessinger, D, Schlieper, G, Seelen, Ma, Shuldiner, Ar, Sjögren, M, Smit, Jh, Snieder, H, Soranzo, N, Spector, Td, Stenvinkel, P, Sternberg, Mj, Swaminathan, R, Ubink Veltmaat, Lj, Uda, M, Vollenweider, P, Wallace, C, Waterworth, D, Zerres, K, Waeber, G, Wareham, Nj, Maxwell, Ph, Mccarthy, Mi, Jarvelin, Mr, Mooser, V, Abecasis, Gr, Lightstone, L, Scott, J, Navis, G, Elliott, P, Köttgen, A, Pattaro, C, Böger, Ca, Fuchsberger, C, Olden, M, Glazer, Nl, Gao, X, Yang, Q, Smith, Av, O'Connell, Jr, Li, M, Schmidt, H, Isaacs, A, Ketkar, S, Hwang, Sj, Johnson, Ad, Dehghan, A, Teumer, A, Paré, G, Atkinson, Ej, Zeller, T, Lohman, K, Cornelis, Mc, Probst Hensch, Nm, Kronenberg, F, Tönjes, A, Hayward, C, Aspelund, T, Eiriksdottir, G, Launer, Lj, Harris, Tb, Rampersaud, E, Mitchell, Bd, Arking, De, Boerwinkle, E, Struchalin, M, Cavalieri, M, Singleton, A, Giallauria, F, Metter, J, de Boer, Ih, Haritunians, T, Lumley, T, Siscovick, D, Psaty, Bm, Zillikens, Mc, Oostra, Ba, Feitosa, M, Province, M, de Andrade, M, Turner, St, Schillert, A, Ziegler, A, Wild, P, Schnabel, Rb, Wilde, S, Munzel, Tf, Leak, T, Illig, T, Klopp, N, Meisinger, C, Wichmann, He, Koenig, W, Zgaga, L, Zemunik, T, Kolcic, I, Minelli, C, Hu, Fb, Johansson, Å, Igl, W, Zaboli, G, Wild, Sh, Wright, Af, Campbell, H, Ellinghaus, D, Schreiber, S, Aulchenko, Y, Felix, Jf, Rivadeneira, F, Uitterlinden, Ag, Hofman, A, Imboden, M, Nitsch, D, Brandstätter, A, Kollerits, B, Kedenko, L, Mägi, R, Stumvoll, M, Kovacs, P, Boban, M, Campbell, S, Endlich, K, Völzke, H, Kroemer, Hk, Nauck, M, Völker, U, Polasek, O, Vitart, V, Badola, S, Parker, An, Ridker, Pm, Kardia, Sl, Blankenberg, S, Liu, Y, Curhan, Gc, Franke, A, Rochat, T, Paulweber, B, Wang, W, Gudnason, V, Coresh, J, Schmidt, R, Shlipak, Mg, van Duijn, Cm, Borecki, I, Krämer, Bk, Rudan, I, Gyllensten, U, Wilson, Jf, Witteman, Jc, Pramstaller, Pp, Rettig, R, Hastie, N, Chasman, Di, Kao, Wh, Heid, Im, Fox, C, Krumsiek, J, Hundertmark, C, Pistis, G, Ruggiero, D, O'Seaghdha, M, Haller, T, Kutalik, Z, Shi, J, Middelberg, P, Gaffo, Al, Pirastu, Nicola, Li, G, Huffman, J, Yengo, L, Zhao, Jh, Demirkan, A, Feitosa, Mf, Liu, X, Malerba, G, Lopez, Lm, Li, X, Kleber, Me, Hicks, Aa, Nolte, Im, Johansson, A, Murgia, F, Peden, Jf, Steri, M, Tenesa, A, Salo, P, Mangino, M, Rose, Lm, Lehtimäki, T, Woodward, Om, Tin, A, Müller, C, Oldmeadow, C, Putku, M, Czamara, D, Kraft, P, Frogheri, L, Thun, Ga, Grotevendt, A, Gislason, Gk, Mcardle, P, Schallert, M, Martin, Ng, Montgomery, Gw, Jacobs DR, Jr, Liu, K, D'Adamo, ADAMO PIO, Ulivi, S, Rotter, Ji, Navaro, P, Balkau, B, Froguel, P, Esko, T, Salumets, A, Khaw, Kt, Langenberg, C, Kraja, A, Zhang, Q, Scott, Rj, Holliday, Eg, Org, E, Viigimaa, M, Bandinelli, S, Metter, Je, Lupo, A, Trabetti, E, Sorice, R, Döring, A, Lattka, E, Strauch, K, Theis, F, Waldenberger, M, Davies, G, Gow, Aj, Bruinenberg, M, Stolk, Rp, Winkelmann, Br, Boehm, Bo, Lucae, S, Curhan, G, Mudgal, P, Plenge, Rm, Portas, L, Persico, I, Kirin, M, Mateo Leach, I, van Gilst, Wh, Goel, A, Ongen, H, von Eckardstein, A, Cucca, F, Nagaraja, R, Piras, Mg, Schurmann, C, Budde, K, Ernst, F, Farrington, Sm, Theodoratou, E, Jula, A, Perola, M, Salomaa, V, Shin, Sy, Sala, C, Kähönen, M, Viikari, J, Hengstenberg, C, Nelson, Cp, Meschia, Jf, Nalls, Ma, Sharma, P, Singleton, Ab, Burnier, M, Attia, J, Laan, M, Hillege, Hl, Kloiber, S, Choi, H, Pirastu, M, Tore, S, Whitfield, Jb, Fornage, M, Gasparini, Paolo, Bouatia Naji, N, Metspalu, A, Borecki, Ib, Gambaro, G, Deary, Ij, Wolffenbuttel, Bh, März, W, Watkins, H, Schipf, S, Dunlop, Mg, Ripatti, S, Toniolo, D, Raitakari, O, Ciullo, M, Caulfield, M, Gieger, C., KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Chambers, J.C., Zhang, W., Lord, G.M., van der Harst, P., Lawlor, D.A., Sehmi, J.S., Gale, D.P., Wass, M.N., Ahmadi, K.R., Bakker, S.J., Beckmann, J., Bilo, H.J., Bochud, M., Brown, M.J., Caulfield, M.J., Connell, J.M., Cook, H.T., Cotlarciuc, I., Smith, G.D., de Silva, R., Deng, G., Devuyst, O., Dikkeschei, L.D., Dimkovic, N., Dockrell, M., Dominiczak, A., Ebrahim, S., Eggermann, T., Farrall, M., Ferrucci, L., Floege, J., Forouhi, N.G., Gansevoort, R.T., Han, X., Hedblad, B., van der Heide, J.J., Hepkema, B.G., Hernandez-Fuentes, M., Hypponen, E., Johnson, T., de Jong, P.E., Kleefstra, N., Lagou, V., Lapsley, M., Li, Y., Loos, R.J., Luan, J., Luttropp, K., Maréchal, C., Melander, O., Munroe, P.B., Nordfors, L., Parsa, A., Peltonen, L., Penninx, B.W., Perucha, E., Pouta, A., Prokopenko, I., Roderick, P.J., Ruokonen, A., Samani, N.J., Sanna, S., Schalling, M., Schlessinger, D., Schlieper, G., Seelen, M.A., Shuldiner, A.R., Sjögren, M., Smit, J.H., Snieder, H., Soranzo, N., Spector, T.D., Stenvinkel, P., Sternberg, M.J., Swaminathan, R., Tanaka, T., Ubink-Veltmaat, L.J., Uda, M., Vollenweider, P., Wallace, C., Waterworth, D., Zerres, K., Waeber, G., Wareham, N.J., Maxwell, P.H., McCarthy, M.I., Jarvelin, M.R., Mooser, V., Abecasis, G.R., Lightstone, L., Scott, J., Navis, G., Elliott, P., Kooner, J.S., Köttgen, A., Pattaro, C., Böger, C.A., Fuchsberger, C., Olden, M., Glazer, N.L., Gao, X., Yang, Q., Smith, A.V., O'Connell, J.R., Li, M., Schmidt, H., Isaacs, A., Ketkar, S., Hwang, S.J., Johnson, A.D., Dehghan, A., Teumer, A., Paré, G., Atkinson, E.J., Zeller, T., Lohman, K., Cornelis, M.C., Probst-Hensch, N.M., Kronenberg, F., Tönjes, A., Hayward, C., Aspelund, T., Eiriksdottir, G., Launer, L.J., Harris, T.B., Rampersaud, E., Mitchell, B.D., Arking, D.E., Boerwinkle, E., Struchalin, M., Cavalieri, M., Singleton, A., Giallauria, F., Metter, J., de Boer, I.H., Haritunians, T., Lumley, T., Siscovick, D., Psaty, B.M., Zillikens, M.C., Oostra, B.A., Feitosa, M., Province, M., de Andrade, M., Turner, S.T., Schillert, A., Ziegler, A., Wild, P.S., Schnabel, R.B., Wilde, S., Munzel, T.F., Leak, T.S., Illig, T., Klopp, N., Meisinger, C., Wichmann, H.E., Koenig, W., Zgaga, L., Zemunik, T., Kolcic, I., Minelli, C., Hu, F.B., Johansson, Å., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Schreiber, S., Aulchenko, Y.S., Felix, J.F., Rivadeneira, F., Uitterlinden, A.G., Hofman, A., Imboden, M., Nitsch, D., Brandstätter, A., Kollerits, B., Kedenko, L., Mägi, R., Stumvoll, M., Kovacs, P., Boban, M., Campbell, S., Endlich, K., Völzke, H., Kroemer, H.K., Nauck, M., Völker, U., Polasek, O., Vitart, V., Badola, S., Parker, A.N., Ridker, P.M., Kardia, S.L., Blankenberg, S., Liu, Y., Curhan, G.C., Franke, A., Rochat, T., Paulweber, B., Wang, W., Gudnason, V., Coresh, J., Schmidt, R., Shlipak, M.G., van Duijn, C.M., Borecki, I., Krämer, B.K., Rudan, I., Gyllensten, U., Wilson, J.F., Witteman, J.C., Pramstaller, P.P., Rettig, R., Hastie, N., Chasman, D.I., Kao, W.H., Heid, I.M., Fox, C.S., Albrecht, E., Krumsiek, J., Hundertmark, C., Pistis, G., Ruggiero, D., O'Seaghdha, M., Haller, T., Kutalik, Z., Shi, J., Middelberg, P.S., Gaffo, A.L., Pirastu, N., Li, G., Huffman, J., Yengo, L., Zhao, J.H., Demirkan, A., Feitosa, M.F., Liu, X., Malerba, G., Lopez, L.M., Li, X., Kleber, M.E., Hicks, A.A., Nolte, I.M., Johansson, A., Murgia, F., Peden, J.F., Steri, M., Tenesa, A., Salo, P., Mangino, M., Rose, L.M., Lehtimäki, T., Woodward, O.M., Okada, Y., Tin, A., Müller, C., Oldmeadow, C., Putku, M., Czamara, D., Kraft, P., Frogheri, L., Thun, G.A., Grotevendt, A., Gislason, G.K., McArdle, P., Schallert, M., Martin, N.G., Montgomery, G.W., Kubo, M., Nakamura, Y., Jacobs, D.R., Liu, K., D'Adamo, P., Ulivi, S., Rotter, J.I., Navaro, P., Balkau, B., Froguel, P., Esko, T., Salumets, A., Khaw, K.T., Langenberg, C., Kraja, A., Zhang, Q., Scott, R.J., Holliday, E.G., Org, E., Viigimaa, M., Bandinelli, S., Metter, J.E., Lupo, A., Trabetti, E., Sorice, R., Döring, A., Lattka, E., Strauch, K., Theis, F., Waldenberger, M., Davies, G., Gow, A.J., Bruinenberg, M., Stolk, R.P., Winkelmann, B.R., Boehm, B.O., Lucae, S., Curhan, G., Mudgal, P., Plenge, R.M., Portas, L., Persico, I., Kirin, M., Mateo Leach, I., van Gilst, W.H., Goel, A., Ongen, H., von Eckardstein, A., Cucca, F., Nagaraja, R., Piras, M.G., Schurmann, C., Budde, K., Ernst, F., Farrington, S.M., Theodoratou, E., Jula, A., Perola, M., Salomaa, V., Shin, S.Y., Sala, C., Kähönen, M., Viikari, J., Hengstenberg, C., Nelson, C.P., Meschia, J.F., Nalls, M.A., Sharma, P., Singleton, A.B., Kamatani, N., Burnier, M., Attia, J., Laan, M., Hillege, H.L., Kloiber, S., Choi, H., Pirastu, M., Tore, S., Whitfield, J.B., Fornage, M., Gasparini, P., Siscovick, D.S., Bouatia-Naji, N., Metspalu, A., Borecki, I.B., Gambaro, G., Deary, I.J., Wolffenbuttel, B.H., März, W., Watkins, H., Schipf, S., Dunlop, M.G., Ripatti, S., Toniolo, D., Raitakari, O., Ciullo, M., Caulfield, M., Obstetrics & Gynecology, Medical Informatics, Okada, Yukinori, Sim, Xueling, Go, Min Jin, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L., Aung, Tin, Seielstad, Mark, Teo, Yik-Ying, Kim, Young Jin, Lee, Jong-Young, Han, Bok-Ghee, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Cathy Fann, S. -J. C., Mei, Hao, Rao, Dabeeru C., Hixson, James E., Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Ogihara, Toshio, Chambers, John C., Zhang, Weihua, Kooner, Jaspal S., Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Cho, Yoon Shin, Tai, E-Shyong, Tanaka, Toshihiro, de Silva, R Deng G, Hernandez-Fuentes, M, Ubink-Veltmaat, Lj, Probst-Hensch, Nm, Giallauria, Francesco, Pirastu, N, D'Adamo, P, Gasparini, P, and Bouatia-Naji, N
Subjects: Asian Continental Ancestry Group, kidney, Population, Renal function, Genome-wide association study, Biology, Kidney, Polymorphism, Single Nucleotide, Article, Blood Urea Nitrogen, Cohort Studies, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, Asian People, loci, Asian, medicine, Humans, genetics, Genetic Predisposition to Disease, Renal Insufficiency, Chronic, education, meta-analysis, Genome-Wide Association Study, Genetic association, Genetics, Creatinine, education.field_of_study, ta3121, medicine.disease, Uric Acid, Asian Continental Ancestry Group/genetics, Creatinine/blood, Glomerular Filtration Rate/genetics, Kidney/physiology, Renal Insufficiency, Chronic/genetics, Uric Acid/blood, medicine.anatomical_structure, chemistry, Genetic epidemiology, Cohort Studie, Human, Kidney disease, Glomerular Filtration Rate
Abstract: Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genomewide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 x 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of similar to 110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.
Published: 2012

27. Hypothesis-based analysis of gene-gene interactions and risk of myocardial infarction

Author: Lucas G1, Lluís-Ganella C, Subirana I, Musameh MD, Gonzalez JR, Nelson CP, Sentí M, Myocardial Infarction Genetics Consortium, Wellcome Trust Case Control Consortium, Schwartz SM, Siscovick D, O'Donnell CJ, Melander O, Salomaa V, Purcell S, Altshuler D, Samani NJ, Kathiresan S, Elosua R, Voight BF, Musunuru K, Ardissino D, Mannucci PM, Anand S, Engert JC, Schunkert H, Erdmann J, Reilly MP, Rader DJ, Morgan T, Spertus JA, Stoll M, Girelli D, McKeown PP, Patterson CC, Siscovick DS, Peltonen L, Merlini PA, Berzuini C, Bernardinelli L, Peyvandi F, Tubaro M, Celli P, Ferrario M, Fetiveau R, Marziliano N, Casari G, Galli M, Ribichini F, Rossi M, Bernardi F, Zonzin P, Piazza A, Yee J, Friedlander Y, Marrugat J, Lucas G, Sala J, Ramos R, Meigs JB, Williams G, Nathan DM, MacRae CA, Havulinna AS, Berglund G, Deloukas P, Donnelly P, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Kwiatkowski DP, Mathew CG, McCarthy MI, Ouwehand WH, Parkes M, Pembrey M, Rahman N, Stratton MR, Todd JA, Worthington J, Burton PR, Clayton DG, Cardon LR, Craddock N, Duncanson A, Barrett JC, Davison D, Easton D, Evans D, 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, Ball SG, Balmforth AJ, Barrett JH, Bishop D, Iles MM, Maqbool A, Braund PS, Dixon RJ, Mangino M, Stevens S, Thompson JR, 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, Cardo LR, Cardin NJ, Ferreira T, Pereira-Gale J, Hallgrimsdottir IB, Howie BN, Su Z, Teo YY, Vukcevic D, Lucas, G1, Lluís-Ganella, C, Subirana, I, Musameh, Md, Gonzalez, Jr, Nelson, Cp, Sentí, M, Myocardial Infarction Genetics, Consortium, Wellcome Trust Case Control, Consortium, Schwartz, Sm, Siscovick, D, O'Donnell, Cj, Melander, O, Salomaa, V, Purcell, S, Altshuler, D, Samani, Nj, Kathiresan, S, Elosua, R, Voight, Bf, Musunuru, K, Ardissino, D, Mannucci, Pm, Anand, S, Engert, Jc, Schunkert, H, Erdmann, J, Reilly, Mp, Rader, Dj, Morgan, T, Spertus, Ja, Stoll, M, Girelli, D, Mckeown, Pp, Patterson, Cc, Peltonen, L, Merlini, Pa, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Ferrario, M, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Lucas, G, Sala, J, Ramos, R, Meigs, Jb, Williams, G, Nathan, Dm, Macrae, Ca, Havulinna, A, Berglund, G, Deloukas, P, Donnelly, P, Farrall, M, Gough, Sc, Hall, A, Hattersley, At, Hill, Av, Kwiatkowski, Dp, Mathew, Cg, Mccarthy, Mi, Ouwehand, Wh, Parkes, M, Pembrey, M, Rahman, N, Stratton, Mr, Todd, Ja, Worthington, J, Burton, Pr, Clayton, Dg, Cardon, Lr, Craddock, N, Duncanson, A, Barrett, Jc, Davison, D, Easton, D, Evans, D, 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, Ball, Sg, Balmforth, Aj, Barrett, Jh, Bishop, D, Iles, Mm, Maqbool, A, Braund, P, Dixon, Rj, Mangino, M, Stevens, S, Thompson, Jr, 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, Cardo, Lr, Cardin, Nj, Ferreira, T, Pereira-Gale, J, Hallgrimsdottir, Ib, Howie, Bn, Su, Z, Teo, Yy, and Vukcevic, D
Subjects: Heredity, Epidemiology, Myocardial Infarction, lcsh:Medicine, Genome-wide association study, Coronary Artery Disease, Cardiovascular, Logistic regression, Risk Factors, Cardiac and Cardiovascular Systems, lcsh:Science, Genetics, 0303 health sciences, Multidisciplinary, Medicine (all), 030305 genetics & heredity, Genomics, Genetic Epidemiology, Medicine, Research Article, Human, Risk, Genotype, Genotypes, Reproducibility of Result, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, Genome Analysis Tools, Genome-Wide Association Studies, Humans, Genetic Predisposition to Disease, Risk factor, Allele frequency, Genetic Association Studies, 030304 developmental biology, Genetic association, Biochemistry, Genetics and Molecular Biology (all), Complex Traits, Risk Factor, lcsh:R, Reproducibility of Results, Human Genetics, Epistasis, Genetic, Odds ratio, Genetic epidemiology, Agricultural and Biological Sciences (all), Genetics of Disease, Epistasis, Genetic Polymorphism, Infart de miocardi -- Epidemiologia, lcsh:Q, Population Genetics, Genome-Wide Association Study
Abstract: The genetic loci that have been found by genome-wide association studies to modulate risk of coronary heart disease explain only a fraction of its total variance, and gene-gene interactions have been proposed as a potential source of the remaining heritability. Given the potentially large testing burden, we sought to enrich our search space with real interactions by analyzing variants that may be more likely to interact on the basis of two distinct hypotheses: a biological hypothesis, under which MI risk is modulated by interactions between variants that are known to be relevant for its risk factors; and a statistical hypothesis, under which interacting variants individually show weak marginal association with MI. In a discovery sample of 2,967 cases of early-onset myocardial infarction (MI) and 3,075 controls from the MIGen study, we performed pair-wise SNP interaction testing using a logistic regression framework. Despite having reasonable power to detect interaction effects of plausible magnitudes, we observed no statistically significant evidence of interaction under these hypotheses, and no clear consistency between the top results in our discovery sample and those in a large validation sample of 1,766 cases of coronary heart disease and 2,938 controls from the Wellcome Trust Case-Control Consortium. Our results do not support the existence of strong interaction effects as a common risk factor for MI. Within the scope of the hypotheses we have explored, this study places a modest upper limit on the magnitude that epistatic risk effects are likely to have at the population level (odds ratio for MI risk 1.3–2.0, depending on allele frequency and interaction model).
Published: 2012
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28. blood pressure loci identified with a gene-centricarray

Author: Johnson T, Gaunt TR, Newhouse SJ, Padmanabhan S, Tomaszewski M, Kumari M, Morris RW, Tzoulaki I, O'Brien ET, Poulter NR, Sever P, Shields DC, Thom S, Wannamethee SG, Whincup PH, Brown MJ, Connell JM, Dobson RJ, Howard PJ, Mein CA, Onipinla A, Shaw Hawkins S, Zhang Y, Davey Smith G, Day IN, Lawlor DA, Goodall AH, Cardiogenics Consortium, Fowkes FG, Abecasis GR, Elliott P, Gateva V, Global BPgen Consortium, Braund PS, Burton PR, Nelson CP, Tobin MD, van der Harst P, Glorioso N, Neuvrith H, Salvi E, Staessen JA, Stucchi A, Devos N, Jeunemaitre X, Plouin PF, Tichet J, Juhanson P, Org E, Putku M, Sõber S, Veldre G, Viigimaa M, Levinsson A, Rosengren A, Thelle DS, Hastie CE, Hedner T, Lee WK, Melander O, Wahlstrand B, Hardy R, Wong A, Cooper JA, Palmen J, Chen L, Stewart AF, Wells GA, Westra HJ, Wolfs MG, Clarke R, Franzosi MG, Goel A, Hamsten A, Lathrop M, Peden JF, Seedorf U, Watkins H, Ouwehand WH, Sambrook J, Stephens J, Casas JP, Drenos F, Holmes MV, Kivimaki M, Shah S, Shah T, Talmud PJ, Whittaker J, Wallace C, Delles C, Laan M, Kuh D, Humphries SE, Nyberg F, Cusi D, Roberts R, Newton Cheh C, Franke L, Stanton AV, Dominiczak AF, Farrall M, Hingorani AD, Samani NJ, Caulfield MJ, Munroe P.B., PANICO, SALVATORE, Johnson, T, Gaunt, Tr, Newhouse, Sj, Padmanabhan, S, Tomaszewski, M, Kumari, M, Morris, Rw, Tzoulaki, I, O'Brien, Et, Poulter, Nr, Sever, P, Shields, Dc, Thom, S, Wannamethee, Sg, Whincup, Ph, Brown, Mj, Connell, Jm, Dobson, Rj, Howard, Pj, Mein, Ca, Onipinla, A, Shaw Hawkins, S, Zhang, Y, Davey Smith, G, Day, In, Lawlor, Da, Goodall, Ah, Cardiogenics, Consortium, Fowkes, Fg, Abecasis, Gr, Elliott, P, Gateva, V, Global BPgen, Consortium, Braund, P, Burton, Pr, Nelson, Cp, Tobin, Md, van der Harst, P, Glorioso, N, Neuvrith, H, Salvi, E, Staessen, Ja, Stucchi, A, Devos, N, Jeunemaitre, X, Plouin, Pf, Tichet, J, Juhanson, P, Org, E, Putku, M, Sõber, S, Veldre, G, Viigimaa, M, Levinsson, A, Rosengren, A, Thelle, D, Hastie, Ce, Hedner, T, Lee, Wk, Melander, O, Wahlstrand, B, Hardy, R, Wong, A, Cooper, Ja, Palmen, J, Chen, L, Stewart, Af, Wells, Ga, Westra, Hj, Wolfs, Mg, Clarke, R, Franzosi, Mg, Goel, A, Hamsten, A, Lathrop, M, Peden, Jf, Seedorf, U, Watkins, H, Ouwehand, Wh, Sambrook, J, Stephens, J, Casas, Jp, Drenos, F, Holmes, Mv, Kivimaki, M, Shah, S, Shah, T, Talmud, Pj, Whittaker, J, Wallace, C, Delles, C, Laan, M, Kuh, D, Humphries, Se, Nyberg, F, Cusi, D, Roberts, R, Newton Cheh, C, Franke, L, Stanton, Av, Dominiczak, Af, Farrall, M, Hingorani, Ad, Samani, Nj, Caulfield, Mj, Munroe, P. B., and Panico, Salvatore
Published: 2011

29. Genetically Determined Height and Coronary Artery Disease

Author: Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, N, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, U, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, Kooner,JS, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Landsteiner Laboratory, Clinical Haematology, Other departments, Lee Kong Chian School of Medicine (LKCMedicine), Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Burgess, Stephen [0000-0001-5365-8760], Wareham, Nicholas [0000-0003-1422-2993], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
Subjects: systolic blood pressure, Pathology, BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, genetic association, genotype, cholesterol blood level, insulin blood level, Coronary Artery Disease, 030204 cardiovascular system & hematology, genetic risk, Triglyceride, low density lipoprotein cholesterol, Coronary artery disease, 0302 clinical medicine, high density lipoprotein cholesterol, single nucleotide polymorphism, Risk Factors, genetic variability, Odds Ratio, hyperlipidemia, Science::Medicine [DRNTU], genetics, glucose, risk, 0303 health sciences, medicine.diagnostic_test, non insulin dependent diabetes mellitus, Medicine (all), allele, insulin, triacylglycerol, triacylglycerol, adult, aged, Article, atherosclerosis, bioinformatics, body height, body mass, cardiovascular risk, controlled study, coronary artery disease, development, diastolic blood pressure, female, glucose blood level, human, major clinical study, male, mean arterial pressure, priority journal, pulse pressure, risk factor, smoking, triacylglycerol blood level, blood, complication, risk, Adult, Body Height, Cholesterol, LDL, Genetic Variation, Humans, Hyperlipidemias, Triglycerides, General Medicine, Cholesterol, Cardiology, Adult, medicine.medical_specialty, Inverse Association, Single-nucleotide polymorphism, Endocrinology and Diabetes, LDL, 03 medical and health sciences, Internal medicine, medicine, Risk factor, 030304 developmental biology, Genetic association, business.industry, Odds ratio, medicine.disease, Lipid profile, business, Body mass index
Abstract: BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P
Published: 2015

30. Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Author: Brignell, JL, Perry, MD, Nelson, CP, Willets, JM, Challiss, RAJ, and Davies, NW
Subjects: lcsh:R, lcsh:Medicine, lcsh:Q, lcsh:Science
Abstract: Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone.
Published: 2015

31. 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., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., Fox, C.S., 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., Teumer, A., Gorski, M., Chu, A.Y., Mijatovic, V., Garnaas, M., Tin, A., Sorice, R., Taliun, D., Olden, M., Foster, M., Yang, Q., Chen, M.H., Pers, T.H., Johnson, A.D., Ko, Y.A., Fuchsberger, C., Tayo, B., Nalls, M., Feitosa, M.F., Isaacs, A., Dehghan, A., d'Adamo, P., Adeyemo, A., Dieffenbach, A.K., Zonderman, A.B., Nolte, I.M., van der Most, P.J., Wright, A.F., Shuldiner, A.R., Morrison, A.C., Hofman, A., Smith, A.V., Dreisbach, A.W., Franke, A., Uitterlinden, A.G., Metspalu, A., Tonjes, A., Lupo, A., Robino, A., Johansson, Å., Demirkan, A., Kollerits, B., Freedman, B.I., Ponte, B., Oostra, B.A., Paulweber, B., Krämer, B.K., Mitchell, B.D., Buckley, B.M., Peralta, C.A., Hayward, C., Helmer, C., Rotimi, C.N., Shaffer, C.M., Müller, C., Sala, C., van Duijn, C.M., Saint-Pierre, A., Ackermann, D., Shriner, D., Ruggiero, D., Toniolo, D., Lu, Y., Cusi, D., Czamara, D., Ellinghaus, D., Siscovick, D.S., Ruderfer, D., Gieger, C., Grallert, H., Rochtchina, E., Atkinson, E.J., Holliday, E.G., Boerwinkle, E., Salvi, E., Bottinger, E.P., Murgia, F., Rivadeneira, F., Ernst, F., Kronenberg, F., Hu, F.B., Navis, G.J., Curhan, G.C., Ehret, G.B., Homuth, G., Coassin, S., Thun, G.A., Pistis, G., Gambaro, G., Malerba, G., Montgomery, G.W., Eiriksdottir, G., Jacobs, G., Li, G., Wichmann, H.E., Campbell, H., Schmidt, H., Wallaschofski, H., Völzke, H., Brenner, H., Kroemer, H.K., Kramer, H., Lin, H., Leach, I.M., Ford, I., Guessous, I., Rudan, I., Prokopenko, I., Borecki, I., Heid, I.M., Kolcic, I., Persico, I., Jukema, J.W., Wilson, J.F., Felix, J.F., Divers, J., Lambert, J.C., Stafford, J.M., Gaspoz, J.M., Smith, J.A., Faul, J.D., Wang, J.J., Ding, J., Hirschhorn, J.N., Attia, J., Whitfield, J.B., Chalmers, J., Viikari, J., Coresh, J., Denny, J.C., Karjalainen, J., Fernandes, J.K., Endlich, K., Butterbach, K., Keene, K.L., Lohman, K., Portas, L., Launer, L.J., Lyytikäinen, L.P., Yengo, L., Franke, L., Ferrucci, L., Rose, L.M., Kedenko, L., Rao, M., Struchalin, M., Kleber, M.E., Cavalieri, M., Haun, M., Cornelis, M.C., Ciullo, M., Pirastu, M., de Andrade, M., McEvoy, M.A., Woodward, M., Adam, M., Cocca, M., Nauck, M., Imboden, M., Waldenberger, M., Pruijm, M., Metzger, M., Stumvoll, M., Evans, M.K., Sale, M.M., Kähönen, M., Boban, M., Bochud, M., Rheinberger, M., Verweij, N., Bouatia-Naji, N., Martin, N.G., Hastie, N., Probst-Hensch, N., Soranzo, N., Devuyst, O., Raitakari, O., Gottesman, O., Franco, O.H., Polasek, O., Gasparini, P., Munroe, P.B., Ridker, P.M., Mitchell, P., Muntner, P., Meisinger, C., Smit, J.H., Kovacs, P., Wild, P.S., Froguel, P., Rettig, R., Mägi, R., Biffar, R., Schmidt, R., Middelberg, R.P., Carroll, R.J., Penninx, B.W., Scott, R.J., Katz, R., Sedaghat, S., Wild, S.H., Kardia, S.L., Ulivi, S., Hwang, S.J., Enroth, S., Kloiber, S., Trompet, S., Stengel, B., Hancock, S.J., Turner, S.T., Rosas, S.E., Stracke, S., Harris, T.B., Zeller, T., Zemunik, T., Lehtimäki, T., Illig, T., Aspelund, T., Nikopensius, T., Esko, T., Gyllensten, U., Völker, U., Emilsson, V., Vitart, V., Aalto, V., Gudnason, V., Chouraki, V., Chen, W.M., Igl, W., März, W., Koenig, W., Lieb, W., Loos, R.J., Liu, Y., Snieder, H., Pramstaller, P.P., Parsa, A., O'Connell, J.R., Susztak, K., Hamet, P., Tremblay, J., de Boer, I.H., Böger, C.A., Goessling, W., Chasman, D.I., Köttgen, A., Kao, W.H., and Fox, C.S.
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

32. Genome-wide association study identifies 74 loci associated with educational attainment

Author: Okbay, Aysu, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, Niels, Turley, P, Chen, GB, Emilsson, V, Meddens, SFW, Oskarsson, S, Pickrell, JK, Thom, K, Timshel, P, Vlaming, Ronald, Abdellaoui, A, Ahluwalia, TS, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Johan, Concas, MP, Derringer, J, Furlotte, NA, Galesloot, TE, Girotto, G, Gupta, R, Hall, LM, Harris, SE, Hofer, E, Horikoshi, M, Huffman, JE, Kaasik, K, Kalafati, IP, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sven, de Leeuw, C, Lind, PA, Lindgren, KO, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, van der Most, PJ, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, WJ, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, KE, Shi, JX, Smith, AV, Poot, Raymond, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N (Niek), Vuckovic, D, Wellmann, J, Westra, HJ, Yang, JY, Zhao, W, Zhu, ZH, Alizadeh, BZ, Amin, Najaf, Bakshi, A, Baumeister, SE, Biino, G, Bonnelykke, K, Boyle, PA, Campbell, H, Cappuccio, FP, Davies, G, De Neve, JE, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, DM, Faul, JD, Feitosa, MF, Forstner, AJ, Gandin, I, Gunnarsson, B, Halldorsson, BV, Harris, TB, Heath, AC, Hocking, LJ, Holliday, EG, Homuth, G, Horan, MA, Hottenga, JJ, De Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kahonen, M, Kanoni, S, Keltigangas-Jarvinen, L, Kiemeney, LALM, Kolcic, I, Koskinen, S, Kraja, AT, Kroh, M, Kutalik, Z, Latvala, A, Launer, LJ, Lebreton, MP, Levinson, DF, Lichtenstein, P, Lichtner, P, Liewald, DCM, Loukola, A, Madden, PA, Magi, R, Maki-Opas, T, Marioni, RE, Marques-Vidal, P, Meddens, GA, McMahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, GW, Myhre, R, Nelson, CP, Nyholt, DR, Ollier, WER, Palotie, A, Paternoster, L, Pedersen, NL, Petrovic, KE, Porteous, DJ, Raikkonen, K, Ring, SM, Robino, A, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, AR, Sarin, AP, Schmidt, Heléna, Scott, RJ, Smith, BH, Smith, JA, Staessen, JA, Steinhagen-Thiessen, E, Strauch, K, Terracciano, A, Tobin, MD, Ulivi, S, Vaccargiu, S, Quaye, L, van Rooij, FJA, Venturini, C, Vinkhuyzen, AAE, Volker, U, Volzke, H, Vonk, JM, Vozzi, D, Waage, J, Ware, EB, Willemsen, G, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Bisgaard, H, Boomsma, DI, Borecki, IB, Bultmann, U, Chabris, CF, Cucca, F, Cusi, D, Deary, IJ, Dedoussis, GV, Duijn, Cornelia, Eriksson, JG, Franke, B, Franke, L, Gasparini, P, Gejman, PV, Gieger, C, Grabe, HJ, Gratten, J, Groenen, Patrick, Gudnason, V, van der Harst, P, Hayward, C, Hinds, DA, Hoffmann, W, Hyppnen, E, Iacono, WG, Jacobsson, B, Jarvelin, MR, Jockel, KH, Kaprio, J, Kardia, SLR, Lehtimaki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Pendleton, N, Penninx, BWJH, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, Daniëlle, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sorensen, TIA, Spector, TD, Stefansson, K, Thorsteinsdottir, U, Thurik, Roy, Timpson, NJ, Tiemeier, Henning, Tung, JY, Uitterlinden, André, Vitart, V, Vollenweider, P, Weir, DR, Wilson, JF, Wright, AF, Conley, DC, Krueger, RF, Smith, GD, Hofman, Bert, Laibson, DI, Medland, SE, Meyer, MN, Yang, Jiaqi, Johannesson, M, Visscher, PM, Esko, T, Koellinger, PD, Cesarini, D, Benjamin, DJ, Okbay, Aysu, Beauchamp, JP, Fontana, MA, Lee, JJ, Pers, TH, Rietveld, Niels, Turley, P, Chen, GB, Emilsson, V, Meddens, SFW, Oskarsson, S, Pickrell, JK, Thom, K, Timshel, P, Vlaming, Ronald, Abdellaoui, A, Ahluwalia, TS, Bacelis, J, Baumbach, C, Bjornsdottir, G, Brandsma, Johan, Concas, MP, Derringer, J, Furlotte, NA, Galesloot, TE, Girotto, G, Gupta, R, Hall, LM, Harris, SE, Hofer, E, Horikoshi, M, Huffman, JE, Kaasik, K, Kalafati, IP, Karlsson, R, Kong, A, Lahti, J, van der Lee, Sven, de Leeuw, C, Lind, PA, Lindgren, KO, Liu, T, Mangino, M, Marten, J, Mihailov, E, Miller, MB, van der Most, PJ, Oldmeadow, C, Payton, A, Pervjakova, N, Peyrot, WJ, Qian, Y, Raitakari, O, Rueedi, R, Salvi, E, Schmidt, B, Schraut, KE, Shi, JX, Smith, AV, Poot, Raymond, St Pourcain, B, Teumer, A, Thorleifsson, G, Verweij, N (Niek), Vuckovic, D, Wellmann, J, Westra, HJ, Yang, JY, Zhao, W, Zhu, ZH, Alizadeh, BZ, Amin, Najaf, Bakshi, A, Baumeister, SE, Biino, G, Bonnelykke, K, Boyle, PA, Campbell, H, Cappuccio, FP, Davies, G, De Neve, JE, Deloukas, P, Demuth, I, Ding, J, Eibich, P, Eisele, L, Eklund, N, Evans, DM, Faul, JD, Feitosa, MF, Forstner, AJ, Gandin, I, Gunnarsson, B, Halldorsson, BV, Harris, TB, Heath, AC, Hocking, LJ, Holliday, EG, Homuth, G, Horan, MA, Hottenga, JJ, De Jager, PL, Joshi, PK, Jugessur, A, Kaakinen, MA, Kahonen, M, Kanoni, S, Keltigangas-Jarvinen, L, Kiemeney, LALM, Kolcic, I, Koskinen, S, Kraja, AT, Kroh, M, Kutalik, Z, Latvala, A, Launer, LJ, Lebreton, MP, Levinson, DF, Lichtenstein, P, Lichtner, P, Liewald, DCM, Loukola, A, Madden, PA, Magi, R, Maki-Opas, T, Marioni, RE, Marques-Vidal, P, Meddens, GA, McMahon, G, Meisinger, C, Meitinger, T, Milaneschi, Y, Milani, L, Montgomery, GW, Myhre, R, Nelson, CP, Nyholt, DR, Ollier, WER, Palotie, A, Paternoster, L, Pedersen, NL, Petrovic, KE, Porteous, DJ, Raikkonen, K, Ring, SM, Robino, A, Rostapshova, O, Rudan, I, Rustichini, A, Salomaa, V, Sanders, AR, Sarin, AP, Schmidt, Heléna, Scott, RJ, Smith, BH, Smith, JA, Staessen, JA, Steinhagen-Thiessen, E, Strauch, K, Terracciano, A, Tobin, MD, Ulivi, S, Vaccargiu, S, Quaye, L, van Rooij, FJA, Venturini, C, Vinkhuyzen, AAE, Volker, U, Volzke, H, Vonk, JM, Vozzi, D, Waage, J, Ware, EB, Willemsen, G, Attia, JR, Bennett, DA, Berger, K, Bertram, L, Bisgaard, H, Boomsma, DI, Borecki, IB, Bultmann, U, Chabris, CF, Cucca, F, Cusi, D, Deary, IJ, Dedoussis, GV, Duijn, Cornelia, Eriksson, JG, Franke, B, Franke, L, Gasparini, P, Gejman, PV, Gieger, C, Grabe, HJ, Gratten, J, Groenen, Patrick, Gudnason, V, van der Harst, P, Hayward, C, Hinds, DA, Hoffmann, W, Hyppnen, E, Iacono, WG, Jacobsson, B, Jarvelin, MR, Jockel, KH, Kaprio, J, Kardia, SLR, Lehtimaki, T, Lehrer, SF, Magnusson, PKE, Martin, NG, McGue, M, Metspalu, A, Pendleton, N, Penninx, BWJH, Perola, M, Pirastu, N, Pirastu, M, Polasek, O, Posthuma, Daniëlle, Power, C, Province, MA, Samani, NJ, Schlessinger, D, Schmidt, R, Sorensen, TIA, Spector, TD, Stefansson, K, Thorsteinsdottir, U, Thurik, Roy, Timpson, NJ, Tiemeier, Henning, Tung, JY, Uitterlinden, André, Vitart, V, Vollenweider, P, Weir, DR, Wilson, JF, Wright, AF, Conley, DC, Krueger, RF, Smith, GD, Hofman, Bert, Laibson, DI, Medland, SE, Meyer, MN, Yang, Jiaqi, Johannesson, M, Visscher, PM, Esko, T, Koellinger, PD, Cesarini, D, and Benjamin, DJ
Abstract: Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals(1). Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample(1,2) of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
Published: 2016

33. Cystatin C and Cardiovascular Disease A Mendelian Randomization Study

Author: van der Laan, SW, Fall, T, Soumare, A, Teumer, A, Sedaghat, Sanaz, Baumert, J, Zabaneh, D, van Setten, J, Isgum, I, Galesloot, TE, Arpegard, J, Amouyel, P, Trompet, S, Waldenberger, M, Dorr, M, Magnusson, PK, Giedraitis, V, Larsson, A, Morris, AP, Felix, Janine, Morrison, AC, Franceschini, N, Bis, JC, Kavousi, Maryam, O'Donnell, C, Drenos, F, Tragante, V, Munroe, PB, Malik, R, Dichgans, M, Worrall, BB, Erdmann, J, Nelson, CP, Samani, NJ, Schunkert, H, Marchini, J, Patel, RS, Hingorani, AD, Lind, L, Pedersen, NL, van der Graaf, J, Kiemeney, LALM, Baumeister, SE, Franco Duran, OH, Hofman, Bert, Uitterlinden, André, Koenig, W, Meisinger, C, Peters, A, Thorand, B, Jukema, JW, Eriksen, B O, Toft, I, Wilsgaard, T, Onland-Moret, NC, van der Schouw, YT, Debette, S, Kumari, M, Svensson, P, van der Harst, P, Kivimaki, M, Keating, BJ, Sattar, N, Dehghan, Abbas, Reiner, AP, Ingelsson, E, den Ruijter, HM, de Bakker, PIW, Pasterkamp, G, Arnlov, J, Holmes, MV, Asselbergs, FW, van der Laan, SW, Fall, T, Soumare, A, Teumer, A, Sedaghat, Sanaz, Baumert, J, Zabaneh, D, van Setten, J, Isgum, I, Galesloot, TE, Arpegard, J, Amouyel, P, Trompet, S, Waldenberger, M, Dorr, M, Magnusson, PK, Giedraitis, V, Larsson, A, Morris, AP, Felix, Janine, Morrison, AC, Franceschini, N, Bis, JC, Kavousi, Maryam, O'Donnell, C, Drenos, F, Tragante, V, Munroe, PB, Malik, R, Dichgans, M, Worrall, BB, Erdmann, J, Nelson, CP, Samani, NJ, Schunkert, H, Marchini, J, Patel, RS, Hingorani, AD, Lind, L, Pedersen, NL, van der Graaf, J, Kiemeney, LALM, Baumeister, SE, Franco Duran, OH, Hofman, Bert, Uitterlinden, André, Koenig, W, Meisinger, C, Peters, A, Thorand, B, Jukema, JW, Eriksen, B O, Toft, I, Wilsgaard, T, Onland-Moret, NC, van der Schouw, YT, Debette, S, Kumari, M, Svensson, P, van der Harst, P, Kivimaki, M, Keating, BJ, Sattar, N, Dehghan, Abbas, Reiner, AP, Ingelsson, E, den Ruijter, HM, de Bakker, PIW, Pasterkamp, G, Arnlov, J, Holmes, MV, and Asselbergs, FW
Published: 2016

34. CHROMOSOME 9P21 LOCUS AND ANGIOGRAPHIC CORONARY ARTERY DISEASE BURDEN: A COLLABORATIVE META-ANALYSIS

Author: Chan, K, Patel, RS, Newcombe, P, Nelson, CP, Qasim, A, Epstein, SE, Burnett, S, Vaccarino, VL, Zafari, AM, Shah, SH, Anderson, JL, Carlquist, JF, Hartiala, J, Allayee, H, Hinohara, K, Lee, BS, Erl, A, Ellis, KL, Goel, A, Schaefer, AS, Mokhtari, NE, Goldstein, BA, Hlatky, MA, Go, AS, Shen, GQ, Gong, Y, Pepine, C, Laxton, RC, Wittaker, JC, Tang, WHW, Johnson, JA, Wang, QK, Assimes, TL, Noethlings, U, Farrall, M, Watkins, H, Richards, AM, Cameron, VA, Muendlein, A, Drexel, H, Koch, W, Park, JE, Kimura, A, Shen, WF, Simpson, IA, Hazen, SL, Horne, BD, Hauser, ER, Quyyumi, AA, Reilly, MP, Samani, NJ, and Ye, S
Published: 2013

35. Identification of seven loci affecting mean telomere length and their association with disease

Author: Codd V, Nelson CP, Albrecht E, Mangino M, Deelen J, Buxton JL, Hottenga JJ, Fischer K, Esko T, Surakka I, Broer L, Nyholt DR, Mateo Leach I, Salo P, Hxe4gg S, Willemsen G, Perola M, Ouwehand W, Kaprio J, Martin NG, van Duijn CM, Hovatta I, Gieger C, Metspalu A, Boomsma DI, Jarvelin MR, Slagboom PE, Thompson JR, Spector TD, van der Harst P, and Samani NJ
Published: 2013

36. Erratum: Meta-analysis of dense genecentric association studies reveals common and uncommon variants associated with height ((The American Journal of Human Genetics (2010) 88 (6-18))

Author: Lanktree, MB, Guo, Y, Murtaza, M, Glessner, JT, Bailey, SD, Onland-Moret, NC, Lettre, G, Ongen, H, Rajagopalan, R, Johnson, T, Shen, H, Nelson, CP, Klopp, N, Baumert, J, Padmanabhan, S, Pankratz, N, Pankow, JS, Shah, S, Taylor, K, Barnard, J, Peters, BJ, Maloney, CM, Lobmeyer, MT, Stanton, A, Zafarmand, MH, Romaine, SPR, Mehta, A, Van Iperen, EPA, Gong, Y, Price, TS, Smith, EN, Kim, CE, Li, YR, Asselbergs, FW, Atwood, LD, Bailey, KM, Bhatt, D, Bauer, F, Behr, ER, Bhangale, T, Boer, JMA, Boehm, BO, Bradfield, JP, Brown, M, Braund, PS, Burton, PR, Carty, C, Chandrupatla, HR, Chen, W, Connell, J, Dalgeorgou, C, De Boer, A, Drenos, F, Elbers, CC, Fang, JC, Fox, CS, Frackelton, EC, Fuchs, B, Furlong, CE, Gibson, Q, Gieger, C, Goel, A, Grobbee, DE, Hastie, C, Howard, PJ, Huang, G-H, Johnson, WC, Li, Q, Kleber, ME, Klein, BEK, Klein, R, Kooperberg, C, Ky, B, Lacroix, A, Lanken, P, Lathrop, M, Li, M, Marshall, V, Melander, O, Mentch, FD, Meyer, NJ, Monda, KL, Montpetit, A, Murugesan, G, Nakayama, K, Nondahl, D, Onipinla, A, Rafelt, S, Newhouse, SJ, Otieno, FG, Patel, SR, Putt, ME, Rodriguez, S, Safa, RN, Sawyer, DB, Schreiner, PJ, Simpson, C, Sivapalaratnam, S, Srinivasan, SR, Suver, C, Swergold, G, Sweitzer, NK, Thomas, KA, Thorand, B, Timpson, NJ, Tischfield, S, Tobin, M, Tomaszewski, M, Verschuren, WMM, Wallace, C, Winkelmann, B, Zhang, H, Zheng, D, Zhang, L, Zmuda, JM, Clarke, R, Balmforth, AJ, Danesh, J, Day, IN, Schork, NJ, De Bakker, PIW, Delles, C, Duggan, D, Hingorani, AD, Hirschhorn, JN, Hofker, MH, Humphries, SE, Kivimaki, M, Lawlor, DA, Kottke-Marchant, K, Mega, JL, Mitchell, BD, Morrow, DA, Palmen, J, Redline, S, Shields, DC, Shuldiner, AR, Sleiman, PM, Smith, GD, Farrall, M, Jamshidi, Y, Christiani, DC, Casas, JP, Hall, AS, Doevendans, PA, Christie, JD, Berenson, GS, Murray, SS, Illig, T, Dorn, GW, Cappola, TP, Boerwinkle, E, Sever, P, Rader, DJ, Reilly, MP, Caulfield, M, Talmud, PJ, Topol, E, Engert, JC, Wang, K, Dominiczak, A, Hamsten, A, Curtis, SP, Silverstein, RL, Lange, LA, Sabatine, MS, Trip, M, Saleheen, D, Peden, JF, Cruickshanks, KJ, März, W, O'Connell, JR, Klungel, OH, Wijmenga, C, Maitland-Van Der Zee, AH, Schadt, EE, Johnson, JA, Jarvik, GP, Papanicolaou, GJ, Grant, SFA, Munroe, PB, North, KE, Samani, NJ, Koenig, W, Gaunt, TR, Anand, SS, Van Der Schouw, YT, Soranzo, N, Fitzgerald, GA, Reiner, A, Hegele, RA, Hakonarson, H, and Keating, BJ
Published: 2012

37. Erratum: Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci (American Journal of Human Genetics (2012) 90 (410-425))

Author: Saxena, R, Elbers, CC, Guo, Y, Peter, I, Gaunt, TR, Mega, JL, Lanktree, MB, Tare, A, Castillo, BA, Li, YR, Johnson, T, Bruinenberg, M, Gilbert-Diamond, D, Rajagopalan, R, Voight, BF, Balasubramanyam, A, Barnard, J, Bauer, F, Baumert, J, Bhangale, T, Böhm, BO, Braund, PS, Burton, PR, Chandrupatla, HR, Clarke, R, Cooper-Dehoff, RM, Crook, ED, Davey-Smith, G, Day, IN, De Boer, A, De Groot, MCH, Drenos, F, Ferguson, J, Fox, CS, Furlong, CE, Gibson, Q, Gieger, C, Gilhuijs-Pederson, LA, Glessner, JT, Goel, A, Gong, Y, Grant, SFA, Grobbee, DE, Hastie, C, Humphries, SE, Kim, CE, Kivimaki, M, Kleber, M, Meisinger, C, Kumari, M, Langaee, TY, Lawlor, DA, Li, M, Lobmeyer, MT, Maitland-Van Der Zee, A-H, Meijs, MFL, Molony, CM, Morrow, DA, Murugesan, G, Musani, SK, Nelson, CP, Newhouse, SJ, O'Connell, JR, Padmanabhan, S, Palmen, J, Patel, SR, Pepine, CJ, Pettinger, M, Price, TS, Rafelt, S, Ranchalis, J, Rasheed, A, Rosenthal, E, Ruczinski, I, Shah, S, Shen, H, Silbernagel, G, Smith, EN, Spijkerman, AWM, Stanton, A, Steffes, MW, Thorand, B, Trip, M, Van Der Harst, P, Van Der A, DL, Van Iperen, EPA, Van Setten, J, Van Vliet-Ostaptchouk, JV, Verweij, N, Wolffenbuttel, BHR, Young, T, Hadi Zafarmand, M, Zmuda, JM, Boehnke, M, Altshuler, D, McCarthy, M, Linda Kao, WH, Pankow, JS, Cappola, TP, Sever, P, Poulter, N, Caulfield, M, Dominiczak, A, Shields, DC, Bhatt, DL, Zhang, L, Curtis, SP, Danesh, J, Casas, JP, Van Der Schouw, YT, Onland-Moret, NC, Doevendans, PA, Dorn II, GW, Farrall, M, Fitzgerald, GA, Robert Hegele, AH, Hingorani, AD, Hofker, MH, Huggins, GS, Illig, T, Jarvik, GP, Johnson, JA, Klungel, OH, Knowler, WC, Koenig, W, März, W, Meigs, JB, Melander, O, Munroe, PB, Mitchell, BD, Bielinski, SJ, Rader, DJ, Reilly, MP, Rich, SS, Rotter, JI, Saleheen, D, Samani, NJ, Schadt, EE, Shuldiner, AR, Silverstein, R, Kottke-Marchant, K, Talmud, PJ, Watkins, H, Asselbergs, FW, De Bakker, PIW, McCaffery, J, Wijmenga, C, Sabatine, MS, Wilson, JG, Reiner, A, Bowden, DW, Hakonarson, H, Siscovick, DS, and Keating, BJ
Published: 2012

38. Homocysteine and coronary heart disease: Meta-analysis of MTHFR case-control studies, avoiding publication bias

Author: Holm, H, Thorsteinsdottir, U, Gretarsdottir, S, Gulcher, Jr, Thorgeirsson, G, Andersen, K, Stefansson, K, Parish, S, Bennett, Da, Clarke, R, Peto, R, Sleight, P, Collins, R, Hopewell, Jc, Watkins, H, Saleheen, D, Danesh, J, Rasheed, A, Zaidi, M, Frossard, P, Shah, N, Samuel, M, Tanaka, T, Ozaki, K, Sato, H, Sakata, Y, Komuro, I, Anand, Ss, Yusuf, S, Engert, Jc, Chambers, J, Kooner, J, Armitage, J, Samani, Nj, Braund, Ps, Nelson, Cp, Hall, As, Balmforth, A, Ball, Sg, Kleber, Me, Hoffmann, Mm, März, Wa, Bugert, P, Winkelmann, B, Böhm, Bo, Ouwehand, Wh, Sivapalaratnam, S, Kastelein, Jj, Trip, Md, Bezzina, Cr, Ouwehand, W, Yamada, Y, Elbers, Cc, Onland Moret NC, Bauer, F, van der Schouw YT, Verschuren, Wm, de Boer JM, Wijmenga, C, Hofker, Mh, de Bakker PI, Peters, Bj, Maitland van der Zee AH, de Boer, A, Klungel, Oh, Grobbee, De, Stewart, Af, Roberts, R, Mcpherson, R, Chen, L, Wells, Ga, Reilly, Mm, Li, M, Qu, I, Rader, Dj, Thorand, B, Illig, T, Peters, A, Koenig, W, Assimes, Tl, Fortmann, S, Iribarren, C, Abbate, R, Marcucci, R, Anderson, Jl, Zebrack, Js, Ardissino, D, Merlini, Fm, Bonomi, Ab, Ashfield Watt PA, Clark, Ze, van Bockxmeer FM, Brownrigg, L, Kooner, Js, Ferrer Antunes, C, Palmeiro, A, Fernandez Arcas, N, Reyes Engel, A, Folsom, Ar, Fowkes, Fg, Lee, Aj, Gaziano, Jm, Gemmati, D, Scapoli, Gl, Genest, J, Rozen, R, Girelli, Domenico, Corrocher, Roberto, Rossi, Gb, Meleady, R, Graham, Im, Gulec, S, Hopkins, Pn, Inbal, A, Selighson, U, Jukema, Jw, Litynsky, P, Kluijtmans, La, Kozich, V, Janosikova, B, Ma, J, Stampfer, Mj, Malinow, Mr, Meisel, C, Stangl, K, Morita, H, Nagai, R, Nakai, K, Nordestgaard, Bg, Zacho, J, Rimm, Eb, Schwartz, Sm, Siscovick, Ds, Silberberg, Js, Szczeklik, A, Domagala, Bt, Tanis, Bc, Rosendaal, Fm, Thogersen, Am, Nilsson, Tk, Todesco, L, Tokgozoglu, Sl, Tsai, My, Hanson, Nq, Verhoeff, Bj, Yamakawa Kobayashi, K, Hamaguchi, H., Medical Research Council (MRC), Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Pulmonology, and Other departments
Subjects: Homocysteine, coronary heart disease, methylene tetrahydrofolate reductase, Coronary Disease, FOLIC-ACID, 030204 cardiovascular system & hematology, PLACEBO-CONTROLLED TRIAL, Gastroenterology, Methylenetetrahydrofolate reductase gene, Placebo-controlled trial, Cardiovascular-disease, Mendelian randomization, Myocardial-infarction, Vascular-disease, Common mutation, B vitamins, Folic-acid, Ethnic-groups, chemistry.chemical_compound, MTHFR, risk factors, publication bias, GWA, genome-wide association, meta-analysis, 0302 clinical medicine, Polymorphism (computer science), 030212 general & internal medicine, Myocardial infarction, 11 Medical and Health Sciences, Genetics, biology, VASCULAR-DISEASE, General Medicine, ETHNIC-GROUPS, 3. Good health, CARDIOVASCULAR-DISEASE, Meta-analysis, MENDELIAN RANDOMIZATION, Medicine, MTHFR Studies Collaborative Group, Life Sciences & Biomedicine, Research Article, medicine.medical_specialty, Genotype, METHYLENETETRAHYDROFOLATE REDUCTASE GENE, Genomic disorders and inherited multi-system disorders [IGMD 3], 03 medical and health sciences, Medicine, General & Internal, Folic Acid, Bias, Internal medicine, General & Internal Medicine, medicine, Humans, Methylenetetrahydrofolate Reductase (NADPH2), Science & Technology, Polymorphism, Genetic, business.industry, Case-control study, Odds ratio, Publication bias, medicine.disease, COMMON MUTATION, chemistry, MYOCARDIAL-INFARCTION, Methylenetetrahydrofolate reductase, biology.protein, B VITAMINS, business
Abstract: Robert Clarke and colleagues conduct a meta-analysis of unpublished datasets to examine the causal relationship between elevation of homocysteine levels in the blood and the risk of coronary heart disease. Their data suggest that an increase in homocysteine levels is not likely to result in an increase in risk of coronary heart disease., Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR, Editors' Summary Background Coronary heart disease (CHD) is the leading cause of death among adults in developed countries. With age, fatty deposits (atherosclerotic plaques) coat the walls of the coronary arteries, the blood vessels that supply the heart with oxygen and nutrients. The resultant restriction of the heart's blood supply causes shortness of breath, angina (chest pains that are usually relieved by rest), and sometimes fatal heart attacks. Many established risk factors for CHD, including smoking, physical inactivity, being overweight, and eating a fat-rich diet, can be modified by lifestyle changes. Another possible modifiable risk factor for CHD is a high blood level of the amino acid homocysteine. Methylene tetrahydofolate reductase, which is encoded by the MTHFR gene, uses folate to break down and remove homocysteine so fortification of cereals with folate can reduce population homocysteine blood levels. Pooled results from prospective observational studies that have looked for an association between homocysteine levels and later development of CHD suggest that the reduction in homocysteine levels that can be achieved by folate supplementation is associated with an 11% lower CHD risk. Why Was This Study Done? Prospective observational studies cannot prove that high homocysteine levels cause CHD because of confounding, the potential presence of other unknown shared characteristics that really cause CHD. However, an approach called “Mendelian randomization” can test whether high blood homocysteine causes CHD. A common genetic variant of the MTHFR gene—the C677T polymorphism—reduces MTHFR efficiency so TT homozygotes (individuals in whom both copies of the MTHFR gene have the nucleotide thymine at position 677; the human genome contains two copies of most genes) have 25% higher blood homocysteine levels than CC homozygotes. In meta-analyses (statistical pooling of the results of several studies) of published Mendelian randomized studies, TT homozygotes have a higher CHD risk than CC homozygotes. Because gene variants are inherited randomly, they are not subject to confounding, so this result suggests that high blood homocysteine causes CHD. But what if only Mendelian randomization studies that found an association have been published? Such publication bias would affect this aggregate result. Here, the researchers investigate the association of the MTHFR C677T polymorphism with CHD in unpublished datasets that have analyzed this polymorphism incidentally during other genetic studies. What Did the Researchers Do and Find? The researchers obtained 19 unpublished datasets that contained data on the MTHFR C677T polymorphism in thousands of people with and without CHD. Meta-analysis of these datasets indicates that the excess CHD risk in TT homozygotes compared to CC homozygotes was 2% (much lower than predicted from the prospective observational studies), a nonsignificant difference (that is, it could have occurred by chance). When the probable folate status of the study populations (based on when national folic acid fortification legislation came into effect) was taken into account, there was still no evidence that TT homozygotes had an excess CHD risk. By contrast, in an updated meta-analysis of 86 published studies of the association of the polymorphism with CHD, the excess CHD risk in TT homozygotes compared to CC homozygotes was 15%. Finally, in a meta-analysis of randomized trials on the use of vitamin B supplements for homocysteine reduction, folate supplementation had no significant effect on the 5-year incidence of CHD. What Do These Findings Mean? These analyses of unpublished datasets are consistent with lifelong moderate elevation of homocysteine levels having no significant effect on CHD risk. In other words, these findings indicate that circulating homocysteine levels within the normal range are not causally related to CHD risk. The meta-analysis of the randomized trials of folate supplementation also supports this conclusion. So why is there a discrepancy between these findings and those of meta-analyses of published Mendelian randomization studies? The discrepancy is too large to be dismissed as a chance finding, suggest the researchers, but could be the result of publication bias—some studies might have been prioritized for publication because of the positive nature of their results whereas the unpublished datasets used in this study would not have been affected by any failure to publish null results. Overall, these findings reveal a serious example of publication bias and argue against the use of folate supplements as a means of reducing CHD risk. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001177. The American Heart Association provides information about CHD and tips on keeping the heart healthy; it also provides information on homocysteine, folic acid, and CHD, general information on supplements and heart health, and personal stories about CHD The UK National Health Service Choices website provides information about CHD, including personal stories about CHD Information is available from the British Heart Foundation on heart disease and keeping the heart healthy The US National Heart Lung and Blood Institute also provides information on CHD (in English and Spanish) MedlinePlus provides links to many other sources of information on CHD (in English and Spanish) Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Published: 2012

39. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure

Author: Wain, LV, Verwoert, GC, O'Reilly, PF, Shi, G, Johnson, T, Johnson, AD, Bochud, M, Rice, KM, Henneman, P, Smith, AV, Ehret, GB, Amin, N, Larson, MG, Mooser, V, Hadley, D, Dörr, M, Bis, JC, Aspelund, T, Esko, T, Janssens, AC, Zhao, JH, Heath, S, Laan, M, Fu, J, Pistis, G, Luan, J, Arora, P, Lucas, G, Pirastu, N, Pichler, I, Jackson, AU, Webster, RJ, Zhang, F, Peden, JF, Schmidt, H, Tanaka, T, Campbell, H, Igl, W, Milaneschi, Y, Hottenga, JJ, Vitart, V, Chasman, DI, Trompet, S, Bragg-Gresham, JL, Alizadeh, BZ, Chambers, JC, Guo, X, Lehtimäki, T, Kühnel, B, Lopez, LM, Polašek, O, Boban, M, Nelson, CP, Morrison, AC, Pihur, V, Ganesh, SK, Hofman, A, Kundu, S, Mattace-Raso, FU, Rivadeneira, F, Sijbrands, EJ, Uitterlinden, AG, Hwang, SJ, Vasan, RS, Wang, TJ, Bergmann, S, Vollenweider, P, Waeber, G, Laitinen, J, Pouta, A, Zitting, P, McArdle, WL, Kroemer, HK, Völker, U, Völzke, H, Glazer, NL, Taylor, KD, Harris, TB, Alavere, H, Haller, T, Keis, A, Tammesoo, ML, Aulchenko, Y, Barroso, I, Khaw, KT, Galan, P, Hercberg, S, Lathrop, M, Eyheramendy, S, Org, E, Sõber, S, Lu, X, Nolte, IM, Penninx, BW, Corre, T, Masciullo, C, Sala, C, Groop, L, Voight, BF, Melander, O, O'Donnell, CJ, Salomaa, V, d'Adamo, AP, Fabretto, A, Faletra, F, Ulivi, S, Del Greco, F, Facheris, M, Collins, FS, Bergman, RN, Beilby, JP, Hung, J, Musk, AW, Mangino, M, Shin, SY, Soranzo, N, Watkins, H, Goel, A, Hamsten, A, Gider, P, Loitfelder, M, Zeginigg, M, Hernandez, D, Najjar, SS, Navarro, P, Wild, SH, Corsi, AM, Singleton, A, de Geus, EJ, Willemsen, G, Parker, AN, Rose, LM, Buckley, B, Stott, D, Orru, M, Uda, M, LifeLines Cohort Study, van der Klauw, MM, Zhang, W, Li, X, Scott, J, Chen, YD, Burke, GL, Kähönen, M, Viikari, J, Döring, A, Meitinger, T, Davies, G, Starr, JM, Emilsson, V, Plump, A, Lindeman, JH, Hoen, PA, König, IR, EchoGen consortium, Felix, JF, Clarke, R, Hopewell, JC, Ongen, H, Breteler, M, Debette, S, Destefano, AL, Fornage, M, AortaGen Consortium, Mitchell, GF, CHARGE Consortium Heart Failure Working Group, Smith, NL, KidneyGen consortium, Holm, H, Stefansson, K, Thorleifsson, G, Thorsteinsdottir, U, CKDGen consortium, Cardiogenics consortium, CardioGram, Samani, NJ, Preuss, M, Rudan, I, Hayward, C, Deary, IJ, Wichmann, HE, Raitakari, OT, Palmas, W, Kooner, JS, Stolk, RP, Jukema, JW, Wright, AF, Boomsma, DI, Bandinelli, S, Gyllensten, UB, Wilson, JF, Ferrucci, L, Schmidt, R, Farrall, M, Spector, TD, Palmer, LJ, Tuomilehto, J, Pfeufer, A, Gasparini, P, Siscovick, D, Altshuler, D, Loos, RJ, Toniolo, D, Snieder, H, Gieger, C, Meneton, P, Wareham, NJ, Oostra, BA, Metspalu, A, Launer, L, Rettig, R, Strachan, DP, Beckmann, JS, Witteman, JC, Erdmann, J, van Dijk, KW, Boerwinkle, E, Boehnke, M, Ridker, PM, Jarvelin, MR, Chakravarti, A, Abecasis, GR, Gudnason, V, Newton-Cheh, C, Levy, D, Munroe, PB, Psaty, BM, Caulfield, MJ, Rao, DC, Tobin, MD, Elliott, P, and van Duijn, CM
Published: 2011

40. 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, 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, Voight BF, Florez J. C., 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, Hofmann, Om, Qi, L, Segrè, Av, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, Aj, Blagieva, R, Boerwinkle, E, Bonnycastle, Ll, Bengtsson Boström, K, Bravenboer, B, Bumpstead, S, Burtt, P, Charpentier, G, Chines, Ps, Cornelis, M, Couper, Dj, Crawford, G, Doney, As, Elliott, Ks, Elliott, Al, Erdos, Mr, Franklin, Cs, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, Cj, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Johnson, Pr, Jørgensen, T, Kao, Wh, Klopp, N, Kong, A, Kraft, P, Lauritzen, T, Li, M, Lieverse, A, Lindgren, Cm, Marre, M, Meitinger, T, Midthjell, K, Morken, Ma, Nilsson, P, Owen, Kr, Perry, Jr, Petersen, K, Platou, C, Proença, C, Rathmann, W, William Rayner, N, Robertson, Nr, Rocheleau, G, Roden, M, Sampson, Mj, Saxena, R, Shields, Bm, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, Hm, Sun, Q, Thorand, B, Tichet, J, van Dam RM, van Haeften TW, van Herpt, T, van Vliet JV, Bragi Walters, G, Wijmenga, C, Witteman, J, Bergman, Rn, Cauchi, S, Gyllensten, U, Hansen, T, Hide, Wa, Hitman, Ga, Hofman, A, Hunter, Dj, Hveem, K, Mohlke, Kl, Morris, Ad, Palmer, Cn, Pramstaller, Pp, Rudan, I, Sijbrands, E, Stein, Ld, Tuomilehto, J, Uitterlinden, A, Abecasis, Gr, Boehm, Bo, Campbell, H, Daly, Mj, Hattersley, At, Hu, Fb, Pankow, Js, Pedersen, O, Wichmann, E, Florez, Jc, Sladek, R, Thorsteinsdottir, U, Wilson, Jf, Illig, T, Stefansson, K, Altshuler, D, Speliotes, Ek, Berndt, Si, Monda, Kl, Allen, Hl, Mägi, R, Randall, Jc, Vedantam, S, Winkler, Tw, Workalemahu, T, Heid, Im, Wood, Ar, Weyant, Rj, Estrada, K, Liang, L, Nemesh, J, Park, Jh, Kilpeläinen, To, Yang, J, Esko, T, Feitosa, Mf, Kutalik, Z, Mangino, M, Scherag, A, Smith, Av, Welch, R, Zhao, Jh, Aben, Kk, Absher, Dm, Dixon, Al, Fisher, E, Glazer, Nl, Goddard, Me, Heard Costa NL, Hoesel, V, Hottenga, Jj, Johansson, Å, Johnson, T, Ketkar, S, Lamina, C, Li, S, Moffatt, Mf, Myers, Rh, Peters, Mj, Preuss, M, Ripatti, S, Rivadeneira, F, Sandholt, C, Timpson, Nj, Tyrer, Jp, van Wingerden, S, White, Cc, Wiklund, F, Barlassina, C, Chasman, Di, Cooper, Mn, Jansson, Jo, Lawrence, Rw, Pellikka, N, Shi, J, Thiering, E, Alavere, H, Alibrandi, Mt, Arnold, Am, Aspelund, T, Atwood, Ld, Balmforth, Aj, Ben Shlomo, Y, Bergmann, S, Biebermann, H, Blakemore, Ai, Boes, T, Bornstein, Sr, Brown, Mj, Buchanan, Ta, Busonero, F, Cappuccio, Fp, Cavalcanti Proença, C, Ida Chen YD, Chen, Cm, Coin, L, Connell, J, Day, In, den Heijer, M, Duan, J, Ebrahim, S, Elliott, P, Elosua, R, Eiriksdottir, G, Facheris, Mf, Felix, Sb, Fischer Posovszky, P, Folsom, Ar, Friedrich, N, Freimer, Nb, Fu, M, Gaget, S, Gejman, Pv, Geus, Ej, Gjesing, Ap, Goyette, P, Grässler, J, Greenawalt, Dm, Gudnason, V, Hartikainen, Al, Hall, As, Havulinna, As, Hayward, C, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hinney, A, Homuth, G, Hui, J, Igl, W, Iribarren, C, Jacobs, Kb, Jarick, I, Jewell, E, John, U, Jousilahti, P, Jula, A, Kaakinen, M, Kaplan, Lm, Kathiresan, S, Kettunen, J, Kinnunen, L, Knowles, Jw, Kolcic, I, König, Ir, Koskinen, S, Kovacs, P, Kvaløy, K, Laitinen, J, Lantieri, O, Lanzani, C, Launer, Lj, Lecoeur, C, Terho, L, Lettre, G, Liu, J, Lokki, Ml, Lorentzon, M, Luben, Rn, Ludwig, B, Magic, Manunta, P, Marek, D, Martin, Ng, Mcardle, Wl, Mccarthy, A, Mcknight, B, Melander, O, Meyre, D, Montgomery, Gw, Mulic, R, Ngwa, Js, Nelis, M, Neville, Mj, Nyholt, Dr, O'Donnell, Cj, O'Rahilly, S, Ong, Kk, Oostra, B, Paré, G, Parker, An, Perola, M, Pichler, I, Pietiläinen, Kh, Platou, Cg, Polasek, O, Pouta, A, Rafelt, S, Raitakari, O, Rayner, Nw, Ridderstråle, M, Rief, W, Ruokonen, A, Rzehak, P, Salomaa, V, Sanders, Ar, Sandhu, Ms, Sanna, S, Saramies, J, Savolainen, Mj, Scherag, S, Schipf, S, Schreiber, S, Schunkert, H, Silander, K, Sinisalo, J, Siscovick, Ds, Smit, Jh, Soranzo, N, Sovio, U, Stephens, J, Surakka, I, Tammesoo, Ml, Tardif, Jc, Teder Laving, M, Teslovich, Tm, Thompson, Jr, Thomson, B, Tönjes, A, van Meurs JB, van Ommen GJ, Vatin, V, Viikari, J, Visvikis Siest, S, Vitart, V, Vogel, Ci, Waite, Ll, Wallaschofski, H, Walters, Gb, Widen, E, Wiegand, S, Wild, Sh, Willemsen, G, Witte, Dr, Witteman, Jc, Xu, J, Zhang, Q, Zgaga, L, Ziegler, A, Zitting, P, Beilby, Jp, Farooqi, Is, Hebebrand, J, Huikuri, Hv, James, Al, Kähönen, M, Levinson, Df, Macciardi, F, Nieminen, Ms, Ohlsson, C, Palmer, Lj, Ridker, Pm, Stumvoll, M, Beckmann, Js, Boeing, H, Dorret, I. B., Caulfield, Mj, Chanock, Sj, Cupples, La, Smith, Gd, Erdmann, J, Grönberg, H, Hall, P, Harris, Tb, Hayes, Rb, Heinrich, J, Jarvelin, Mr, Kaprio, J, Karpe, F, Khaw, Kt, Kiemeney, La, Krude, H, Lawlor, Da, Metspalu, A, Munroe, Pb, Ouwehand, Wh, Penninx, Bw, Peters, A, Quertermous, T, Reinehr, T, Rissanen, A, Samani, Nj, Schwarz, Pe, Shuldiner, Ar, Spector, Td, Uda, M, Valle, Tt, Wabitsch, M, Waeber, G, Shaun, P, Eric, E. S., Peter, M. V., Assimes, Tl, Borecki, Ib, Groop, Lc, Haritunians, T, Kaplan, Rc, O'Connell, Jr, Peltonen, L, Schlessinger, D, Strachan, Dp, van Duijn CM, Barroso, H, North, Ke, Hirschhorn, Jn, Nica, Ac, Parts, L, Glass, D, Nisbet, J, Barrett, A, Sekowska, M, Travers, M, Potter, S, Grundberg, E, Small, K, Hedman, Åk, Bataille, V, Bell, Jt, Surdulescu, G, Ingle, C, Nestle, Fo, di Meglio, P, Min, Jl, Wilk, A, Hammond, Cj, Yang, Tp, Montgomery, Sb, Zondervan, Kt, Durbin, R, Ahmadi, K, Reilly, Mp, Holm, H, Stewart, Af, Barbalic, M, Absher, D, Aherrahrou, Z, Allayee, H, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Braund, Ps, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, El Mokhtari NE, Ellis, Sg, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Horne, Bd, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kastelein, Jj, Kolovou, G, Laaksonen, R, Lambrechts, D, Leander, K, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Sampietro, Ml, Schadt, E, Schäfer, A, Schillert, A, Schrezenmeir, J, Schwartz, Sm, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Spertus, Ja, Stark, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Wright, Bj, Ye, S, Zeller, T, Cambien, F, Goodall, Ah, März, W, Blankenberg, S, Roberts, R, Mcpherson, R, Nilesh, J. S., Medical Research Council (MRC), Nica, Alexandra, Ongen, Halit, Dermitzakis, Emmanouil, ACS - Amsterdam Cardiovascular Sciences, Cardiology, Vascular Medicine, Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Scherag, Andre (Beitragende*r), Hinney, Anke (Beitragende*r), Scherag, S. (Beitragende*r), Vogel, C (Beitragende*r), Hebebrand, Johannes (Beitragende*r), University of Groningen, Wheeler, Eleanor [0000-0002-8616-6444], Barnes, Daniel [0000-0002-3781-7570], Luan, Jian'an [0000-0003-3137-6337], Johnson, Kathleen [0000-0002-6823-3252], Danesh, John [0000-0003-1158-6791], Wareham, Nicholas [0000-0003-1422-2993], Barroso, Ines [0000-0001-5800-4520], Langenberg, Claudia [0000-0002-5017-7344], and Apollo - University of Cambridge Repository
Subjects: Male, Netherlands Twin Register (NTR), endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medizin, Genome-wide association study, Type 2 diabetes, CORONARY HEART-DISEASE, Fasting/blood, 0302 clinical medicine, Insulin, Glucose homeostasis, ddc:576.5, Genome-wide, Diabetes Mellitus, Type 2/blood/genetics/metabolism, CARDIoGRAM Consortium, POPULATION, Proinsulin, RISK, Genetics, 0303 health sciences, INSULIN SENSITIVITY, 11 Medical And Health Sciences, Fasting, Polymorphism, Single Nucleotide/genetics, OBESITY, Female, type 2 diabetes, Life Sciences & Biomedicine, hormones, hormone substitutes, and hormone antagonists, Insulin processing, Adult, medicine.medical_specialty, endocrine system, ENDOCRINOLOGY & METABOLISM, SUSCEPTIBILITY LOCI, Genotype, 030209 endocrinology & metabolism, DIAGRAM Consortium, Biology, C4D Consortium, Polymorphism, Single Nucleotide, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, Insulin resistance, BETA-CELL FUNCTION, SDG 3 - Good Health and Well-being, Internal medicine, GIANT Consortium, Internal Medicine, medicine, Humans, METAANALYSIS, 030304 developmental biology, Science & Technology, Genome, Human, Hormonal regulation [IGMD 6], Genetic Variation, nutritional and metabolic diseases, proinsulin, medicine.disease, Proinsulin/blood, TCF7L2, Endocrinology, Diabetes Mellitus, Type 2, MuTHER Consortium, GLUCOSE-HOMEOSTASIS, Insulin/blood
Abstract: OBJECTIVE Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10−8). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10−4), improved β-cell function (P = 1.1 × 10−5), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10−6). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.
Published: 2011
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41. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

Author: Schunkert, H, König, Ir, Kathiresan, S, Reilly, Mp, Assimes, Tl, Holm, H, Preuss, M, Stewart, Af, Barbalic, M, Gieger, C, Absher, D, Aherrahrou, Z, Allayee, H, Altshuler, D, Anand, Ss, Andersen, K, Anderson, Jl, Ardissino, D, Ball, Sg, Balmforth, Aj, Barnes, Ta, Becker, Dm, Becker, Lc, Berger, K, Bis, Jc, Boekholdt, Sm, Boerwinkle, E, Braund, Ps, Brown, Mj, Burnett, Ms, Buysschaert, I, Cardiogenics, Carlquist, Jf, Chen, L, Cichon, S, Codd, V, Davies, Rw, Dedoussis, G, Dehghan, A, Demissie, S, Devaney, Jm, Diemert, P, Do, R, Doering, A, Eifert, S, Mokhtari, Ne, Ellis, Sg, Elosua, R, Engert, Jc, Epstein, Se, de Faire, U, Fischer, M, Folsom, Ar, Freyer, J, Gigante, B, Girelli, Domenico, Gretarsdottir, S, Gudnason, V, Gulcher, Jr, Halperin, E, Hammond, N, Hazen, Sl, Hofman, A, Horne, Bd, Illig, T, Iribarren, C, Jones, Gt, Jukema, Jw, Kaiser, Ma, Kaplan, Lm, Kastelein, Jj, Khaw, Kt, Knowles, Jw, Kolovou, G, Kong, A, Laaksonen, R, Lambrechts, D, Leander, K, Lettre, G, Li, M, Lieb, W, Loley, C, Lotery, Aj, Mannucci, Pm, Maouche, S, Martinelli, Nicola, Mckeown, Pp, Meisinger, C, Meitinger, T, Melander, O, Merlini, Pa, Mooser, V, Morgan, T, Mühleisen, Tw, Muhlestein, Jb, Münzel, T, Musunuru, K, Nahrstaedt, J, Nelson, Cp, Nöthen, Mm, Olivieri, Oliviero, Patel, Rs, Patterson, Cc, Peters, A, Peyvandi, F, Qu, L, Quyyumi, Aa, Rader, Dj, Rallidis, Ls, Rice, C, Rosendaal, Fr, Rubin, D, Salomaa, V, Sampietro, Ml, Sandhu, Ms, Schadt, E, Schäfer, A, Schillert, A, Schreiber, S, Schrezenmeir, J, Schwartz, Sm, Siscovick, Ds, Sivananthan, M, Sivapalaratnam, S, Smith, A, Smith, Tb, Snoep, Jd, Soranzo, N, Spertus, Ja, Stark, K, Stirrups, K, Stoll, M, Tang, Wh, Tennstedt, S, Thorgeirsson, G, Thorleifsson, G, Tomaszewski, M, Uitterlinden, Ag, van Rij AM, Voight, Bf, Wareham, Nj, Wells, Ga, Wichmann, He, Wild, Ps, Willenborg, C, Witteman, Jc, Wright, Bj, Ye, S, Zeller, T, Ziegler, A, Cambien, F, Goodall, Ah, Cupples, La, Quertermous, T, März, W, Hengstenberg, C, Blankenberg, S, Ouwehand, Wh, Hall, As, Deloukas, P, Thompson, Jr, Stefansson, K, Roberts, R, Thorsteinsdottir, U, O'Donnell, Cj, Mcpherson, R, Erdmann, J, the CARDIoGRAM Consortium, Samani, N. J., Epidemiology, Internal Medicine, ACS - Amsterdam Cardiovascular Sciences, Cardiology, and Vascular Medicine
Subjects: Adult, Male, Multifunction cardiogram, Locus (genetics), Single-nucleotide polymorphism, Genome-wide association study, Coronary Artery Disease, Biology, Polymorphism, Single Nucleotide, Genetic determinism, artery disease, Article, Coronary artery disease, Gene Frequency, SDG 3 - Good Health and Well-being, Risk Factors, Genetics, medicine, Humans, Genetic Predisposition to Disease, cardiovascular diseases, Allele, Genotyping, Allele frequency, coronary, Alleles, Genetics (clinical), Aged, Genetic association, business.industry, Case-control study, Middle Aged, medicine.disease, coronary artery disease, Large-scale association analysis, Case-Control Studies, Female, Cardiology and Cardiovascular Medicine, business, Genome-Wide Association Study
Abstract: 1. The CARDIoGRAM Consortium. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nature Genetics. 2011;43:333–338. ### Study Hypothesis Recently, genome-wide association studies (GWAS) have identified several common variants that are associated with risk of coronary artery disease (CAD) and myocardial infarction (MI). The authors state that the current loci discovered in CAD and MI GWAS explain only a small fraction of the heritability of this complex disease. The authors hypothesized that a larger study would provide more power to discover common variants with modest effect sizes. Therefore, they formed the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium, which consisted of data from 14 GWAS of CAD and MI.1 ### How Was the Hypothesis Tested? The authors performed a meta-analysis of 14 GWAS of CAD comprising 22 233 cases and 64 762 control subjects, all of European ancestry. CAD was defined angiographically in a subset (n=7364) and by history in the entire sample. Presence of MI ranged from 48.1% to 100% of each cohort. After the meta-analysis, they genotyped the lead single-nucleotide polymorphisms (SNPs) within the most promising (defined a priori as P 90% power to detect effect sizes observed in the GWAS meta-analysis. Finally, to understand potential mechanisms and intermediate pathways by which novel loci may mediate risk, the authors interrogated 3 genome-wide studies that also assessed gene expression in multiple tissues, using human cell lines, a genome-wide map of allelic expression imbalance, and other human disease traits. ### Principal Findings The analysis of approximately 135 000 individuals more than doubled the number of loci with CAD association, yielding 13 previously unidentified loci and confirming at …
Published: 2011

42. Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis

Author: Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, Danesh, J, Freitag, DF, Butterworth, AS, Willeit, P, Howson, JMM, Burgess, S, Kaptoge, S, Young, R, Ho, WK, Wood, AM, Sweeting, M, Spackman, S, Staley, JR, Ramond, A, Harshfield, E, Nielsen, SF, Grande, P, Lange, LA, Bown, MJ, Jones, GT, Scott, RA, Bevan, S, Porcu, E, Thorleifsson, G, Zeng, LY, Kessler, T, Nikpay, M, Do, R, Zhang, WH, Hopewell, JC, Kleber, M, Delgado, GE, Nelson, CP, Goel, A, Bis, JC, Dehghan, Abbas, Ligthart, Symen, Smith, AV, Qu, LM, van 't Hof, FNG, de Bakker, PIW, Baas, AF, van Rij, A, Tromp, G, Kuivaniemi, H, Ritchie, MD, Verma, SS, Crawford, DC, Malinowski, J, de Andrade, M, Kullo, IJ, Peissig, PL, McCarty, CA, Bottinger, EP, Gottesman, O, Crosslin, DR, Carrell, DS, Rasmussen-Torvik, LJ, Pacheco, JA, Huang, J, Timpson, NJ, Kettunen, J, Ala-Korpela, M, Mitchell, GF, Parsa, A, Wilkinson, IB, Gorski, M, Li, Yunlei, Franceschini, N, Keller, MF, Ganesh, SK, Langefeld, CD, Bruijn, L, Brown, MA, Evans, DM, Baltic, S, Ferreira, MA, Baurecht, H, Weidinger, S, Franke, A, Lubitz, SA, Muller-Nurasyid, M, Felix, Janine, Smith, NL, Sudman, M, Thompson, SD, Zeggini, E, Panoutsopoulou, K, Nalls, MA, Singleton, A, Polychronakos, C, Bradfield, JP, Hakonarson, H, Easton, DF, Thompson, D, Tomlinson, IP, Dunlop, M, Hemminki, K, Morgan, G, Eisen, T, Goldschmidt, H, Allan, JM, Henrion, M, Whiffin, N, Wang, YF, Chubb, D, Houlston, RS, Iles, MM, Bishop, DT, Law, MH, Hayward, NK, Luo, Y, Nejentsev, S, Barbalic, M, Crossman, D, Sanna, S, Soranzo, N, Markus, HS, Wareham, NJ, Rader, DJ, O Reilly, M, Assimes, T, Harris, TB, Hofman, Bert, Franco Duran, OH, Gudnason, V, Tracy, R, Psaty, BM, Farrall, M, Watkins, H, Hall, AS, Samani, NJ, Marz, W, Clarke, R, Collins, R, Kooner, JS, Chambers, JC, Kathiresan, S, McPherson, R, Erdmann, J, Kastrati, A, Schunkert, H, Stefansson, K, Thorsteinsdottir, U, Walston, JD, Tybjaerg-Hansen, A, Alam, DS, Majumder, AA, Di Angelantonio, E, Chowdhury, R, Nordestgaard, BG, Saleheen, D, Thompson, SG, and Danesh, J
Abstract: Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1 alpha and IL-1 beta); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0.22 SD (95% CI 0.18-0.25; 12.5%; p=9.3 x 10(-33)), concentrations of interleukin 6 decreased by 0.02 SD (-0.04 to -0.01; -1,7%; p=3.5 x 10(-3)), and concentrations of C-reactive protein decreased by 0.03 SD (-0.04 to -0.02; -3.4%; p=7.7 x 10(-14)). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1.15 (1.08-1.22; p=1.8 x 10(-6)) compared with people who ca
Published: 2015

43. Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation

Author: Horikoshi, M, Magi, R, van de Bunt, M, Surakka, I, Sarin, AP, Mahajan, A, Marullo, L, Thorleifsson, G, Hagg, S, Hottenga, JJ (Jouke Jan), Ladenvall, C, Ried, JS, Winkler, TW, Willems, SM, Pervjakova, N, Esko, T, Beekman, M, Nelson, CP, Willenborg, C, Wiltshire, S, Ferreira, T, Fernandez, J, Gaulton, KJ, Steinthorsdottir, V, Hamsten, A, Magnusson, PKE, Willemsen, G, Milaneschi, Y, Robertson, NR, Groves, CJ, Bennett, AJ, Lehtimaki, T, Viikari, JS, Rung, J, Lyssenko, V, Perola, M, Heid, IM, Herder, Cindy, Grallert, H, Muller-Nurasyid, M, Roden, M, Hypponen, E, Isaacs, Aaron, Leeuwen, Elisa, Karssen, Lennart, Mihailov, E, Houwing-Duistermaat, JJ, de Craen, AJM, Deelen, J, Havulinna, AS, Blades, M, Hengstenberg, C, Erdmann, J, Schunkert, H, Kaprio, J, Tobin, MD, Samani, NJ, Lind, L, Salomaa, V, Lindgren, CM, Slagboom, PE (Eline), Metspalu, A, Duijn, Cornelia, Eriksson, JG, Peters, A, Gieger, C, Jula, A, Groop, L, Raitakari, OT, Power, C, Penninx, BWJH, de Geus, ED, Smit, JH, Boomsma, DI, Pedersen, NL, Ingelsson, E, Thorsteinsdottir, U, Stefansson, K, Ripatti, S, Prokopenko, I, McCarthy, MI, Morris, AP, Horikoshi, M, Magi, R, van de Bunt, M, Surakka, I, Sarin, AP, Mahajan, A, Marullo, L, Thorleifsson, G, Hagg, S, Hottenga, JJ (Jouke Jan), Ladenvall, C, Ried, JS, Winkler, TW, Willems, SM, Pervjakova, N, Esko, T, Beekman, M, Nelson, CP, Willenborg, C, Wiltshire, S, Ferreira, T, Fernandez, J, Gaulton, KJ, Steinthorsdottir, V, Hamsten, A, Magnusson, PKE, Willemsen, G, Milaneschi, Y, Robertson, NR, Groves, CJ, Bennett, AJ, Lehtimaki, T, Viikari, JS, Rung, J, Lyssenko, V, Perola, M, Heid, IM, Herder, Cindy, Grallert, H, Muller-Nurasyid, M, Roden, M, Hypponen, E, Isaacs, Aaron, Leeuwen, Elisa, Karssen, Lennart, Mihailov, E, Houwing-Duistermaat, JJ, de Craen, AJM, Deelen, J, Havulinna, AS, Blades, M, Hengstenberg, C, Erdmann, J, Schunkert, H, Kaprio, J, Tobin, MD, Samani, NJ, Lind, L, Salomaa, V, Lindgren, CM, Slagboom, PE (Eline), Metspalu, A, Duijn, Cornelia, Eriksson, JG, Peters, A, Gieger, C, Jula, A, Groop, L, Raitakari, OT, Power, C, Penninx, BWJH, de Geus, ED, Smit, JH, Boomsma, DI, Pedersen, NL, Ingelsson, E, Thorsteinsdottir, U, Stefansson, K, Ripatti, S, Prokopenko, I, McCarthy, MI, and Morris, AP
Abstract: Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency >= 0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
Published: 2015

44. Genetically determined height and coronary artery disease

Author: Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, Kooner,JS, Nelson, C, Hamby, S, Saleheen, D, Hopewell, J, Zeng, L, Assimes, T, Kanoni, S, Willenborg, C, Burgess, S, Amouyel, P, Anand, S, Blankenberg, S, Boehm, B, Clarke, R, Collins, R, Dedoussis, G, Farrall, M, Franks, P, Groop, L, Hall, A, Hamsten, A, Hengstenberg, C, Hovingh, G, Ingelsson, E, Kathiresan, S, Kee, F, König, I, Kooner, J, Lehtimäki, T, März, W, Mcpherson, R, Metspalu, A, Nieminen, M, O'Donnell, C, Palmer, C, Peters, A, Perola, M, Reilly, M, Ripatti, S, Roberts, R, Salomaa, V, Shah, S, Schreiber, S, Siegbahn, A, Thorsteinsdottir, U, Veronesi, G, Wareham, N, Willer, C, Zalloua, P, Erdmann, J, Deloukas, P, Watkins, H, Schunkert, H, Danesh, J, Thompson, J, Samani, N, Goldstein, B, Stirrups, K, Cazier, J, Johansson, Å, Lee, J, Chambers, J, Esko, T, Folkersen, L, Goel, A, Grundberg, E, Havulinna, A, Ho, W, Eriksson, N, Kleber, M, Kristiansson, K, Lundmark, P, Lyytikäinen, L, Rafelt, S, Shungin, D, Strawbridge, R, Thorleifsson, G, Tikkanen, E, Van, Z, N, Voight, B, Waite, L, Zhang, W, Ziegler, A, Absher, D, Altshuler, D, Balmforth, A, Barroso, I, Braund, P, Burgdorf, C, Claudi Boehm, S, Cox, D, Dimitriou, M, Do, R, Doney, A, El, M, Eriksson, P, Fischer, K, Fontanillas, P, Franco Cereceda, A, Gigante, B, Gustafsson, S, Hager, J, Hallmans, G, Han, B, Hunt, S, Kang, H, Illig, T, Kessler, T, Knowles, J, Kolovou, G, Kuusisto, J, Langenberg, C, Langford, C, Leander, K, Lokki, M, Lundmark, A, Mccarthy, M, Meisinger, C, Melander, O, Mihailov, E, Maouche, S, Morris, A, Müller Nurasyid, M, Nikus, K, Peden, J, Rayner, N, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schäfer, A, Sivananthan, M, Song, C, Stewart, A, Tan, S, Thorgeirsson, G, Van, D, Schoot, C, Wagner, P, Wells, G, Wild, P, Yang, T, Arveiler, D, Basart, H, Boehnke, M, Boerwinkle, E, Brambilla, P, Cambien, F, Cupples, A, De, F, U, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Ferrières, J, Gauguier, D, Go, A, Goodall, A, Gudnason, V, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kähönen, M, Kim, H, Klopp, N, Koenig, W, Kratzer, W, Kuulasmaa, K, Laakso, M, Laaksonen, R, Lind, L, Ouwehand, W, Parish, S, Park, J, Pedersen, N, Quertermous, T, Rader, D, Schadt, E, Sinisalo, J, Stark, K, Stefansson, K, Trégouët, D, Virtamo, J, Wallentin, L, Zimmermann, M, Sandhu, M, Pastinen, T, Syvänen, A, Nelson,CP, Hamby,SE, Saleheen,D, Hopewell,JC, Zeng,L, Assimes,TL, Kanoni,S, Willenborg,C, Burgess,S, Amouyel,P, Anand,S, Blankenberg,S, Boehm,BO, Clarke,RJ, Collins,R, Dedoussis,G, Farrall,M, Franks,PW, Groop,L, Hall,AS, Hamsten,A, Hengstenberg,C, Hovingh,GK, Ingelsson,E, Kathiresan,S, Kee,F, König,IR, Kooner,J, Lehtimäki,T, März,W, McPherson,R, Metspalu,A, Nieminen,MS, O'Donnell,CJ, Palmer,CN, Peters,A, Perola,M, Reilly,MP, Ripatti,S, Roberts,R, Salomaa,V, Shah,SH, Schreiber,S, Siegbahn,A, Thorsteinsdottir,U, Veronesi,G, Wareham,N, Willer,CJ, Zalloua,PA, Erdmann,J, Deloukas,P, Watkins,H, Schunkert,H, Danesh,J, Thompson,JR, Samani,NJ, Assimes,T, Goldstein,BA, Stirrups,K, Cazier,JB, Johansson,Å, Lee,JY, Chambers,JC, Esko,T, Folkersen,L, Goel,A, Grundberg,E, Havulinna,AS, Ho,WK, Eriksson,N, Kleber,ME, Kristiansson,K, Lundmark,P, Lyytikäinen,LP, Rafelt,S, Shungin,D, Strawbridge,RJ, Thorleifsson,G, Tikkanen,E, Van, Zuydam, Voight,BF, Waite,LL, Zhang,W, Ziegler,A, Absher,D, Altshuler,D, Balmforth,AJ, Barroso,I, Braund,PS, Burgdorf,C, Claudi Boehm,S, Cox,D, Dimitriou,M, Do,R, Doney,AS, El, Mokhtari, Eriksson,P, Fischer,K, Fontanillas,P, Franco Cereceda,A, Gigante,B, Gustafsson,S, Hager,J, Hallmans,G, Han,BG, Hunt,SE, Kang,HM, Illig,T, Kessler,T, Knowles,JW, Kolovou,G, Kuusisto,J, Langenberg,C, Langford,C, Leander,K, Lokki,ML, Lundmark,A, McCarthy,MI, Meisinger,C, Melander,O, Mihailov,E, Maouche,S, Morris,AD, Müller Nurasyid,M, Nikus,K, Peden,JF, Rayner,NW, Rasheed,A, Rosinger,S, Rubin,D, Rumpf,MP, Schäfer,A, Sivananthan,M, Song,C, Stewart,AF, Tan,ST, Thorgeirsson,G, van, der, Schoot, CE, Wagner,PJ, Wells,GA, Wild,PS, Yang,TP, Arveiler,D, Basart,H, Boehnke,M, Boerwinkle,E, BRAMBILLA, PAOLO, Cambien,F, Cupples,AL, de, Faire, Dehghan,A, Diemert,P, Epstein,SE, Evans,A, Ferrario,MM, Ferrières,J, Gauguier,D, Go,AS, Goodall,AH, Gudnason,V, Hazen,SL, Holm,H, Iribarren,C, Jang,Y, Kähönen,M, Kim,HS, Klopp,N, Koenig,W, Kratzer,W, Kuulasmaa,K, Laakso,M, Laaksonen,R, Lind,L, Ouwehand,WH, Parish,S, Park,JE, Pedersen,NL, Quertermous,T, Rader,DJ, Schadt,E, Sinisalo,J, Stark,K, Stefansson,K, Trégouët,DA, Virtamo,J, Wallentin,L, Zimmermann,ME, Sandhu,MS, Pastinen,T, Syvänen,AC, Blankenberg,SS, Clarke,R, O'Donnell,C, and Kooner,JS
Abstract: BACKGROUND: The nature and underlying mechanisms of an inverse association between adult height and the risk of coronary artery disease (CAD) are unclear. METHODS: We used a genetic approach to investigate the association between height and CAD, using 180 height-associated genetic variants. We tested the association between a change in genetically determined height of 1 SD (6.5 cm) with the risk of CAD in 65,066 cases and 128,383 controls. Using individual-level genotype data from 18,249 persons, we also examined the risk of CAD associated with the presence of various numbers of height-associated alleles. To identify putative mechanisms, we analyzed whether genetically determined height was associated with known cardiovascular risk factors and performed a pathway analysis of the height-associated genes. RESULTS: We observed a relative increase of 13.5% (95% confidence interval [CI], 5.4 to 22.1; P<0.001) in the risk of CAD per 1-SD decrease in genetically determined height. There was a graded relationship between the presence of an increased number of height-raising variants and a reduced risk of CAD (odds ratio for height quartile 4 versus quartile 1, 0.74; 95% CI, 0.68 to 0.84; P<0.001). Of the 12 risk factors that we studied, we observed significant associations only with levels of low-density lipoprotein cholesterol and triglycerides (accounting for approximately 30% of the association). We identified several overlapping pathways involving genes associated with both development and atherosclerosis. CONCLUSIONS: There is a primary association between a genetically determined shorter height and an increased risk of CAD, a link that is partly explained by the association between shorter height and an adverse lipid profile. Shared biologic processes that determine achieved height and the development of atherosclerosis may explain some of the association. (Funded by the British Heart Foundation and others.)
Published: 2015

45. The Relation of Rapid Changes in Obesity Measures to Lipid Profile - Insights from a Nationwide Metabolic Health Survey in 444 Polish Cities

Author: Uversky, VN, Kaess, BM, Jozwiak, J, Nelson, CP, Lukas, W, Mastej, M, Windak, A, Tomasik, T, Grzeszczak, W, Tykarski, A, Gasowski, J, Slezak-Prochazka, I, Slezak, A, Charchar, FJ, Sattar, N, Thompson, JR, Samani, NJ, Tomaszewski, M, Uversky, VN, Kaess, BM, Jozwiak, J, Nelson, CP, Lukas, W, Mastej, M, Windak, A, Tomasik, T, Grzeszczak, W, Tykarski, A, Gasowski, J, Slezak-Prochazka, I, Slezak, A, Charchar, FJ, Sattar, N, Thompson, JR, Samani, NJ, and Tomaszewski, M
Abstract: OBJECTIVE: The impact of fast changes in obesity indices on other measures of metabolic health is poorly defined in the general population. Using the Polish accession to the European Union as a model of political and social transformation we examined how an expected rapid increase in body mass index (BMI) and waist circumference relates to changes in lipid profile, both at the population and personal level. METHODS: Through primary care centres in 444 Polish cities, two cross-sectional nationwide population-based surveys (LIPIDOGRAM 2004 and LIPIDOGRAM 2006) examined 15,404 and 15,453 adult individuals in 2004 and 2006, respectively. A separate prospective sample of 1,840 individuals recruited in 2004 had a follow-up in 2006 (LIPIDOGRAM PLUS). RESULTS: Two years after Polish accession to European Union, mean population BMI and waist circumference increased by 0.6% and 0.9%, respectively. This tracked with a 7.6% drop in HDL-cholesterol and a 2.1% increase in triglycerides (all p<0.001) nationwide. The direction and magnitude of the population changes were replicated at the personal level in LIPIDOGRAM PLUS (0.7%, 0.3%, 8.6% and 1.8%, respectively). However, increases in BMI and waist circumference were both only weakly associated with HDL-cholesterol and triglycerides changes prospectively. The relation of BMI to the magnitude of change in both lipid fractions was comparable to that of waist circumference. CONCLUSIONS: Moderate changes in obesity measures tracked with a significant deterioration in measures of pro-atherogenic dyslipidaemia at both personal and population level. These associations were predominantly driven by factors not measureable directly through either BMI or waist circumference.
Published: 2014

46. Telomere length in circulating leukocytes is associated with lung function and disease

Author: Albrecht, E, Sillanpaa, E, Karrasch, S, Alves, AC, Codd, V, Hovatta, I, Buxton, JL, Nelson, CP, Broer, Linda, Hagg, S, Mangino, M, Willemsen, G, Surakka, I, Ferreira, MAR, Amin, Najaf, Oostra, Ben, Backmand, HM, Peltonen, M, Sarna, S, Rantanen, T, Sipila, S, Korhonen, T, Madden, PAF, Gieger, C, Jorres, RA, Heinrich, J (Joachim), Behr, J, Huber, RM, Peters, A, Strauch, K, Wichmann, HE, Waldenberger, M, Blakemore, AIF, de Geus, EJC, Nyholt, DR, Henders, AK, Piirila, PL, Rissanen, A, Magnusson, PKE, Vinuela, A, Pietilainen, KH, Martin, NG, Pedersen, NL, Boomsma, DI, Spector, TD, Duijn, Cornelia, Kaprio, J, Samani, NJ, Jarvelin, MR, Schulz, H, Albrecht, E, Sillanpaa, E, Karrasch, S, Alves, AC, Codd, V, Hovatta, I, Buxton, JL, Nelson, CP, Broer, Linda, Hagg, S, Mangino, M, Willemsen, G, Surakka, I, Ferreira, MAR, Amin, Najaf, Oostra, Ben, Backmand, HM, Peltonen, M, Sarna, S, Rantanen, T, Sipila, S, Korhonen, T, Madden, PAF, Gieger, C, Jorres, RA, Heinrich, J (Joachim), Behr, J, Huber, RM, Peters, A, Strauch, K, Wichmann, HE, Waldenberger, M, Blakemore, AIF, de Geus, EJC, Nyholt, DR, Henders, AK, Piirila, PL, Rissanen, A, Magnusson, PKE, Vinuela, A, Pietilainen, KH, Martin, NG, Pedersen, NL, Boomsma, DI, Spector, TD, Duijn, Cornelia, Kaprio, J, Samani, NJ, Jarvelin, MR, and Schulz, H
Abstract: Several clinical studies suggest the involvement of premature ageing processes in chronic obstructive pulmonary disease (COPD). Using an epidemiological approach, we studied whether accelerated ageing indicated by telomere length, a marker of biological age, is associated with COPD and asthma, and whether intrinsic age-related processes contribute to the interindividual variability of lung function. Our meta-analysis of 14 studies included 934 COPD cases with 15 846 controls defined according to the Global Lungs Initiative (GLI) criteria (or 1189 COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria), 2834 asthma cases with 28 195 controls, and spirometric parameters (forced expiratory volume in is (FEV1), forced vital capacity (PVC) and FEV1/FVC) of 12 595 individuals. Associations with telomere length were tested by linear regression, adjusting for age, sex and smoking status. We observed negative associations between telomere length and asthma (beta= -0.0452, p= 0.024) as well as COPD (beta= -0.0982, p=0.001), with associations being stronger and more significant when using GLI criteria than those of GOLD. In both diseases, effects were stronger in females than males. The investigation of spirometric indices showed positive associations between telomere length and FEV1 (p=1.07 x 10(-7)), FVC (p=2.07 x 10(-5)), and FEV1/FVC (p =5.27 x 10(-3)). The effect was somewhat weaker in apparently healthy subjects than in COPD or asthma patients. Our results provide indirect evidence for the hypothesis that cellular senescence may contribute to the pathogenesis of COPD and asthma, and that lung function may reflect biological ageing primarily due to intrinsic processes, which are likely to be aggravated in lung diseases.
Published: 2014

47. The role of adiposity in cardiometabolic traits: a mendelian randomization analysis

Author: Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, Prokopenko, I., Fall, T, Hägg, S, Mägi, R, Ploner, A, Fischer, K, Horikoshi, M, Sarin, A, Thorleifsson, G, Ladenvall, C, Kals, M, Kuningas, M, Draisma, H, Ried, J, Van, Z, Nr, Huikari, V, Mangino, M, Sonestedt, E, Benyamin, B, Nelson, C, Rivera, N, Kristiansson, K, Shen, H, Havulinna, A, Dehghan, A, Donnelly, L, Kaakinen, M, Nuotio, M, Robertson, N, de Bruijn, R, Ikram, M, Amin, N, Balmforth, A, Braund, P, Doney, A, Döring, A, Elliott, P, Esko, T, Franco, O, Gretarsdottir, S, Hartikainen, A, Heikkilä, K, Herzig, K, Holm, H, Hottenga, J, Hyppönen, E, Illig, T, Isaacs, A, Isomaa, B, Karssen, L, Kettunen, J, Koenig, W, Kuulasmaa, K, Laatikainen, T, Laitinen, J, Lindgren, C, Lyssenko, V, Läärä, E, Rayner, N, Männistö, S, Pouta, A, Rathmann, W, Rivadeneira, F, Ruokonen, A, Savolainen, M, Sijbrands, E, Small, K, Smit, J, Steinthorsdottir, V, Syvänen, A, Taanila, A, Tobin, M, Uitterlinden, A, Willems, S, Willemsen, G, Witteman, J, Perola, M, Evans, A, Ferrières, J, Virtamo, J, Kee, F, Tregouet, D, Arveiler, D, Amouyel, P, Ferrario, M, Brambilla, P, Hall, A, Heath, A, Madden, P, Martin, N, Montgomery, G, Whitfield, J, Jula, A, Knekt, P, Oostra, B, van Duijn, C, Penninx, B, Davey Smith, G, Kaprio, J, Samani, N, Gieger, C, Peters, A, Wichmann, H, Boomsma, D, de Geus, E, Tuomi, T, Power, C, Hammond, C, Spector, T, Lind, L, Orho Melander, M, Palmer, C, Morris, A, Groop, L, Järvelin, M, Salomaa, V, Vartiainen, E, Hofman, A, Ripatti, S, Metspalu, A, Thorsteinsdottir, U, Stefansson, K, Pedersen, N, Mccarthy, M, Ingelsson, E, Prokopenko, I, Sarin, AP, Draisma, HH, Ried, JS, van, Zuydam, NR, Nelson, CP, Rivera, NV, Shen, HY, Havulinna, AS, Donnelly, LA, Nuotio, ML, de Bruijn, RF, Ikram, MA, Balmforth, AJ, Braund, PS, Doney, AS, Franco, OH, Hartikainen, AL, Herzig, KH, Hottenga, JJ, Karssen, LC, Rayner, NW, Savolainen, MJ, Sijbrands, EJ, Small, KS, Smit, JH, Syvänen, AC, Tobin, MD, Uitterlinden, AG, Willems, SM, Tregouet, DA, Ferrario, MM, BRAMBILLA, PAOLO, Hall, AS, Heath, AC, Madden, PA, Martin, NG, Montgomery, GW, Whitfield, JB, van Duijn, CM, Penninx, BW, Samani, NJ, Wichmann, HE, Boomsma, DI, de Geus, EJ, Hammond, CJ, Spector, TD, Palmer, CN, Morris, AD, Järvelin, MR, Pedersen, NL, McCarthy, MI, and Prokopenko, I.
Abstract: Background:The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.Methods and Findings:We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses.Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (
Published: 2013

48. Genome-Wide Association Study Identifies Novel Loci Associated with Circulating Phospho- and Sphingolipid Concentrations

Author: Demirkan, Ayse, Duijn, Cornelia, Ugocsai, P, Isaacs, Aaron, Pramstaller, PP, Liebisch, G, Wilson, JF, Johansson, A, Rudan, I, Aulchenko, YS, Kirichenko, AV, Janssens, Cecile, Jansen, RC, Gnewuch, C, Domingues, FS, Pattaro, C, Wild, SH, Jonasson, I, Polasek, O, Zorkoltseva, IV, Hofman, Bert, Karssen, Lennart, Struchalin, M, Floyd, J, Igl, W, Biloglav, Z, Broer, Linda, Pfeufer, A, Pichler, I, Campbell, S, Zaboli, G, Kolcic, I, Rivadeneira, Fernando, Huffman, J, Hastie, ND, Uitterlinden, André, Franke, L, Franklin, CS, Vitart, V, Nelson, CP, Preuss, M, Bis, JC, O'Donnell, CJ, Franceschini, N, Witteman, JCM, Axenovich, T, Oostra, Ben, Meitinger, T, Hicks, AA, Hayward, C, Wright, AF, Gyllensten, U, Campbell, H, Schmitz, G, Demirkan, Ayse, Duijn, Cornelia, Ugocsai, P, Isaacs, Aaron, Pramstaller, PP, Liebisch, G, Wilson, JF, Johansson, A, Rudan, I, Aulchenko, YS, Kirichenko, AV, Janssens, Cecile, Jansen, RC, Gnewuch, C, Domingues, FS, Pattaro, C, Wild, SH, Jonasson, I, Polasek, O, Zorkoltseva, IV, Hofman, Bert, Karssen, Lennart, Struchalin, M, Floyd, J, Igl, W, Biloglav, Z, Broer, Linda, Pfeufer, A, Pichler, I, Campbell, S, Zaboli, G, Kolcic, I, Rivadeneira, Fernando, Huffman, J, Hastie, ND, Uitterlinden, André, Franke, L, Franklin, CS, Vitart, V, Nelson, CP, Preuss, M, Bis, JC, O'Donnell, CJ, Franceschini, N, Witteman, JCM, Axenovich, T, Oostra, Ben, Meitinger, T, Hicks, AA, Hayward, C, Wright, AF, Gyllensten, U, Campbell, H, and Schmitz, G
Abstract: Phospho- and sphingolipids are crucial cellular and intracellular compounds. These lipids are required for active transport, a number of enzymatic processes, membrane formation, and cell signalling. Disruption of their metabolism leads to several diseases, with diverse neurological, psychiatric, and metabolic consequences. A large number of phospholipid and sphingolipid species can be detected and measured in human plasma. We conducted a meta-analysis of five European family-based genome-wide association studies (N = 4034) on plasma levels of 24 sphingomyelins (SPM), 9 ceramides (CER), 57 phosphatidylcholines (PC), 20 lysophosphatidylcholines (LPC), 27 phosphatidylethanolamines (PE), and 16 PE-based plasmalogens (PLPE), as well as their proportions in each major class. This effort yielded 25 genome-wide significant loci for phospholipids (smallest P-value = 9.88 x 10(-204)) and 10 loci for sphingolipids (smallest P-value = 3.10 x 10(-57)). After a correction for multiple comparisons (P-value, 2.2 x 10(-9)), we observed four novel loci significantly associated with phospholipids (PAQR9, AGPAT1, PKD2L1, PDXDC1) and two with sphingolipids (PLD2 and APOE) explaining up to 3.1% of the variance. Further analysis of the top findings with respect to within class molar proportions uncovered three additional loci for phospholipids (PNLIPRP2, PCDH20, and ABDH3) suggesting their involvement in either fatty acid elongation/saturation processes or fatty acid specific turnover mechanisms. Among those, 14 loci (KCNH7, AGPAT1, PNLIPRP2, SYT9, FADS1-2-3, DLG2, APOA1, ELOVL2, CDK17, LIPC, PDXDC1, PLD2, LASS4, and APOE) mapped into the glycerophospholipid and 12 loci (ILKAP, ITGA9, AGPAT1, FADS1-2-3, APOA1, PCDH20, LIPC, PDXDC1, SGPP1, APOE, LASS4, and PLD2) to the sphingolipid pathways. In large meta-analyses, associations between FADS1-2-3 and carotid intima media thickness, AGPAT1 and type 2 diabetes, and APOA1 and coronary artery disease were observed. In conclusion, our study iden
Published: 2012

49. Rationale and design issues of the randomized intervention for children with vesicoureteral reflux (RIVUR) study

Author: Keren, R, Carpenter, MA, Hoberman, A, Shaikh, N, Matoo, TK, Chesney, RW, Matthews, R, Gerson, AC, Greenfield, SP, Fivush, B, McLurie, GA, Rushton, HG, Canning, D, Nelson, CP, Greenbaum, L, Bukowski, T, Primack, W, Sutherland, R, Hosking, J, Stewart, D, Elder, J, Moxey-Mims, M, Nyberg, L, Keren, R, Carpenter, MA, Hoberman, A, Shaikh, N, Matoo, TK, Chesney, RW, Matthews, R, Gerson, AC, Greenfield, SP, Fivush, B, McLurie, GA, Rushton, HG, Canning, D, Nelson, CP, Greenbaum, L, Bukowski, T, Primack, W, Sutherland, R, Hosking, J, Stewart, D, Elder, J, Moxey-Mims, M, and Nyberg, L
Abstract: OBJECTIVE. Our goal is to determine if antimicrobial prophylaxis with trimethoprim/sulfamethoxazole prevents recurrent urinary tract infections and renal scarring in children who are found to have vesicoureteral reflux after a first or second urinary tract infection. DESIGN, PARTICIPANTS, AND METHODS. The Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) study is a double-blind, randomized, placebo-controlled trial. Six hundred children aged 2 to 72 months will be recruited from both primary and subspecialty care settings at clinical trial centers throughout North America. Children who are found to have grades I to IV vesicoureteral reflux after the index febrile or symptomatic urinary tract infection will be randomly assigned to receive daily doses of either trimethoprim/sulfamethoxazole or placebo for 2 years. Scheduled follow-up contacts include in-person study visits every 6 months and telephone interviews every 2 months. Biospecimens (urine and blood) and genetic specimens (blood) will be collected for future studies of the genetic and biochemical determinants of vesicoureteral reflux, recurrent urinary tract infection, renal insufficiency, and renal scarring. RESULTS. The primary outcome is recurrence of urinary tract infection. Secondary outcomes include time to recurrent urinary tract infection, renal scarring (assessed by dimercaptosuccinic acid scan), treatment failure, renal function, resource utilization, and development of antimicrobial resistance in stool flora. CONCLUSIONS. The RIVUR study will provide useful information to clinicians about the risks and benefits of prophylactic antibiotics for children who are diagnosed with vesicoureteral reflux after a first or second urinary tract infection. The data and specimens collected over the course of the study will allow researchers to better understand the pathophysiology of recurrent urinary tract infection and its sequelae. Copyright © 2008 by the American Academy of Pediatrics.
Published: 2008

50. EUTUBS: A Mnemonic for the complete endoscopic examination of the lower urinary tract

Author: Olapade-Olaopa, EO, primary, Nelson, CP, additional, Adebayo, SA, additional, Fakolujo, AD, additional, and Bloom, DA, additional
Published: 2004
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