Author: "Doney, A.S.F." - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Doney, A.S.F."' showing total 33 results

Start Over Author "Doney, A.S.F."

33 results on '"Doney, A.S.F."'

1. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

Author: Aziz, J., Dobson, G., Doney, A.S.F., Flynn, R.W.V., Furnace, J., Grieve, J.W.K., Guthrie, G., Jamieson, D., Jennings, C.G., Kean, S., Lund, L.C., McConnachie, A., Pigazzani, F., Riches, P.L., Rix Hanson, M., Rogers, A, Rooke, E.D.M., Thomson, J., Warren, M., Wetherall, K., Wilson, R., Hall, C.P., Maseri, A., Bird, H.A., Murray, G., Dear, J.W., Petrie, M., MacDonald, M., Jhund, P.S., Connolly, E., Murphy, D.J., Paul, N., Olsson, A., Koskinen, P.T., Fuat, A., Foster, A., Saywood, W., Barr, R.J., McConnachie, L., Wilson, L.F., Larsen Rasmussen, L., McGinnis, A.R., Birrell, H., Keiller, M., Bremner, I.S., Forbes, G.J., Dumbleton, J.S., Rhodes, J., Waller, T., Mackenzie, Isla S, Ford, Ian, Nuki, George, Hallas, Jesper, Hawkey, Christopher J, Webster, John, Ralston, Stuart H, Walters, Matthew, Robertson, Michele, De Caterina, Raffaele, Findlay, Evelyn, Perez-Ruiz, Fernando, McMurray, John J V, and MacDonald, Thomas M
Published: 2020
Full Text: View/download PDF

2. The cost of cerebral ischaemia

Author: Flynn, R.W.V., MacWalter, R.S.M., and Doney, A.S.F.
Published: 2008
Full Text: View/download PDF

3. Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (Nature Communications, (2021), 12, 1, (24), 10.1038/s41467-020-19366-9)

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J.L. (Josine L.), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A.J. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), Geus, E.J.C. (Eco) de, Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), Duijn, C.M. (Cornelia) van, Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Matullo, G., Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth J. F.), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P. (Patricia), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Barroso, I.E. (Inês), Morris, A.P. (Andrew), and Prokopenko, I. (Inga)
Abstract: The original version of this Article contained an error in Fig. 2, in which panels a and b were inadvertently swapped. This has now been corrected in the PDF and HTML versions of the Article.
Published: 2021
Full Text: View/download PDF

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

Author: Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), Prokopenko, I. (Inga), Lagou, V. (Vasiliki), Mägi, R. (Reedik), Hottenga, J.J. (Jouke Jan), Grallert, H. (Harald), Perry, J.R.B. (John R. B.), Bouatia-Naji, N. (Nabila), Marullo, L. (Letizia), Rybin, D. (Denis), Jansen, R. (Rick), Min, J. (Josine), Dimas, A.S. (Antigone), Ulrich, A. (Anna), Zudina, L. (Liudmila), Gådin, J.R. (Jesper R.), Jiang, L. (Longda), Faggian, A. (Alessia), Bonnefond, A. (Amélie), Fadista, J. (João), Stathopoulou, M.G. (Maria G), Isaacs, A. (Aaron), Willems, S.M. (Sara), Navarro, P. (Pau), Tanaka, T. (Toshiko), Jackson, A.U. (Anne U.), Montasser, M.E. (May E.), O’Connell, J.R. (Jeff R.), Bielak, L.F. (Lawrence F.), Webster, R.J. (Rebecca J.), Meitinger, T. (Thomas), Stafford, M., Pourcain, B.S. (Beate St), Timpson, N.J. (Nicholas J.), Salo, P. (Perttu), Shin, S.-Y., Amin, N. (Najaf), Smith, A.V. (Albert), Li, G. (Guo), Verweij, N. (Niek), Goel, A. (Anuj), Ford, I. (Ian), Johnson, P.C.D. (Paul C. D.), Johnson, T. (Toby), Kapur, K. (Karen), Thorleifsson, G. (Gudmar), Strawbridge, R.J. (Rona), Rasmussen-Torvik, L.J. (Laura), Esko, T. (Tõnu), Mihailov, E. (Evelin), Fall, T. (Tove), Fraser, R.M. (Ross), Mahajan, A. (Anubha), Kanoni, S. (Stavroula), Giedraitis, V. (Vilmantas), Kleber, M.E. (Marcus E.), Silbernagel, G. (Günther), Meyer, J. (Julia), Müller-Nurasyid, M. (Martina), Ganna, A. (Andrea), Sarin, A.-P., Yengo, L. (Loic), Shungin, D. (Dmitry), Luan, J. (Jian’an), Horikoshi, M. (Momoko), An, P. (Ping), Sanna, S. (Serena), Boettcher, Y. (Yvonne), Rayner, N.W. (Nigel William), Nolte, I.M. (Ilja), Zemunik, T. (Tatijana), Iperen, E. (Erik van), Kovacs, P. (Peter), Hastie, N. (Nick), Wild, S.H. (Sarah H.), McLachlan, S. (Stela), Campbell, S. (Susan), Polasek, O. (Ozren), Carlson, O.D. (Olga), Egan, J. (Josephine), Kieß, W. (Wieland), Willemsen, G. (Gonneke), Kuusisto, J. (Johanna), Laakso, M. (Markku), Dimitriou, M. (Maria), Hicks, A.A. (Andrew A.), Rauramaa, R. (Rainer), Bandinelli, S. (Stefania), Thorand, B. (Barbara), Liu, Y. (Yongmei), Miljkovic, I. (Iva), Kao, W.H.L. (Wen), Doney, A.S.F. (Alex), Perola, M. (Markus), Hingorani, A. (Aroon), Kivimaki, M. (Mika), Kumari, M. (Meena), Bennett, A.J. (Amanda J.), Groves, C.J. (Christopher J.), Herder, C. (Christian), Koistinen, H.A. (Heikki A.), Kinnunen, L. (Leena), Faire, U.D. (Ulf), Bakker, S.J.L. (Stephan), Uusitupa, M. (Matti), Palmer, C.N.A. (Colin N. A.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Pouta, A. (Anneli), Snieder, H. (Harold), Boerwinkle, E.A. (Eric), Palmer, C.N.A. (Colin), Magnusson, P.K. (Patrik), Krus, U. (Ulrika), Scapoli, C. (Chiara), de Geus, E.J.C.N. (Eco J. C. N.), Blüher, M. (Matthias), Wolffenbuttel, B.H.R. (Bruce), Province, M.A. (Michael A.), Abecasis, G.R. (Goncalo R.), Meigs, J.B. (James B.), Hovingh, G.K. (G. Kees), Lindström, J. (Jaana), Wilson, J.F. (James F.), Wright, A.F. (Alan F.), Dedoussis, G.V. (George), Bornstein, S.R. (Stefan), Schwarz, P.E.H. (Peter), Tönjes, A. (Anke), Winkelmann, B., Boehm, B.O. (Bernhard O.), März, W. (Winfried), Metspalu, A. (Andres), Price, J.F. (Jackie F.), Deloukas, P. (Panos), Körner, A. (Antje), Lakka, T.A. (Timo), Keinanen-Kiukaanniemi, S. (Sirkka), Saaristo, T. (Timo), Bergman, R.N. (Richard N.), Tuomilehto, J. (Jaakko), Wareham, N.J. (Nick), Langenberg, C. (Claudia), Männistö, S. (Satu), Franks, P.W. (Paul W.), Hayward, C. (Caroline), Vitart, V. (Veronique), Kaprio, J. (Jaakko), Visvikis-Siest, S. (Sophie), Balkau, B. (Beverley), Altshuler, D. (David), Rudan, I. (Igor), Stumvoll, M. (Michael), Campbell, H. (Harry), van Duijn, C.M. (Cornelia M.), Gieger, C. (Christian), Illig, T. (Thomas), Ferrucci, L. (Luigi), Pedersen, N.L. (Nancy L.), Pramstaller, P.P. (Peter Paul), Boehnke, M. (Michael), Frayling, T.M. (Timothy M.), Shuldiner, A.R. (Alan R.), Peyser, P.A. (Patricia A.), Kardia, S.L.R. (Sharon L. R.), Palmer, L.J. (Lyle J.), Penninx, B.W.J.H. (Brenda), Meneton, P. (Pierre), Harris, T.B. (Tamara), Navis, G. (Gerjan), Harst, P. (Pim van der), Smith, G.D. (George Davey), Forouhi, N.G. (Nita), Loos, R.J.F. (Ruth), Salomaa, V. (Veikko), Soranzo, N. (Nicole), Boomsma, D.I. (Dorret I.), Groop, L. (Leif), Tuomi, T. (Tiinamaija), Hofman, A. (Albert), Munroe, P.B. (Patricia B.), Gudnason, V. (Vilmundur), Siscovick, D.S. (David), Watkins, H. (Hugh), Lecoeur, C. (Cécile), Vollenweider, P. (Peter), Franco-Cereceda, A. (Anders), Eriksson, P. (Per), Jarvelin, M.-R. (Marjo-Riitta), Zwart, J-A. (John-Anker), Hamsten, A. (Anders), Nicholson, G. (George), Karpe, F. (Fredrik), Frants, R.R. (Rune), Lindgren, C.M. (Cecilia M.), McCarthy, M.I. (Mark I.), Froguel, P. (Philippe), Kaakinen, M.A. (Marika A.), Lyssenko, V. (Valeriya), Watanabe, R.M. (Richard), Ingelsson, E. (Erik), Sijbrands, E.J.G. (Eric), Dupuis, J. (Josée), Barroso, I.E. (Inês), Morris, A.P. (Andrew P.), and Prokopenko, I. (Inga)
Abstract: Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
Published: 2021
Full Text: View/download PDF

5. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

Author: Mackenzie, Isla S, primary, Ford, Ian, additional, Nuki, George, additional, Hallas, Jesper, additional, Hawkey, Christopher J, additional, Webster, John, additional, Ralston, Stuart H, additional, Walters, Matthew, additional, Robertson, Michele, additional, De Caterina, Raffaele, additional, Findlay, Evelyn, additional, Perez-Ruiz, Fernando, additional, McMurray, John J V, additional, MacDonald, Thomas M, additional, Aziz, J., additional, Dobson, G., additional, Doney, A.S.F., additional, Flynn, R.W.V., additional, Furnace, J., additional, Grieve, J.W.K., additional, Guthrie, G., additional, Jamieson, D., additional, Jennings, C.G., additional, Kean, S., additional, Lund, L.C., additional, McConnachie, A., additional, Pigazzani, F., additional, Riches, P.L., additional, Rix Hanson, M., additional, Rogers, A, additional, Rooke, E.D.M., additional, Thomson, J., additional, Warren, M., additional, Wetherall, K., additional, Wilson, R., additional, Hall, C.P., additional, Maseri, A., additional, Bird, H.A., additional, Murray, G., additional, Dear, J.W., additional, Petrie, M., additional, MacDonald, M., additional, Jhund, P.S., additional, Connolly, E., additional, Murphy, D.J., additional, Paul, N., additional, Olsson, A., additional, Koskinen, P.T., additional, Fuat, A., additional, Foster, A., additional, Saywood, W., additional, Barr, R.J., additional, McConnachie, L., additional, Wilson, L.F., additional, Larsen Rasmussen, L., additional, McGinnis, A.R., additional, Birrell, H., additional, Keiller, M., additional, Bremner, I.S., additional, Forbes, G.J., additional, Dumbleton, J.S., additional, Rhodes, J., additional, and Waller, T., additional
Published: 2020
Full Text: View/download PDF

6. Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Author: Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), Palmer, C.N.A. (Colin), Van Zuydam, N.R. (Natalie R.), Ladenvall, C. (Claes), Voight, B.F. (Benjamin), Strawbridge, R.J. (Rona), Fernandez-Tajes, J. (Juan), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil R.), Mahajan, A. (Anubha), Vlachopoulou, E. (Efthymia), Goel, A. (Anuj), Kleber, M.E. (Marcus), Nelson, C.P. (Christopher P.), Kwee, L.C. (Lydia Coulter), Esko, T. (Tõnu), Mihailov, E. (Evelin), Mägi, R. (Reedik), Milani, L. (Lili), Fischer, K. (Krista), Kanoni, S. (Stavroula), Kumar, J. (Jitender), Song, C. (Ci), Hartiala, J.A. (Jaana A.), Pedersen, N.L. (Nancy), Perola, M. (Markus), Gieger, C. (Christian), Peters, A. (Annette), Qu, L. (Liming), Willems, S.M. (Sara), Doney, A.S.F. (Alex), Morris, A.D. (Andrew D.), Zheng, Y. (Yan), Sesti, G. (Giorgio), Hu, F.B. (Frank), Qi, L. (Lu), Laakso, M. (Markku), Thorsteinsdottir, U. (Unnur), Grallert, H. (Harald), Duijn, C.M. (Cornelia) van, Reilly, M.P. (Muredach), Ingelsson, E. (Erik), Deloukas, P. (Panos), Kathiresan, S. (Sek), Metspalu, A. (Andres), Shah, S.H. (Svati), Sinisalo, J. (Juha), Salomaa, V. (Veikko), Hamsten, A. (Anders), Samani, N.J. (Nilesh), Ye, S. (Shu), Hazen, S.L. (Stanley), Watkins, H. (Hugh), Saleheen, D. (Danish), Morris, A.P. (Andrew), Colhoun, H.M. (H.), Groop, L. (Leif), McCarthy, M.I. (Mark), and Palmer, C.N.A. (Colin)
Abstract: Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (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 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 characterized 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 with those without T2D.
Published: 2020
Full Text: View/download PDF

7. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Author: Shah, S. (Sonia), Henry, A. (Albert), Roselli, C. (Carolina), Lin, H. (Honghuang), Sveinbjörnsson, G. (Garðar), Fatemifar, G. (Ghazaleh), Hedman, A.K. (Asa), Wilk, J.B. (Jemma), Morley, M.P. (Michael P.), Chaffin, M.D. (Mark D.), Helgadottir, H.T. (Hafdis), Verweij, N. (Niek), Dehghan, A. (Abbas), Almgren, P. (Peter), Andersson, C. (Charlotte), Aragam, K.G. (Krishna G.), Ärnlöv, J. (Johan), Backman, J.D. (Joshua D.), Biggs, M.L. (Mary L.), Bloom, H.L. (Heather L.), Brandimarto, J. (Jeffrey), Brown, M.R. (Michael R.), Buckbinder, L. (Leonard), Carey, D.J. (David J.), Chasman, D.I. (Daniel I.), Chen, X. (Xing), Chen, X. (Xu), Chung, J. (Jonathan), Chutkow, W. (William), Cook, J.P. (James P.), Delgado, G., Denaxas, S. (Spiros), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Dudley, S.C. (Samuel C.), Dunn, M.E. (Michael E.), Engström, G., Esko, T. (Tõnu), Felix, S.B. (Stephan B.), Finan, C. (Chris), Ford, I. (Ian), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Giedraitis, V. (Vilmantas), Giulianini, F. (Franco), Gottdiener, J.S. (John), Gross, S. (Stefan), Guðbjartsson, D.F. (Daníel F.), Gutmann, R. (Rebecca), Haggerty, C.M. (Christopher M.), Harst, P. (Pim) van der, Hyde, C.L. (Craig L.), Ingelsson, E. (Erik), Jukema, J.W. (Jan Wouter), Kavousi, M. (Maryam), Khaw, K.-T. (Kay-Tee), Kleber, M.E. (Marcus), Køber, L. (Lars), Koekemoer, A. (Andrea), Langenberg, C. (Claudia), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), London, B. (Barry), Lotta, L.A. (Luca A.), Lovering, R.C. (Ruth C.), Luan, J., Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), Margulies, K.B. (Kenneth B.), Ye, S. (Shu), Melander, O. (Olle), Mordi, I.R. (Ify R.), Morgan, T. (Thomas), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Morrison, A.C. (Alanna C.), Nagle, M.W. (Michael W.), Nelson, C.P. (Christopher P.), Niessner, A. (Alexander), Niiranen, T. (Teemu), O’Donoghue, M.L. (Michelle L.), Owens, A.T. (Anjali T.), Palmer, C.N.A. (Colin N. A.), Parry, H.M. (Helen M.), Perola, M. (Markus), Portilla-Fernandez, E. (Eliana), Psaty, B.M. (Bruce M.), Abecasis, G. (Goncalo), Backman, J. (Joshua), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Banerjee, N. (Nilanjana), Baras, A. (Aris), Barnard, L. (Leland), Beechert, C. (Christina), Blumenfeld, A. (Andrew), Cantor, M. (Michael), Chai, Y. (Yating), Coppola, G. (Giovanni), Damask, A. (Amy), Dewey, F. (Frederick), Economides, A. (Aris), Eom, G. (Gisu), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Gurski, L. (Lauren), Guzzardo, P.M. (Paloma M.), Habegger, L. (Lukas), Hahn, Y. (Young), Hawes, A. (Alicia), van Hout, C. (Cristopher), Jones, M.B. (Marcus B.), Khalid, S. (Shareef), Lattari, M. (Michael), Li, A. (Alexander), Lin, N. (Nan), Liu, D. (Daren), Lopez, A. (Alexander), Manoochehri, K. (Kia), Marchini, J. (Jonathan), Marcketta, A. (Anthony), Maxwell, E.K. (Evan K.), McCarthy, S. (Shane), Mitnaul, L.J. (Lyndon), O’Dushlaine, C. (Colm), Overton, J.D. (John D.), Padilla, M.S. (Maria Sotiropoulos), Paulding, C. (Charles), Penn, J. (John), Pradhan, M. (Manasi), Reid, J.G. (Jeffrey G.), Schleicher, T.D. (Thomas D.), Schurmann, C. (Claudia), Shuldiner, A. (Alan), Staples, J.C. (Jeffrey C.), Sun, D. (Dylan), Toledo, K. (Karina), Ulloa, R.H. (Ricardo H.), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Yadav, A. (Ashish), Ye, B. (Bin), Rice, K.M. (Kenneth), Ridker, P.M. (Paul M.), Romaine, S.P.R. (Simon P. R.), Rotter, J.I. (Jerome I.), Salo, P. (Perttu), Salomaa, V. (Veikko), Setten, J. (Jessica) van, Shalaby, A.A. (Alaa A.), Smelser, D.T. (Diane T.), Smith, N.L. (Nicholas L.), Stender, S. (Steen), Stott, D.J. (David. J.), Svensson, P. (Per), Tammesoo, M.L., Taylor, K.D. (Kent D.), Teder-Laving, M. (Maris), Teumer, A. (Alexander), Thorgeirsson, G. (Guðmundur), Thorsteinsdottir, U. (Unnur), Torp-Pedersen, C. (Christian Tobias), Trompet, S. (Stella), Tyl, B. (Benoit), Uitterlinden, A.G. (Andre G.), Veluchamy, A. (Abirami), Völker, U. (Uwe), Voors, A.A. (Adriaan A.), Wang, X. (Xiaosong), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weeke, P.E. (Peter E.), Weiss, R. (Ram), Wiggins, K.L. (Kerri L.), Xing, H. (Heming), Yerges-Armstrong, L.M. (Laura), Yu, B. (Bing), Zannad, F. (Faiez), Zhao, J.H. (Jing Hua), Hemingway, H., Samani, N.J. (Nilesh J.), McMurray, J.J.V. (John J. V.), Yang, J. (Jian), Visscher, P.M. (Peter M.), Newton-Cheh, C. (Christopher), Mälarstig, A. (Anders), Holm, H. (Hilma), Lubitz, S.A. (Steven), Sattar, N. (Naveed), Holmes, M.V. (Michael), Cappola, T.P. (Thomas P.), Asselbergs, F.W. (Folkert), Hingorani, A. (Aroon), Kuchenbaecker, K.B. (Karoline), Ellinor, P.T. (Patrick), Lang, C.C. (Chim C.), Stefansson, K. (Kari), Smith, J.G. (J Gustav), Vasan, R.S. (Ramachandran Srini), Swerdlow, D.I. (Daniel), Lumbers, R.T. (R. Thomas), Shah, S. (Sonia), Henry, A. (Albert), Roselli, C. (Carolina), Lin, H. (Honghuang), Sveinbjörnsson, G. (Garðar), Fatemifar, G. (Ghazaleh), Hedman, A.K. (Asa), Wilk, J.B. (Jemma), Morley, M.P. (Michael P.), Chaffin, M.D. (Mark D.), Helgadottir, H.T. (Hafdis), Verweij, N. (Niek), Dehghan, A. (Abbas), Almgren, P. (Peter), Andersson, C. (Charlotte), Aragam, K.G. (Krishna G.), Ärnlöv, J. (Johan), Backman, J.D. (Joshua D.), Biggs, M.L. (Mary L.), Bloom, H.L. (Heather L.), Brandimarto, J. (Jeffrey), Brown, M.R. (Michael R.), Buckbinder, L. (Leonard), Carey, D.J. (David J.), Chasman, D.I. (Daniel I.), Chen, X. (Xing), Chen, X. (Xu), Chung, J. (Jonathan), Chutkow, W. (William), Cook, J.P. (James P.), Delgado, G., Denaxas, S. (Spiros), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Dudley, S.C. (Samuel C.), Dunn, M.E. (Michael E.), Engström, G., Esko, T. (Tõnu), Felix, S.B. (Stephan B.), Finan, C. (Chris), Ford, I. (Ian), Ghanbari, M. (Mohsen), Ghasemi, S. (Sahar), Giedraitis, V. (Vilmantas), Giulianini, F. (Franco), Gottdiener, J.S. (John), Gross, S. (Stefan), Guðbjartsson, D.F. (Daníel F.), Gutmann, R. (Rebecca), Haggerty, C.M. (Christopher M.), Harst, P. (Pim) van der, Hyde, C.L. (Craig L.), Ingelsson, E. (Erik), Jukema, J.W. (Jan Wouter), Kavousi, M. (Maryam), Khaw, K.-T. (Kay-Tee), Kleber, M.E. (Marcus), Køber, L. (Lars), Koekemoer, A. (Andrea), Langenberg, C. (Claudia), Kao, W.H.L. (Wen), Lindgren, C.M. (Cecilia M.), London, B. (Barry), Lotta, L.A. (Luca A.), Lovering, R.C. (Ruth C.), Luan, J., Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), Margulies, K.B. (Kenneth B.), Ye, S. (Shu), Melander, O. (Olle), Mordi, I.R. (Ify R.), Morgan, T. (Thomas), Morris, A.D. (Andrew D.), Morris, A.P. (Andrew), Morrison, A.C. (Alanna C.), Nagle, M.W. (Michael W.), Nelson, C.P. (Christopher P.), Niessner, A. (Alexander), Niiranen, T. (Teemu), O’Donoghue, M.L. (Michelle L.), Owens, A.T. (Anjali T.), Palmer, C.N.A. (Colin N. A.), Parry, H.M. (Helen M.), Perola, M. (Markus), Portilla-Fernandez, E. (Eliana), Psaty, B.M. (Bruce M.), Abecasis, G. (Goncalo), Backman, J. (Joshua), Bai, X. (Xiaodong), Balasubramanian, S. (Suganthi), Banerjee, N. (Nilanjana), Baras, A. (Aris), Barnard, L. (Leland), Beechert, C. (Christina), Blumenfeld, A. (Andrew), Cantor, M. (Michael), Chai, Y. (Yating), Coppola, G. (Giovanni), Damask, A. (Amy), Dewey, F. (Frederick), Economides, A. (Aris), Eom, G. (Gisu), Forsythe, C. (Caitlin), Fuller, E.D. (Erin D.), Gu, Z. (Zhenhua), Gurski, L. (Lauren), Guzzardo, P.M. (Paloma M.), Habegger, L. (Lukas), Hahn, Y. (Young), Hawes, A. (Alicia), van Hout, C. (Cristopher), Jones, M.B. (Marcus B.), Khalid, S. (Shareef), Lattari, M. (Michael), Li, A. (Alexander), Lin, N. (Nan), Liu, D. (Daren), Lopez, A. (Alexander), Manoochehri, K. (Kia), Marchini, J. (Jonathan), Marcketta, A. (Anthony), Maxwell, E.K. (Evan K.), McCarthy, S. (Shane), Mitnaul, L.J. (Lyndon), O’Dushlaine, C. (Colm), Overton, J.D. (John D.), Padilla, M.S. (Maria Sotiropoulos), Paulding, C. (Charles), Penn, J. (John), Pradhan, M. (Manasi), Reid, J.G. (Jeffrey G.), Schleicher, T.D. (Thomas D.), Schurmann, C. (Claudia), Shuldiner, A. (Alan), Staples, J.C. (Jeffrey C.), Sun, D. (Dylan), Toledo, K. (Karina), Ulloa, R.H. (Ricardo H.), Widom, L. (Louis), Wolf, S.E. (Sarah E.), Yadav, A. (Ashish), Ye, B. (Bin), Rice, K.M. (Kenneth), Ridker, P.M. (Paul M.), Romaine, S.P.R. (Simon P. R.), Rotter, J.I. (Jerome I.), Salo, P. (Perttu), Salomaa, V. (Veikko), Setten, J. (Jessica) van, Shalaby, A.A. (Alaa A.), Smelser, D.T. (Diane T.), Smith, N.L. (Nicholas L.), Stender, S. (Steen), Stott, D.J. (David. J.), Svensson, P. (Per), Tammesoo, M.L., Taylor, K.D. (Kent D.), Teder-Laving, M. (Maris), Teumer, A. (Alexander), Thorgeirsson, G. (Guðmundur), Thorsteinsdottir, U. (Unnur), Torp-Pedersen, C. (Christian Tobias), Trompet, S. (Stella), Tyl, B. (Benoit), Uitterlinden, A.G. (Andre G.), Veluchamy, A. (Abirami), Völker, U. (Uwe), Voors, A.A. (Adriaan A.), Wang, X. (Xiaosong), Wareham, N.J. (Nick), Waterworth, D. (Dawn), Weeke, P.E. (Peter E.), Weiss, R. (Ram), Wiggins, K.L. (Kerri L.), Xing, H. (Heming), Yerges-Armstrong, L.M. (Laura), Yu, B. (Bing), Zannad, F. (Faiez), Zhao, J.H. (Jing Hua), Hemingway, H., Samani, N.J. (Nilesh J.), McMurray, J.J.V. (John J. V.), Yang, J. (Jian), Visscher, P.M. (Peter M.), Newton-Cheh, C. (Christopher), Mälarstig, A. (Anders), Holm, H. (Hilma), Lubitz, S.A. (Steven), Sattar, N. (Naveed), Holmes, M.V. (Michael), Cappola, T.P. (Thomas P.), Asselbergs, F.W. (Folkert), Hingorani, A. (Aroon), Kuchenbaecker, K.B. (Karoline), Ellinor, P.T. (Patrick), Lang, C.C. (Chim C.), Stefansson, K. (Kari), Smith, J.G. (J Gustav), Vasan, R.S. (Ramachandran Srini), Swerdlow, D.I. (Daniel), and Lumbers, R.T. (R. Thomas)
Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
Published: 2020
Full Text: View/download PDF

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

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

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

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

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

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

11. Parental origin of sequence variants associated with complex diseases

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

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

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

13. Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records

Author: Tornio, A., primary, Flynn, R., additional, Morant, S., additional, Velten, E., additional, Palmer, C.N.A., additional, MacDonald, T.M., additional, and Doney, A.S.F., additional
Published: 2017
Full Text: View/download PDF

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

Author: Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), Munroe, P. (Patricia), Berg, M.E. (Marten) van den, Warren, H. (Helen), Cabrera, C.P. (Claudia P.), Verweij, N. (Niek), Mifsud, B. (Borbala), Haessler, J. (Jeff), Bihlmeyer, N.A. (Nathan A.), Fu, Y.-P. (Yi-Ping), Weiss, S. (Stefan), Lin, H.J. (Henry J.), Grarup, N. (Niels), Li-Gao, R. (Ruifang), Pistis, G. (Giorgio), Shah, N. (Nisha), Brody, J.A. (Jennifer A.), Müller-Nurasyid, M. (Martina), Lin, H. (Honghuang), Mei, H. (Hao), Smith, A.V. (Albert V.), Lyytikäinen, L.-P. (Leo-Pekka), Hall, L.M. (Leanne M.), Setten, J. (Jessica) van, Trompet, S. (Stella), Prins, B.P. (Bram P.), Isaacs, A.J. (Aaron), Radmanesh, F. (Farid), Marten, J. (Jonathan), Entwistle, A. (Aiman), Kors, J.A. (Jan), Silva Aldana, C.T. (Claudia), Alonso, A. (Alvaro), Bis, J.C. (Joshua), Boer, R.A. (Rudolf) de, Haan, H.G. (Hugoline) de, Mutsert, R. (Reneé) de, Dedoussis, G.V. (George), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ellinor, P.T. (Patrick), Eppinga, R.N. (Ruben N.), Felix, S.B. (Stephan), Guo, X. (Xiuqing), Hagemeijer, Y. (Yanick), Hansen, T. (T.), Harris, T.B. (Tamara), Heckbert, S.R. (Susan), Huang, P.L. (Paul L.), Hwang, S.-J. (Shih-Jen), Kähönen, M. (Mika), Kanters, J.K., Kolcic, I. (Ivana), Launer, L.J. (Lenore), Li, M. (Man), Yao, J. (Jiefen), Linneberg, A. (Allan), Liu, S. (Simin), MacFarlane, P.W. (Peter), Mangino, M. (Massimo), Morris, A.D. (Andrew D.), Mulas, A. (Antonella), Murray, A.D. (Alison D.), Nelson, C.P. (Christopher P.), Orrù, M. (Marco), Padmanabhan, S. (Sandosh), Peters, A. (Annette), Porteous, D.J. (David J.), Poulter, N.R. (Neil), Psaty, B.M. (Bruce M.), Qi, L. (Lihong), Raitakari, O.T. (Olli T.), Rivadeneira, F. (Fernando), Roselli, C. (Carolina), Rudan, I. (Igor), Sattar, N. (Naveed), Sever, P. (Peter), Sinner, M.F. (Moritz), Soliman, E.Z. (Elsayed), Spector, T.D. (Timothy), Stanton, A. (Alice), Stirrups, K. (Kathy), Taylor, K.D. (Kent), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Vaartjes, I. (Ilonca), Hoes, A.W. (Arno), van der Meer, P. (Peter), Völker, U. (Uwe), Waldenberger, M. (Melanie), Xie, Z. (Zhijun), Zoledziewska, M. (Magdalena), Tinker, A. (Andrew), Polasek, O. (Ozren), Rosand, J. (Jonathan), Jamshidi, Y. (Yalda), Duijn, C.M. (Cornelia) van, Zeggini, E. (Eleftheria), Jukema, J.W. (Jan Wouter), Asselbergs, F.W. (Folkert), Samani, N.J. (Nilesh), Lehtimäki, T. (Terho), Gudnason, V. (Vilmundur), Wilson, J.F. (James), Lubitz, S.A. (Steven A.), Kääb, S. (Stefan), Sotoodehnia, N. (Nona), Caulfield, M. (Mark), Palmer, C.N.A. (Colin), Sanna, S. (Serena), Mook-Kanamori, D.O. (Dennis), Deloukas, P. (Panos), Pedersen, O. (Oluf), Rotter, J.I. (Jerome I.), Dörr, M. (Marcus), O'Donnell, C.J. (Christopher J.), Hayward, C. (Caroline), Arking, D.E. (Dan), Kooperberg, C. (Charles), van der Harst, P. (Pim), Eijgelsheim, M. (Mark), Stricker, B.H.Ch. (Bruno), and Munroe, P. (Patricia)
Abstract: 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
Full Text: View/download PDF

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

Author: Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), Munroe, P. (Patricia), Ehret, G.B. (Georg), Ferreira, T. (Teresa), Chasman, D.I. (Daniel), Jackson, A.U. (Anne), Schmidt, E.M. (Ellen), Johnson, T. (Toby), Thorleifsson, G. (Gudmar), Luan, J. (Jian'An), Donnelly, L.A. (Louise), Kanoni, S. (Stavroula), Petersen, A.K., Pihur, V. (Vasyl), Strawbridge, R.J. (Rona), Shungin, D. (Dmitry), Hughes, M.F. (Maria F.), Meirelles, O., Kaakinen, M. (Marika), Bouatia-Naji, N. (Nabila), Kristiansson, K. (Kati), Shah, S. (Sonia), Kleber, M.E. (Marcus), Guo, X. (Xiuqing), Lyytikäinen, L.-P. (Leo-Pekka), Fava, C. (Cristiano), Eriksson, N. (Niclas), Nolte, I.M. (Ilja), Magnusson, P.K. (Patrik), Salfati, E. (Elias), Rallidis, L.S. (Loukianos), Theusch, E. (Elizabeth), Smith, A.J. (Andrew), Folkersen, L. (Lasse), Witkowska, H.E. (Ewa), Pers, T.H. (Tune), Joehanes, R. (Roby), Kim, S.K. (Stuart K.), Lataniotis, L. (Lazaros), Jansen, R., Johnson, A.D. (Andrew), Warren, H. (Helen), Kim, Y.J., Zhao, W. (Wei), Wu, Y. (Ying), Tayo, B. (Bamidele), Bochud, M. (Murielle), Absher, D. (Devin), Adair, L.S. (Linda), Amin, N. (Najaf), Arking, D.E. (Dan), Axelsson, T. (Tomas), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Bandinelli, S. (Stefania), Barnes, M.J. (Michael), Barroso, I.E. (Inês), Bevan, S. (Stephen), Bis, J.C. (Joshua), Bjornsdottir, G. (Gyda), Boehnke, M. (Michael), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan), Brown, M.J. (Morris), Burnier, M. (Michel), Cabrera, C.P. (Claudia P.), Chambers, J.C. (John), Chang, I.-S. (I-Shou), Cheng, C.-Y. (Ching-Yu), Chines, P.S. (Peter), Chung, R.-H. (Ren-Hua), Collins, F.S. (Francis), Connell, J.M. (John M.), Döring, A. (Angela), Dallongeville, J., Danesh, J. (John), Faire, U. (Ulf) de, Delgado, G., Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Drenos, F. (Fotios), Edkins, T. (Ted), Eicher, J.D. (John D.), Elosua, R. (Roberto), Enroth, S. (Stefan), Erdmann, J. (Jeanette), Eriksson, P. (Per), Esko, T. (Tõnu), Evangelou, E. (Evangelos), Evans, A. (Alun), Fall, M. (Magnus), Farrall, M. (Martin), Felix, J.F. (Janine), Ferrieres, J. (Jean), Ferrucci, L. (Luigi), Fornage, M. (Myriam), Forrester, T. (Terrence), Franceschini, N. (Nora), Franco, O.H. (Oscar), Franco-Cereceda, A. (Anders), Fraser, R.M. (Ross), Ganesh, S.K. (Santhi), Gao, H. (He), Gertow, K. (Karl), Gianfagna, F. (Francesco), Gigante, B. (Bruna), Giulianini, F. (Franco), Goel, A. (Anuj), Goodall, A.H. (Alison), Goodarzi, M. (Mark), Gorski, M. (Mathias), Gräßler, J. (Jürgen), Groves, C.J. (Christopher), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Hallmans, G. (Göran), Hartikainen, A.L., Hassinen, M. (Maija), Havulinna, A.S. (Aki), Hayward, C. (Caroline), Hercberg, S. (Serge), Herzig, K.H., Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hirschhorn, J.N. (Joel), Hofman, A. (Albert), Holmen, J. (Jostein), Holmen, O.L. (Oddgeir), Hottenga, J.J. (Jouke Jan), Howard, P. (Philip), Hsiung, C.A. (Chao A.), Hunt, S.C. (Steven), Ikram, M.K. (Kamran), Illig, T. (Thomas), Iribarren, C. (Carlos), Jensen, R.A. (Richard A.), Kähönen, M. (Mika), Kang, H.M. (Hyun Min), Kathiresan, S. (Sekar), Keating, J. (John), Khaw, K.T., Kim, Y.K. (Yun Kyoung), Kim, E. (Eric), Kivimaki, M. (Mika), Klopp, N. (Norman), Kolovou, G. (Genovefa), Komulainen, P. (Pirjo), Kooner, J.S. (Jaspal S.), Kosova, G. (Gulum), Krauss, R.M. (Ronald), Kuh, D. (Diana), Kutalik, Z. (Zoltán), Kuusisto, J. (Johanna), Kvaløy, K. (Kirsti), Lakka, T.A. (Timo), Lee, N.R. (Nanette), Lee, I.T., Lee, W.-J. (Wen-Jane), Levy, D. (Daniel), Li, X. (Xiaohui), Liang, K.-W. (Kae-Woei), Lin, H. (Honghuang), Lin, L. (Li), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Männistö, S. (Satu), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), MacH, F. (François), Markus, H.S. (Hugh), Marouli, E. (Eirini), McCarthy, M.I. (Mark), McKenzie, C.A. (Colin), Meneton, P. (Pierre), Menni, C. (Cristina), Metspalu, A. (Andres), Mijatovic, V. (Vladan), Moilanen, L. (Leena), Montasser, M.E. (May E.), Morris, A.D. (Andrew), Morrison, A.C. (Alanna), Mulas, A. (Antonella), Nagaraja, R. (Ramaiah), Narisu, N. (Narisu), Nikus, K. (Kjell), O'Donnell, C.J. (Christopher), O'Reilly, P.F. (Paul), Ong, K.K. (Ken), Paccaud, F. (Fred), Palmer, C. (Cameron), Parsa, A. (Afshin), Pedersen, N.L. (Nancy), Penninx, B.W.J.H. (Brenda), Perola, M. (Markus), Peters, A. (Annette), Poulter, N.R. (Neil), Pramstaller, P.P. (Peter Paul), Psaty, B.M. (Bruce), Quertermous, T. (Thomas), Rao, D.C. (Dabeeru C.), Rasheed, A. (Asif), Rayner, N.W. (Nigel William), Renström, F. (Frida), Rettig, R. (Rainer), Rice, K.M. (Kenneth), Roberts, R. (Robert), Rose, L.M. (Lynda), Rossouw, J. (Jacques), Samani, N.J. (Nilesh), Sanna, S. (Serena), Saramies, J. (Jouko), Schunkert, H. (Heribert), Sebert, S. (Sylvain), Sheu, W.H.-H. (Wayne H.-H.), Shin, Y.-A. (Young-Ah), Sim, X. (Xueling), Smith, A.V. (Davey), Smith, A.V. (Albert Vernon), Sosa, M.X. (Maria X.), Spector, T.D. (Timothy), Stancáková, A. (Alena), Stanton, A. (Alice), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swift, A.J. (Amy), Syvänen, A.C., Tai, E.-S. (E-Shyong), Tanaka, T. (Toshiko), Tarasov, K.V. (Kirill), Teumer, A. (Alexander), Thorsteinsdottir, U. (Unnur), Tobin, M.D. (Martin), Tremoli, E. (Elena), Uitterlinden, A.G. (Andre G.), Uusitupa, M. (Matti), Vaez, A. (Ahmad), Vaidya, D. (Dhananjay), Van Duijn, C.M. (Cornelia M.), Iperen, E.P.A. (Erik) van, Vasan, R.S. (Ramachandran S.), Verwoert, G.C. (Germaine), Virtamo, J. (Jarmo), Vitart, V. (Veronique), Voight, B.F. (Benjamin), Vollenweider, P. (Peter), Wagner, A. (Aline), Wain, L.V. (Louise V.), Wareham, N.J. (Nick), Watkins, H. (Hugh), Weder, A.B. (Alan), Westra, H.J. (Harm-Jan), Wilks, R. (Rainford), Wilsgaard, T. (Tom), Wilson, J.F. (James F.), Wong, T.Y. (Tien Y.), Yang, T.-P. (Tsun-Po), Yao, J. (Jiefen), Yengo, L. (Loic), Zhang, W. (Weihua), Zhao, J.H. (Jing Hua), Zhu, X. (Xiaofeng), Bovet, P. (Pascal), Cooper, R.S. (Richard S.), Mohlke, K.L. (Karen), Saleheen, D. (Danish), Lee, J.-Y. (Jong-Young), Elliott, P. (Paul), Gierman, L.M. (Lobke), Willer, C.J. (Cristen), Franke, L. (Lude), Hovingh, G.K. (Kees), Taylor, K.D. (Kent), Dedoussis, G.V. (George), Sever, P. (Peter), Wong, A. (Andrew), Kao, W.H.L. (Wen), Assimes, T.L. (Themistocles), Njølstad, I. (Inger), Schwarz, P.E.H. (Peter), Langenberg, C. (Claudia), Snieder, H. (Harold), Caulfield, M. (Mark), Melander, O. (Olle), Laakso, M. (Markku), Saltevo, J. (Juha), Rauramaa, R. (Rainer), Tuomilehto, J. (Jaakko), Ingelsson, E. (Erik), Lehtimäki, T. (Terho), Hveem, K. (Kristian), Palmas, W. (Walter), März, W. (Winfried), Kumari, M. (Meena), Salomaa, V. (Veikko), Chen, Y.D. (Y.), Rotter, J.I. (Jerome I.), Froguel, P. (Philippe), Jarvelin, M.-R. (Marjo-Riitta), Lakatta, E. (Edward), Kuulasmaa, K. (Kari), Franks, P.W. (Paul), Hamsten, A. (Anders), Wichmann, H.E. (Heinz Erich), Palmer, C.N.A. (Colin), Stefansson, K. (Kari), Ridker, P.M. (Paul), Loos, R.J.F. (Ruth), Chakravarti, A. (Aravinda), Deloukas, P. (Panagiotis), Morris, A.P. (Andrew), Newton-Cheh, C. (C.), and Munroe, P. (Patricia)
Abstract: To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Published: 2016
Full Text: View/download PDF

16. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author: Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), Munroe, P. (Patricia), Surendran, P. (Praveen), Drenos, F. (Fotios), Young, R. (Robin), Warren, H. (Helen), Cook, J.P. (James P.), Manning, A.K. (Alisa), Grarup, N. (Niels), Sim, X. (Xueling), Barnes, D. (Daniel), Witkowska, H.E. (Ewa), Staley, J.R. (James R.), Tragante, V. (Vinicius), Tukiainen, T. (Taru), Yaghootkar, H. (Hanieh), Masca, N. (Nicholas), Freitag, C.M. (Christine), Ferreira, T. (Teresa), Giannakopoulou, O. (Olga), Tinker, A. (Andrew), Harakalova, M. (Magdalena), Mihailov, E. (Evelin), Liu, C. (Chunyu), Kraja, A. (Aldi), Nielsen, S.F. (Sune), Rasheed, A. (Asif), Samuel, M. (Maria), Zhao, W. (Wei), Bonnycastle, L.L. (Lori), Jackson, A.U. (Anne), Narisu, N. (Narisu), Swift, A.J. (Amy), Southam, L. (Lorraine), Marten, J. (Jonathan), Huyghe, J.R. (Jeroen R.), Stancáková, A. (Alena), Fava, C. (Cristiano), Ohlsson, T. (Therese), Matchan, A. (Angela), Stirrups, K. (Kathy), Bork-Jensen, J. (Jette), Gjesing, A.P. (Anette), Kontto, J. (Jukka), Perola, M. (Markus), Shaw-Hawkins, S. (Sue), Havulinna, A.S. (Aki), Zhang, H. (He), Donnelly, L.A. (Louise), Groves, C.J. (Christopher), Rayner, N.W. (Nigel William), Neville, M.J. (Matthew), Robertson, N.R. (Neil), Yiorkas, A.M. (Andrianos M.), Herzig, K.H., Kajantie, E. (Eero), Zhang, W. (Weihua), Willems, S.M. (Sara), Lannfelt, L. (Lars), Malerba, G. (Giovanni), Soranzo, N. (Nicole), Trabetti, E. (Elisabetta), Verweij, N. (Niek), Evangelou, E. (Evangelos), Moayyeri, A. (Alireza), Vergnaud, A.-C. (Anne-Claire), Nelson, C.P. (Christopher P.), Poveda, A. (Alaitz), Varga, T.V. (Tibor V.), Caslake, M. (Muriel), De Craen, A.J.M. (Anton J. M.), Trompet, S. (Stella), Luan, J. (Jian'An), Scott, R.A. (Robert), Harris, S.E. (Sarah), Liewald, D.C.M. (David), Marioni, R.E. (Riccardo), Menni, C. (Cristina), Farmaki, A.-E. (Aliki-Eleni), Hallmans, G. (Göran), Renström, F. (Frida), Huffman, J.E. (Jennifer), Hassinen, M. (Maija), Burgess, S. (Stephen), Vasan, R.S. (Ramachandran S.), Felix, J.F. (Janine), Uria-Nickelsen, M. (Maria), Mälarstig, A. (Anders), Reilly, D.F. (Dermot F.), Hoek, M. (Maarten), Vogt, T.F. (Thomas F.), Lin, H. (Honghuang), Lieb, W. (Wolfgang), Traylor, M. (Matthew), Markus, H.S. (Hugh), Highland, H. (Heather), Justice, A.E. (Anne), Marouli, E. (Eirini), Lindström, J. (Jaana), Uusitupa, M. (Matti), Komulainen, P. (Pirjo), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Polasek, O. (Ozren), Rudan, I. (Igor), Rolandsson, O. (Olov), Franks, P.W. (Paul), Dedoussis, G.V. (George), Spector, T.D. (Timothy), Jousilahti, P. (Pekka), Männistö, S. (Satu), Deary, I.J. (Ian), Starr, J.M. (John), Langenberg, C. (Claudia), Wareham, N.J. (Nick), Brown, M.J. (Morris), Dominiczak, A. (Anna), Connell, J.M. (John M.), Jukema, J.W. (Jan Wouter), Sattar, N. (Naveed), Ford, I. (Ian), Packard, C.J. (Chris J.), Esko, T. (Tõnu), Mägi, R. (Reedik), Metspalu, A. (Andres), Boer, R.A. (Rudolf) de, Van Der Meer, P. (Peter), Harst, P. (Pim) van der, Gambaro, G. (Giovanni), Ingelsson, E. (Erik), Kao, W.H.L. (Wen), Bakker, P.I.W. (Paul) de, Numans, M.E. (Mattijs), Brandslund, I. (Ivan), Christensen, C. (Cramer), Petersen, E.R.B. (Eva R. B.), Korpi-Hyövälti, E. (Eeva), Oksa, H. (Heikki), Chambers, J.C. (John), Kooner, J.S. (Jaspal S.), Blakemore, A.I.F. (Alexandra), Franks, S. (Steve), Jarvelin, M.-R. (Marjo-Riitta), Husemoen, L.L.N. (Lise Lotte), Linneberg, A. (Allan), Skaaby, T. (Tea), Thuesen, B. (Betina), Karpe, F. (Fredrik), Tuomilehto, J. (Jaakko), Doney, A.S.F. (Alex), Morris, A.D. (Andrew), Palmer, C.N.A. (Colin), Holmen, O.L. (Oddgeir), Hveem, K. (Kristian), Willer, C.J. (Cristen), Tuomi, T. (Tiinamaija), Groop, L. (Leif), Käräjämäki, A. (Annemari), Palotie, A. (Aarno), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Alam, D.S. (Dewan S.), Majumder, A.A.S. (Abdulla Al Shafi), Angelantonio, E. (Emanuele) di, Chowdhury, R. (Rajiv), McCarthy, M.I. (Mark), Poulter, N.R. (Neil), Stanton, A. (Alice), Sever, P. (Peter), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Blankenberg, S. (Stefan), Ferrieres, J. (Jean), Kee, F. (Frank), Kuulasmaa, K. (Kari), Müller-Nurasyid, M. (Martina), Veronesi, G. (Giovanni), Virtamo, J. (Jarmo), Deloukas, P. (Panagiotis), Elliott, P. (Paul), Zeggini, E. (Eleftheria), Kathiresan, S. (Sekar), Melander, O. (Olle), Kuusisto, J. (Johanna), Laakso, M. (Markku), Padmanabhan, S. (Sandosh), Porteous, D. (David), Hayward, C. (Caroline), Scotland, G. (Generation), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Hansen, T. (T.), Pedersen, O. (Oluf), Boehnke, M. (Michael), Stringham, H.M. (Heather), Frossard, R., Newton-Cheh, C. (Christopher), Tobin, M.D. (Martin), Nordestgaard, B.G. (Børge), Caulfield, M. (Mark), Mahajan, A. (Anubha), Morris, A.P. (Andrew), Tomaszewski, M. (Maciej), Samani, N.J. (Nilesh), Saleheen, D. (Danish), Asselbergs, F.W. (Folkert), Lindgren, C.M. (Cecilia M.), Danesh, J. (John), Wain, L.V. (Louise V.), Butterworth, A.S. (Adam), Howson, J.M.M. (Joanna M. M.), and Munroe, P. (Patricia)
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
Published: 2016
Full Text: View/download PDF

17. 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, R.J. Dupuis, J. Prokopenko, I. Barker, A. Ahlqvist, E. Rybin, D. Petrie, J.R. Travers, M.E. Bouatia-Naji, N. Dimas, A.S. Nica, A.C. Wheeler, E. Chen, H. Voight, B.F. Taneera, J. Kanoni, S. Peden, J.F. Turrini, F. Gustafsson, S. Zabena, C. Almgren, P. Barker, D.J.P. Barnes, D. Dennison, E.M. Eriksson, J.G. Eriksson, P. Eury, E. Folkersen, L. Fox, C.S. Frayling, T.M. Goel, A. Gu, H.F. Horikoshi, M. Isomaa, B. Jackson, A.U. Jameson, K.A. Kajantie, E. Kerr-Conte, J. Kuulasmaa, T. Kuusisto, J. Loos, R.J.F. Luan, J. Makrilakis, K. Manning, A.K. Martínez-Larrad, M.T. Narisu, N. Mannila, M.N. Öhrvik, J. Osmond, C. Pascoe, L. Payne, F. Sayer, A.A. Sennblad, B. Silveira, A. Stančcáková, A. Stirrups, K. Swift, A.J. Syvänen, A.-C. Tuomi, T. Van't Hooft, F.M. Walker, M. Weedon, M.N. Xie, W. Zethelius, B. Scott, L.J. Steinthorsdottir, V. Morris, A.P. Dina, C. Welch, R.P. Zeggini, E. Huth, C. Aulchenko, Y.S. Thorleifsson, G. Mcculloch, L.J. Ferreira, T. Grallert, H. Amin, N. Wu, G. Willer, C.J. Raychaudhuri, S. McCarroll, S.A. Hofmann, O.M. Qi, L. Segre, A.V. Van Hoek, M. Navarro, P. Ardlie, K. Balkau, B. Benediktsson, R. Bennett, A.J. Blagieva, R. Boerwinkle, E. Bonnycastle, L.L. Bostrom, K.B. Bravenboer, B. Bumpstead, S. Burtt, N.P. Charpentier, G. Chines, P.S. Cornelis, M. Couper, D.J. Crawford, G. Doney, A.S.F. Elliott, K.S. Elliott, A.L. Erdos, M.R. Franklin, C.S. Ganser, M. Gieger, C. Grarup, N. Green, T. Griffin, S. Groves, C.J. Guiducci, C. Hadjadj, S. Hassanali, N. Herder, C. Johnson, P.R.V. Jorgensen, T. Kao, W.H.L. Klopp, N. Kong, A. Kraft, P. Lauritzen, T. Li, M. Lieverse, A. Lindgren, C.M. Lyssenko, V. Marre, M. Meitinger, T. Midthjell, K. Morken, M.A. Nilsson, P. Owen, K.R. Perry, J.R.B. Petersen, A.-K. Platou, C. Proenca, C. Rathmann, W. Rayner, N.W. Robertson, N.R. Rocheleau, G. Roden, M. Sampson, M.J. Saxena, R. Shields, B.M. Shrader, P. Sigurdsson, G. Sparso, T. Strassburger, K. Stringham, H.M. Sun, Q. Thorand, B. Tichet, J. Van Dam, R.M. Van Haeften, T.W. Van Herpt, T. Van Vliet-Ostaptchouk, J.V. Walters, G.B. Wijmenga, C. Witteman, J.C.M. Bergman, R.N. Cauchi, S. Collins, F.S. Gloyn, A.L. Gyllensten, U. Hansen, T. Hide, W.A. Hitman, G.A. Hofman, A. Hunter, D.J. Hveem, K. Laakso, M. Mohlke, K.L. Morris, A.D. Palmer, C.N.A. Pramstaller, P.P. Rudan, I. Sijbrands, E. Stein, L.D. Tuomilehto, J. Uitterlinden, A.G. Wareham, N.J. Watanabe, R.M. Abecasis, G.R. Boehm, B.O. Campbell, H. Daly, M.J. Hattersley, A.T. Hu, F.B. Meigs, J.B. Pankow, J.S. Pedersen, O. Wichmann, H.-E. Barroso, I. Groop, L. Sladek, R. Thorsteinsdottir, U. Wilson, J.F. Illig, T. Froguel, P. Van Duijn, C.M. Stefansson, K. Altshuler, D. Boehnke, M. McCarthy, M.I. Speliotes, E.K. Berndt, S.I. Monda, K.L. Allen, H.L. Magi, R. Randall, J.C. Vedantam, S. Winkler, T.W. Workalemahu, T. Heid, I.M. Wood, A.R. Weyant, R.J. Estrada, K. Liang, L. Nemesh, J. Park, J.-H. Kilpelainen, T.O. Yang, J. Esko, T. Feitosa, M.F. Kutalik, Z. Mangino, M. Scherag, A. Smith, A.V. Zhao, J.H. Aben, K.K. Absher, D.M. Dixon, A.L. Fisher, E. Glazer, N.L. Goddard, M.E. Heard-Costa, N.L. Hoesel, V. Hottenga, J.-J. Johansson, A. Johnson, T. Ketkar, S. Lamina, C. Li, S. Moffatt, M.F. Myers, R.H. Peters, M.J. Preuss, M. Ripatti, S. Rivadeneira, F. Sandholt, C. Timpson, N.J. Tyrer, J.P. Van Wingerden, S. White, C.C. Wiklund, F. Barlassina, C. Chasman, D.I. Cooper, M.N. Jansson, J.-O. Lawrence, R.W. Pellikka, N. Shi, J. Thiering, E. Alavere, H. Alibrandi, M.T.S. Arnold, A.M. Aspelund, T. Atwood, L.D. Balmforth, A.J. Ben-Shlomo, Y. Bergmann, S. Biebermann, H. Blakemore, A.I.F. Boes, T. Bornstein, S.R. Brown, M.J. Buchanan, T.A. Busonero, F. Cappuccio, F.P. Cavalcanti-Proenca, C. Chen, Y.-D.I. Chen, C.-M. Clarke, R. Coin, L. Connell, J. Day, I.N.M. Den Heijer, M. Duan, J. Ebrahim, S. Elliott, P. Elosua, R. Eiriksdottir, G. Facheris, M.F. Felix, S.B. Fischer-Posovszky, P. Folsom, A.R. Friedrich, N. Freimer, N.B. Fu, M. Gaget, S. Gejman, P.V. Geus, E.J.C. Gjesing, A.P. Goyette, P. Grasler, J. Greenawalt, D.M. Gudnason, V. Hartikainen, A.-L. Hall, A.S. Havulinna, A.S. Hayward, C. Heath, A.C. Hengstenberg, C. Hicks, A.A. Hinney, A. Homuth, G. Hui, J. Igl, W. Iribarren, C. Jacobs, K.B. Jarick, I. Jewell, E. John, U. Jousilahti, P. Jula, A. Kaakinen, M. Kaplan, L.M. Kathiresan, S. Kettunen, J. Kinnunen, L. Knowles, J.W. Kolcic, I. König, I.R. Koskinen, S. Kovacs, P. Kvaloy, K. Laitinen, J. Lantieri, O. Lanzani, C. Launer, L.J. Lecoeur, C. Lehtimaki, T. Lettre, G. Liu, J. Lokki, M.-L. Lorentzon, M. Luben, R.N. Ludwig, B. Manunta, P. Marek, D. Martin, N.G. McArdle, W.L. McCarthy, A. McKnight, B. Melander, O. Meyre, D. Montgomery, G.W. Mulic, R. Ngwa, J.S. Nelis, M. Neville, M.J. Nyholt, D.R. O'Donnell, C.J. O'Rahilly, S. Ong, K.K. Oostra, B. Pare, G. Parker, A.N. Perola, M. Pichler, I. Pietilainen, K.H. Platou, C.G.P. Polasek, O. Pouta, A. Rafelt, S. Raitakari, O. Rayner, N.W. Ridderstrale, M. Rief, W. Ruokonen, A. Rzehak, P. Salomaa, V. Sanders, A.R. Sandhu, M.S. Sanna, S. Saramies, J. Savolainen, M.J. Scherag, S. Schipf, S. Schreiber, S. Schunkert, H. Silander, K. Sinisalo, J. Siscovick, D.S. Smit, J.H. Soranzo, N. Sovio, U. Stephens, J. Surakka, I. Tammesoo, M.-L. Tardif, J.-C. Teder-Laving, M. Teslovich, T.M. Thompson, J.R. Thomson, B. Tonjes, A. Van Meurs, J.B.J. Van Ommen, G.-J. Vatin, V. Viikari, J. Visvikis-Siest, S. Vitart, V. Vogel, C.I.G. Waite, L.L. Wallaschofski, H. Widen, E. Wiegand, S. Wild, S.H. Willemsen, G. Witte, D.R. Xu, J. Zhang, Q. Zgaga, L. Ziegler, A. Zitting, P. Beilby, J.P. Farooqi, I.S. Hebebrand, J. Huikuri, H.V. James, A.L. Kahonen, M. Levinson, D.F. Macciardi, F. Nieminen, M.S. Ohlsson, C. Palmer, L.J. Ridker, P.M. Stumvoll, M. Beckmann, J.S. Boeing, H. Boomsma, D.I. Caulfield, M.J. Chanock, S.J. Cupples, L.A. Smith, G.D. Erdmann, J. Gronberg, H. Hall, P. Harris, T.B. Hayes, R.B. Heinrich, J. Jarvelin, M.-R. Kaprio, J. Karpe, F. Khaw, K.-T. Kiemeney, L.A. Krude, H. Lawlor, D.A. Metspalu, A. Munroe, P.B. Ouwehand, W.H. Penninx, B.W. Peters, A. Quertermous, T. Reinehr, T. Rissanen, A. Samani, N.J. Schwarz, P.E.H. Shuldiner, A.R. Spector, T.D. Uda, M. Valle, T.T. Wabitsch, M. Waeber, G. Watkins, H. Wright, A.F. Zillikens, M.C. Chatterjee, N. Purcell, S. Schadt, E.E. Visscher, P.M. Assimes, T.L. Borecki, I.B. Deloukas, P. Haritunians, T. Kaplan, R.C. O'Connell, J.R. Peltonen, L. Schlessinger, D. Strachan, D.P. North, K.E. Hirschhorn, J.N. Ingelsson, E. Parts, L. Glass, D. Nisbet, J. Barrett, A. Sekowska, M. Potter, S. Grundberg, E. Small, K. Hedman, A.K. Bataille, V. Bell, J.T. Surdulescu, G. Ingle, C. Nestle, F.O. Di Meglio, P. Min, J.L. Wilk, A. Hammond, C.J. Yang, T.-P. Montgomery, S.B. Zondervan, K.T. Durbin, R. Ahmadi, K. Dermitzakis, E.T. Reilly, M.P. Holm, H. Stewart, A.F.R. Barbalic, M. Aherrahrou, Z. Allayee, H. Anand, S.S. Andersen, K. Anderson, J.L. Ardissino, D. Ball, S.G. Barnes, T.A. Becker, D.M. Becker, L.C. Berger, K. Bis, J.C. Boekholdt, S.M. Braund, P.S. Burnett, M.S. Buysschaert, I. Carlquist, J.F. Chen, L. Codd, V. Davies, R.W. Cichon, S. Dedoussis, G.V. Demissie, S. Dehghan, A. Devaney, J.M. Diemert, P. Do, R. Doering, A. Eifert, S. El Mokhtari, N.E. Ellis, S.G. Engert, J.C. Epstein, S.E. De Faire, U. Fischer, M. Freyer, J. Gigante, B. Girelli, D. Gretarsdottir, S. Gulcher, J.R. Halperin, E. Hammond, N. Hazen, S.L. Horne, B.D. Jones, G.T. Jukema, J.W. Kaiser, M.A. Kastelein, J.J.P. Kolovou, G. Laaksonen, R. Lambrechts, D. Leander, K. Li, M. Lieb, W. Loley, C. Lotery, A.J. Mannucci, P.M. Maouche, S. Martinelli, N. McKeown, P.P. Meisinger, C. Merlini, P.A. Mooser, V. Morgan, T. Mühleisen, T.W. Muhlestein, J.B. Münzel, T. Musunuru, K. Nahrstaedt, J. Nelson, C.P. Nöthen, M.M. Olivieri, O. Patel, R.S. Patterson, C.C. Peyvandi, F. Qu, L. Quyyumi, A.A. Rader, D.J. Rallidis, L.S. Rice, C. Rosendaal, F.R. Rubin, D. Sampietro, M.L. Sandhu, M.S. Schadt, E. Schäfer, A. Schillert, A. Schrezenmeir, J. Schwartz, S.M. Sivananthan, M. Sivapalaratnam, S. Smith, T.B. Snoep, J.D. Spertus, J.A. Stark, K. Stoll, M. Wilson Tang, W.H. Tennstedt, S. Thorgeirsson, G. Tomaszewski, M. Van Rij, A.M. Wells, G.A. Wild, P.S. Willenborg, C. Wright, B.J. Ye, S. Zeller, T. Cambien, F. Goodall, A.H. Marz, W. Blankenberg, S. Roberts, R. McPherson, R. Hopewell, J.C. Parish, S. Offer, A. Bowman, L. Sleight, P. Armitage, J. Peto, R. Collins, R. Chambers, J.C. Ahmed, N. Donnelly, P. Kooner, A.S. Scott, J. Sehmi, J. Zhang, W. Kooner, J. Sabater-Lleal, M. Mälarstig, A. Hellénius, M.-L. Olsson, G. Rust, S. Assmann, G. Seedorf, U. Barlera, S. Tognoni, G. Franzosi, M.G. Linksted, P. Ongen, H. Kyriakou, T. Green, F. Farrall, M. Saleheen, D. Rasheed, A. Zaidi, M. Shah, N. Samuel, M. Mallick, N. Azhar, M. Zaman, K. Samad, A. Ishaq, M. Gardezi, A. Memon, F.-U.-R. Frossard, P. Danesh, J. Östenson, C.-G. Lind, L. Cooper, C.C. Serrano-Ríos, M. Ferrannini, E. Forsen, T.J. Pattou, F. Langenberg, C. Hamsten, A. Florez, J.C.
Subjects: endocrine system, endocrine system diseases, nutritional and metabolic diseases
Abstract: OBJECTIVE - Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired b-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 3 10-4), improved b-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. © 2011 by the American Diabetes Association.
Published: 2011

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

Author: Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Shungin, D. (Dmitry), Winkler, T.W. (Thomas W.), Croteau-Chonka, D.C. (Damien), Ferreira, T. (Teresa), Locke, A. (Adam), Mägi, R. (Reedik), Strawbridge, R.J. (Rona), Pers, T.H. (Tune), Fischer, K. (Krista), Justice, A.E. (Anne), Workalemahu, T. (Tsegaselassie), Wu, J.M.W. (Joseph M. W.), Buchkovich, M.L. (Martin), Heard-Costa, N.L. (Nancy), Roman, T.S. (Tamara S.), Drong, A. (Alexander), Song, C. (Ci), Gustafsson, S. (Stefan), Day, F.R. (Felix), Esko, T. (Tõnu), Fall, M. (Magnus), Kutalik, Z. (Zolta'n), Luan, J., Randall, J.C. (Joshua), Scherag, A. (Andre), Vedantam, S. (Sailaja), Wood, A.R. (Andrew), Chen, J. (Jin), Fehrmann, R.S.N. (Rudolf), Karjalainen, J. (Juha), Kahali, B. (Bratati), Liu, C.-T. (Ching-Ti), Schmidt, E.M. (Ellen), Absher, D. (Devin), Amin, N. (Najaf), Beekman, M. (Marian), Bragg-Gresham, J.L. (Jennifer L.), Buyske, S. (Steven), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feitosa, M.F. (Mary Furlan), Goel, A. (Anuj), Jackson, A.U. (Anne), Johnson, T. (Toby), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Peters, M.J. (Marjolein), Prokopenko, I. (Inga), Stanca'kova', A. (Alena), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Vliet-Ostaptchouk, J.V. (Jana) van, Yengo, L. (Loic), Zhang, W. (Weihua), Albrecht, E. (Eva), Ärnlöv, J. (Johan), Arscott, G.M. (Gillian M.), Bandinelli, S. (Stefania), Barrett, A. (Angela), Bellis, C. (Claire), Bennett, A.J. (Amanda), Berne, C. (Christian), Blüher, M. (Matthias), Böhringer, S. (Stefan), Bonnet, F. (Fabrice), Böttcher, Y. (Yvonne), Bruinenberg, M. (M.), Carba, D.B. (Delia B.), Caspersen, I.H. (Ida H.), Clarke, R. (Robert), Daw, E.W. (E. Warwick), Deelen, J. (Joris), Deelman, E. (Ewa), Delgado, G., Doney, A.S.F. (Alex), Eklund, N. (Niina), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Eury, E. (Elodie), Friedrich, N. (Nele), Garcia, M. (Melissa), Giedraitis, V. (Vilmantas), Gigante, B. (Bruna), Go, A.T.J.I. (Attie), Golay, A. (Alain), Grallert, H. (Harald), Grammer, T.B. (Tanja), Gräsler, J. (Jürgen), Grewal, J. (Jagvir), Groves, C.J. (Christopher), Haller, T. (Toomas), Hallmans, G. (Göran), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heikkilä, K. (Kauko), Herzig, K.H., Helmer, Q. (Quinta), Hillege, H.L. (Hans), Holmen, O.L. (Oddgeir), Hunt, S.C. (Steven), Isaacs, A. (Aaron), Ittermann, T. (Till), James, A.L. (Alan), Johansson, I. (Inger), Juliusdottir, T. (Thorhildur), Kalafati, I.-P. (Ioanna-Panagiota), Kinnunen, L. (Leena), Koenig, W. (Wolfgang), Kooner, I.K. (Ishminder K.), Kratzer, W. (Wolfgang), Lamina, C. (Claudia), Leander, K. (Karin), Lee, N.R. (Nanette R.), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), MacH, F. (François), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), McArdle, W.L. (Wendy), Menni, C. (Cristina), Merger, S. (Sigrun), Mihailov, E. (Evelin), Milani, L. (Lili), Mills, R. (Rebecca), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Mooijaart, S.P. (Simon), Mühleisen, T.W. (Thomas), Mulas, A. (Antonella), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Nagaraja, R. (Ramaiah), Nalls, M.A. (Michael), Narisu, N. (Narisu), Glorioso, N. (Nicola), Nolte, I.M. (Ilja M.), Olden, M. (Matthias), Rayner, N.W. (Nigel William), Renström, F. (Frida), Ried, J.S. (Janina), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Sennblad, B. (Bengt), Seufferlein, T. (Thomas), Sitlani, C.M. (Colleen), Smith, A.V. (Davey), Stirrups, K. (Kathy), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Swift, A.J. (Amy), Syvanen, A.C., Tayo, B. (Bamidele), Thorand, B. (Barbara), Thorleifsson, G. (Gudmar), Tomaschitz, A. (Andreas), Troffa, C. (Chiara), Oort, F.V.A. (Floor) van, Verweij, N. (Niek), Vonk, J.M. (Judith), Waite, L. (Lindsay), Wennauer, R. (Roman), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Zhang, Q. (Qunyuan), Zhao, J.H. (Jing Hua), Brennan, E.P. (Eoin P.), Choi, M. (Murim), Eriksson, P. (Per), Folkersen, L. (Lasse), Franco-Cereceda, A. (Anders), Gharavi, A.G. (Ali G.), Hedman, A.K. (Asa), Hivert, M.-F. (Marie-France), Huang, J. (Jinyan), Kanoni, S. (Stavroula), Karpe, F. (Fredrik), Keildson, S. (Sarah), Kiryluk, K. (Krzysztof), Liang, L. (Liming), Lifton, R.P. (Richard), Ma, B. (Baoshan), McKnight, A.J. (Amy J.), McPherson, R. (Ruth), Metspalu, A. (Andres), Min, J.L. (Josine L.), Moffatt, M.F. (Miriam), Montgomery, G.W. (Grant), Murabito, J. (Joanne), Nicholson, G. (Ggeorge), Dimas, A.S. (Antigone), Olsson, C. (Christian), Perry, J.R.B. (John), Reinmaa, E. (Eva), Salem, R.M. (Rany), Sandholm, N. (Niina), Schadt, E.E. (Eric), Scott, R.A. (Robert), Stolk, L. (Lisette), Vallejo, E.E. (Edgar E.), Westra, H.J. (Harm-Jan), Zondervan, K.T. (Krina), Amouyel, P. (Philippe), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J.P. (John), Bergman, R.N. (Richard), Blangero, J. (John), Brown, M.J. (Morris), Burnier, M. (Michel), Campbell, H. (Harry), Chakravarti, A. (Aravinda), Chines, P.S. (Peter), Claudi-Boehm, S. (Simone), Collins, F.S. (Francis), Crawford, D.C. (Dana), Danesh, J. (John), Faire, U. (Ulf) de, Geus, E.J.C. (Eco) de, Dörr, M. (Marcus), Erbel, R. (Raimund), Hagen, K. (Knut), Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Forouhi, N.G. (Nita), Forrester, T. (Terrence), Franco, O.H. (Oscar), Gansevoort, R.T. (Ron), Gieger, C. (Christian), Gudnason, V. (Vilmundur), Haiman, C.A. (Christopher), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heliovaara, M. (Markku), Hicks, A.A. (Andrew), Hingorani, A. (Aroon), Hoffmann, W. (Wolfgang), Hofman, A. (Albert), Homuth, G. (Georg), Humphries, S.E. (Steve), Hypponen, E. (Elina), Illig, T. (Thomas), Jarvelin, M.-R. (Marjo-Riitta), Johansen, B. (Berit), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kee, F. (F.), Keinanen-Kiukaanniemi, S. (Sirkka), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuulasmaa, K. (Kari), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lyssenko, V. (Valeriya), Männistö, S. (Satu), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKenzie, C.A. (Colin A.), McKnight, B. (Barbara), Musk, A.W. (Arthur), Möhlenkamp, S. (Stefan), Morris, A.D. (Andrew), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Penninx, B.W.J.H. (Brenda), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), Ridker, P.M. (Paul), Ritchie, M.D. (Marylyn D.), Rudan, I. (Igor), Salomaa, V. (Veikko), Samani, N.J. (Nilesh), Saramies, J. (Jouko), Sarzynski, M.A. (Mark A.), Schwarz, P.E.H. (Peter E. H.), Shuldiner, A.R. (Alan), Staessen, J.A. (Jan), Steinthorsdottir, V. (Valgerdur), Stolk, R.P. (Ronald), Strauch, K. (Konstantin), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Vohl, M.-C. (Marie-Claude), Völker, U. (Uwe), Vollenweider, P. (Peter), Wilson, J.F. (James F), Witteman, J.C.M. (Jacqueline), Adair, L.S. (Linda), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Bornstein, S.R. (Stefan R.), Bouchard, C. (Claude), Cauchi, S. (Ste'phane), Caulfield, M. (Mark), Chambers, J.C. (John C.), Chasman, D.I. (Daniel), Cooper, R.S. (Richard S.), Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Froguel, P. (Philippe), Grabe, H.J. (Hans Jörgen), Hamsten, A. (Anders), Hui, J. (Jennie), Hveem, K. (Kristian), Jöckel, K.-H. (Karl-Heinz), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), März, W. (Winfried), Munroe, P. (Patricia), Njølstad, I. (Inger), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Pedersen, N.L. (Nancy L.), Perola, M. (Markus), Perusse, L. (Louis), Peters, U. (Ulrike), Power, C. (Christopher), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Rivadeneira Ramirez, F. (Fernando), Saaristo, T. (Timo), Saleheen, D., Sinisalo, J. (Juha), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Thorsteinsdottir, U. (Unnur), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Veronesi, G. (Giovanni), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Abecasis, G.R. (Gonçalo), Assimes, T.L. (Themistocles), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), Deloukas, P. (Panagiotis), Franke, L. (Lude), Frayling, T.M. (Timothy), Groop, L. (Leif), Hunter, D. (David), Kaplan, R.C. (Robert), O´Connell, J.R., Qi, L. (Lu), Schlessinger, D. (David), Strachan, D.P. (David), Zwart, J-A. (John-Anker), Duijn, C.M. (Cornelia) van, Willer, C.J. (Cristen), Visscher, P.M. (Peter), Yang, J. (Joanna), Hirschhorn, J.N. (Joel N.), Zillikens, M.C. (Carola), McCarthy, M.I. (Mark), Speliotes, E.K. (Elizabeth), North, K.E. (Kari), Fox, C.S. (Caroline S.), Barroso, I.E. (Inês), Franks, P.W. (Paul), Anderson, D. (Denise), Ingelsson, E. (Erik), Heid, I.M. (Iris), Loos, R.J.F. (Ruth), Cupples, L.A. (Adrienne), Morris, A.P. (Andrew), Lindgren, C.M. (Cecilia), and Mohlke, K.L. (Karen)
Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10-8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015
Full Text: View/download PDF

19. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

Author: Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), Morris, A.P. (Andrew), Gaulton, K. (Kyle), Ferreira, T. (Teresa), Lee, Y. (Yeji), Raimondo, A. (Anne), Mägi, R. (Reedik), Reschen, M.E. (Michael E.), Mahajan, A. (Anubha), Locke, A. (Adam), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Scott, R.A. (Robert), Prokopenko, I. (Inga), Scott, L.J. (Laura), Green, T. (Todd), Sparsø, T. (Thomas), Thuillier, D. (Dorothee), Yengo, L. (Loic), Grallert, H. (Harald), Wahl, S. (Simone), Frånberg, M. (Mattias), Strawbridge, R.J. (Rona), Kestler, H. (Hans), Chheda, H. (Himanshu), Eisele, L. (Lewin), Gustafsson, S. (Stefan), Steinthorsdottir, V. (Valgerdur), Thorleifsson, G. (Gudmar), Qi, L. (Lu), Karssen, L.C. (Lennart), Leeuwen, E.M. (Elisa) van, Willems, S.M. (Sara), Li, M. (Man), Chen, H. (Han), Fuchsberger, C. (Christian), Kwan, P. (Phoenix), Ma, C. (Clement), Linderman, M. (Michael), Lu, Y. (Yingchang), Thomsen, S.K. (Soren K.), Rundle, J.K. (Jana K.), Beer, N.L. (Nicola L.), Bunt, M. (Martijn) van de, Chalisey, A. (Anil), Kang, H.M. (Hyun Min), Voight, B.F. (Benjamin), Abecasis, G.R. (Gonçalo), Almgren, P. (Peter), Baldassarre, D. (Damiano), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Blüher, M. (Matthias), Boeing, H. (Heiner), Bonnycastle, L.L. (Lori), Bottinger, E.P. (Erwin P.), Burtt, N.P. (Noël), Carey, J. (Jason), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David J.), Crenshaw, A. (Andrew), Dam, R.M. (Rob) van, Doney, A.S.F. (Alex), Dorkhan, M. (Mozhgan), Edkins, T. (Ted), Eriksson, J.G. (Johan G.), Esko, T. (Tõnu), Eury, E. (Elodie), Fadista, J. (João), Flannick, J. (Jason), Fontanillas, P. (Pierre), Fox, C.S. (Caroline), Franks, P.W. (Paul W.), Gertow, K. (Karl), Gieger, C. (Christian), Gigante, B. (Bruna), Gottesman, R.F. (Rebecca), Grant, G.B. (George), Grarup, N. (Niels), Groves, C.J. (Christopher J.), Hassinen, M. (Maija), Have, C.T. (Christian T.), Herder, C. (Christian), Holmen, O.L. (Oddgeir), Hreidarsson, A.B. (Astradur), Humphries, S.E. (Steve E.), Hunter, D.J. (David J.), Jackson, A.U. (Anne), Jonsson, A. (Anna), Jørgensen, M.E. (Marit E.), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Kerrison, N.D. (Nicola D.), Kinnunen, L. (Leena), Klopp, N. (Norman), Kong, A. (Augustine), Kovacs, P. (Peter), Kraft, P. (Peter), Kravic, J. (Jasmina), Langford, C. (Cordelia), Leander, K. (Karin), Liang, L. (Liming), Lichtner, P. (Peter), Lindgren, C.M. (Cecilia M.), Lindholm, B. (Bengt), Linneberg, A. (Allan), Liu, C.-T. (Ching-Ti), Lobbens, S. (Stéphane), Luan, J. (Jian'fan), Lyssenko, V. (Valeriya), Männistö, S. (Satu), McLeod, O. (Olga), Meyer, J. (Jobst), Mihailov, E. (Evelin), Mirza, G. (Ghazala), Mühleisen, T.W. (Thomas), Müller-Nurasyid, M. (Martina), Navarro, C. (Carmen), Nöthen, M.M. (Markus), Oskolkov, N.N. (Nikolay N.), Owen, K.R. (Katharine), Palli, D. (Domenico), Pechlivanis, S. (Sonali), Peltonen, L. (Leena Johanna), Perry, J.R.B. (John), Platou, C.P. (Carl), Roden, M. (Michael), Ruderfer, D. (Douglas), Rybin, D. (Denis), Van Der Schouw, Y.T. (Yvonne T.), Sennblad, B. (Bengt), Sigurosson, G. (Gunnar), Stancáková, A. (Alena), Steinbach, D., Storm, P. (Petter), Strauch, K. (Konstantin), Stringham, H.M. (Heather), Sun, Q., Thorand, B. (Barbara), Tikkanen, E. (Emmi), Tönjes, A. (Anke), Trakalo, J. (Joseph), Tremoli, E. (Elena), Tuomi, T. (Tiinamaija), Wennauer, R. (Roman), Wiltshire, S. (Steven), Wood, A.R. (Andrew), Zeggini, E. (Eleftheria), Dunham, I. (Ian), Birney, E. (Ewan), Pasquali, L. (Lorenzo), Ferrer, J. (Jorge), Loos, R.J.F. (Ruth), Dupuis, J. (Josée), Florez, J.C. (Jose), Boerwinkle, E.A. (Eric), Pankow, J.S. (James), Duijn, C.M. (Cornelia) van, Sijbrands, E.J.G. (Eric), Meigs, J.B. (James B.), Hu, F.B. (Frank), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Lakka, T.A. (Timo), Rauramaa, R. (Rainer), Stumvoll, M. (Michael), Pedersen, N.L. (Nancy L.), Lind, L. (Lars), Keinanen-Kiukaanniemi, S. (Sirkka), Korpi-Hyövälti, E. (Eeva), Saaristo, T. (Timo), Saltevo, J. (Juha), Kuusisto, J. (Johanna), Laakso, M. (Markku), Metspalu, A. (Andres), Erbel, R. (Raimund), Jöckel, K.-H. (Karl-Heinz), Moebus, S. (Susanne), Ripatti, S. (Samuli), Salomaa, V. (Veikko), Ingelsson, E. (Erik), Boehm, B.O. (Bernhard), Bergman, R.N. (Richard N.), Collins, F.S. (Francis S.), Mohlke, K.L. (Karen L.), Koistinen, H. (Heikki), Tuomilehto, J. (Jaakko), Hveem, K. (Kristian), Njølstad, I. (Inger), Deloukas, P. (Panagiotis), Donnelly, P.J. (Peter J.), Frayling, T.M. (Timothy), Hattersley, A.T. (Andrew), Faire, U. (Ulf) de, Hamsten, A. (Anders), Illig, T. (Thomas), Peters, A. (Annette), Cauchi, S. (Stephane), Sladek, R. (Rob), Froguel, P. (Philippe), Hansen, T. (Torben), Pedersen, O. (Oluf), Morris, A.D. (Andrew), Palmer, C.N.A. (Collin N. A.), Kathiresan, S. (Sekar), Melander, O. (Olle), Nilsson, P.M. (Peter M.), Groop, L. (Leif), Barroso, I.E. (Inês), Langenberg, C. (Claudia), Wareham, N.J. (Nicholas J.), O'Callaghan, C.A. (Christopher A.), Gloyn, A.L. (Anna), Altshuler, D. (David), Boehnke, M. (Michael), Teslovich, T.M. (Tanya M.), McCarthy, M.I. (Mark), and Morris, A.P. (Andrew)
Abstract: We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
Published: 2015
Full Text: View/download PDF

20. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

Author: Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), Caulfield, M. (Mark), Postmus, D. (Douwe), Trompet, S. (Stella), Deshmukh, H. (Harshal), Barnes, M.J. (Michael), Li, X. (Xiaohui), Warren, H. (Helen), Chasman, D.I. (Daniel), Zhou, K. (Kaixin), Arsenault, B.J. (Benoit J.), Donnelly, L.A. (Louise), Wiggins, K.L. (Kerri), Avery, C.L., Griffin, P. (Paula), Feng, Q. (Qiping), Taylor, K.D. (Kent), Li, G. (Guo), Evans, D.S. (Daniel), Smith, A.V. (Davey), Keyser, C.E. (Catherina Elisabeth) de, Johnson, A.D. (Andrew), Craen, A.J. (Anton) de, Stott, D.J. (David. J.), Buckley, B.M. (Brendan M.), Ford, I., Westendorp, R.G.J. (Rudi), Slagboom, P.E. (Eline), Sattar, N. (Naveed), Munroe, P. (Patricia), Sever, P. (Peter), Poulter, N.R. (Neil), Stanton, A. (Alice), Shields, D.C. (Denis C.), O'Brien, E. (Eoin), Shaw-Hawkins, S. (Sue), Chen, Y.-D.I. (Ida), Nickerson, D.A. (Deborah), Smith, J.D. (Joshua D.), Dubé, G.P. (Gregory), Boekholdt, S.M. (Matthijs), Hovingh, G.K. (Kees), Kastelein, J.J.P. (John), Mckeigue, P.M. (Paul), Betteridge, J. (John), Neil, A. (Andrew), Durrington, P.N. (Paul), Doney, A.S.F. (Alex), Carr, F. (Fiona), Morris, A.D. (Andrew), McCarthy, M.I. (Mark), Groop, L. (Leif), Ahlqvist, E. (Emma), Barroso, I.E. (Inês), Blackwell, K.L. (Kimberly), Bramon, E. (Elvira), Brown, M.A. (Matthew), Casas, J.P. (Juan), Corvin, A. (Aiden), Deloukas, P. (Panagiotis), Duncanson, A. (Audrey), Jankowski, J.A. (Janusz Antoni), Markus, H.S. (Hugh), Mathew, C.G. (Christopher G.), Palmer, C.N.A. (Colin), Plomin, R. (Robert), Rautanen, A. (Anna), Sawcer, S.J. (Stephen), Trembath, R.C. (Richard), Viswanathan, A.C. (Ananth), Wood, N.W. (Nicholas), Spencer, C.C.A. (Chris C.), Band, G. (Gavin), Bellenguez, C. (Céline), Freeman, C. (Colin), Hellenthal, F.A., Giannoulatou, E. (Eleni), Pirinen, M. (Matti), Pearson, R. (Ruth), Strange, A. (Amy), Su, Z. (Zhan), Vukcevic, D. (Damjan), Donnelly, P. (Peter), Langford, C. (Cordelia), Hunt, S.E. (Sarah), Edkins, T. (Ted), Gwilliam, R. (Rhian), Blackburn, H. (Hannah), Bumpstead, S. (Suzannah), Dronov, S. (Serge), Gillman, M. (Matthew), Gray, E. (Emma), Hammond, N. (Naomi), Jayakumar, A. (Alagurevathi), McCann, O.T. (Owen), Liddle, J. (Jennifer), Potter, S.C. (Simon), Ravindrarajah, R. (Radhi), Ricketts, M. (Michelle), Waller, M. (Matthew), Weston, P. (Paul), Widaa, S. (Sara), Whittaker, P. (Pamela), Bis, J.C. (Joshua), Rice, K.M. (Kenneth), Smith, N.L. (Nicholas), Lumley, T. (Thomas), Whitsel, E.A. (Eric), Stürmer, T., Boerwinkle, E.A. (Eric), Ngwa, J.S., O'Donnell, C.J. (Christopher J.), Vasan, R.S. (Ramachandran Srini), Wei, W.-Q. (Wei-Qi), Wilke, R.A. (Russell A.), Liu, C.-T. (Ching-Ti), Sun, F. (Fangui), Guo, X. (Xiuqing), Heckbert, S.R. (Susan), Post, W. (Wendy), Sotoodehnia, N. (Nona), Arnold, A.M. (Alice), Stafford, J.M. (Jeanette M.), Ding, J. (Jingzhong), Herrington, D.M. (David), Kritchevsky, S.B. (Stephen), Eiriksdottir, G. (Gudny), Launer, L.J. (Lenore), Harris, T.B. (Tamara), Chu, A.Y. (Audrey), Giulianini, F. (Franco), MacFadyen, J.G. (Jean G.), Barratt, B.J. (Bryan J.), Nyberg, F. (Fredrik), Stricker, B.H.Ch. (Bruno), Uitterlinden, A.G. (André), Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Emilsson, V. (Valur), Franco, O.H. (Oscar), Ridker, P.M. (Paul), Gudnason, V. (Vilmundur), Liu, Y. (YongMei), Denny, J.C. (Joshua C.), Ballantyne, C. (Christie), Rotter, J.I. (Jerome I.), Cupples, L.A. (Adrienne), Psaty, B.M. (Bruce), Tardif, J.-C. (Jean-Claude), Colhoun, H.M. (H.), Hitman, G.A. (Graham), Krauss, R.M. (Ronald), Jukema, J.W. (Jan Wouter), and Caulfield, M. (Mark)
Published: 2014
Full Text: View/download PDF

21. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

Author: Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), Prokopenko, I. (Inga), Fall, M. (Magnus), Hägg, S. (Sara), Mägi, R. (Reedik), Ploner, A. (Alexander), Fischer, K. (Krista), Horikoshi, M. (Momoko), Sarin, A.-P., Thorleifsson, G. (Gudmar), Ladenvall, C. (Claes), Kals, M. (Mart), Kuningas, M. (Maris), Draisma, G. (Gerrit), Ried, J.S. (Janina), Zuydam, N.R. (Natalie) van, Huikari, V. (Ville), Mangino, M. (Massimo), Sonestedt, E. (Emily), Benyamin, B. (Beben), Nelson, C.P. (Christopher P.), Rivera, N.V. (Natalia), Kristiansson, K. (Kati), Shen, H.-y. (Huei-yi), Havulinna, A.S. (Aki), Dehghan, A. (Abbas), Donnelly, L.A. (Louise), Kaakinen, M. (Marika), Nuotio, M.-L. (Marja-Liisa), Robertson, N. (Neil), Bruijn, R.F.A.G. (Renée) de, Ikram, M.A. (Arfan), Amin, N. (Najaf), Balmforth, A.J. (Anthony), Braund, P.S. (Peter), Doney, A.S.F. (Alex), Döring, A. (Angela), Elliott, P. (Paul), Esko, T. (Tõnu), Franco, O.H. (Oscar), Gretarsdottir, S. (Solveig), Hartikainen, A.L., Heikkilä, K. (Kauko), Herzig, K.H., Holm, H. (Hilma), Hottenga, J.J. (Jouke Jan), Hyppönen, E. (Elina), Illig, T. (Thomas), Isaacs, A.J. (Aaron), Isomaa, B. (Bo), Karssen, L.C. (Lennart), Kettunen, J. (Johannes), Koenig, W. (Wolfgang), Kuulasmaa, K. (Kari), Laatikainen, T. (Tiina), Laitinen, J. (Jaana), Lindgren, C. (Cecilia), Lyssenko, V. (Valeriya), Läärä, E. (Esa), Rayner, N.W. (Nigel William), Männistö, S. (Satu), Pouta, A. (Anneli), Rathmann, W. (Wolfgang), Rivadeneira Ramirez, F. (Fernando), Ruokonen, A. (Aimo), Savolainen, M.J. (Markku), Sijbrands, E.J.G. (Eric), Small, K.S. (Kerrin), Smit, J.H. (Jan), Steinthorsdottir, V. (Valgerdur), Syvanen, A.C., Taanila, A. (Anja), Tobin, M.D. (Martin), Uitterlinden, A.G. (André), Willems, S.M. (Sara), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), Perola, M. (Markus), Evans, A. (Andrew), Ferrières, J. (Jean), Virtamo, J. (Jarmo), Kee, F. (F.), Tregouet, D.-A. (David-Alexandre), Arveiler, D. (Dominique), Amouyel, P. (Philippe), Ferrario, F. (Franco), Brambilla, P. (Paolo), Hall, A. (Anne), Heath, A.C. (Andrew), Madden, P.A.F. (Pamela), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Whitfield, J. (John), Jula, A. (Antti), Knekt, P., Oostra, B.A. (Ben), Duijn, C.M. (Cornelia) van, Penninx, B.W.J.H. (Brenda), Davey-Smith, G. (George), Kaprio, J. (Jaakko), Samani, N.J. (Nilesh), Gieger, C. (Christian), Peters, A. (Annette), Wichmann, H.E. (Heinz Erich), Boomsma, D.I. (Dorret), Geus, E.J.C. (Eco) de, Tuomi, T. (Tiinamaija), Power, C. (Christopher), Hammond, C.J. (Christopher), Spector, T.D. (Timothy), Lind, L. (Lars), Orho-Melander, M. (Marju), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Groop, L. (Leif), Jarvelin, M.-R. (Marjo-Riitta), Salomaa, V. (Veikko), Vartiainen, E. (Erkki), Hofman, A. (Albert), Ripatti, S. (Samuli), Metspalu, A. (Andres), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Pedersen, N.L. (Nancy), McCarthy, M.I. (Mark), Ingelsson, E. (Erik), and Prokopenko, I. (Inga)
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).
Published: 2013
Full Text: View/download PDF

22. Common variants in mendelian kidney disease genes and their association with renal function

Author: Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), Böger, C.A. (Carsten), Parsa, A. (Afshin), Fuchsberger, C. (Christian), Köttgen, A. (Anna), O'Seaghdha, C.M. (Conall), Pattaro, C. (Cristian), Andrade, M. (Mariza) de, Chasman, D.I. (Daniel), Teumer, A. (Alexander), Endlich, K. (Karlhans), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Tin, A. (Adrienne), Kim, Y-J. (Yong-Jin), Taliun, D. (Daniel), Li, M. (Man), Feitosa, M.F. (Mary Furlan), Gorski, M. (Mathias), Yang, Q. (Qiong), Hundertmark, C. (Claudia), Foster, M.C. (Michael), Glazer, N. (Nicole), Isaacs, A.J. (Aaron), Rao, M. (Madhumathi), Smith, A.V. (Davey), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Li, G. (Guo), Hwang, S.J., Atkinson, E.J. (Elizabeth), Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Couraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Deshmukh, H. (Harshal), Ulivi, S. (Shelia), Chu, A.Y. (Audrey), Murgia, D. (Daniela), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, H. (Helena), Hofer, E. (Edith), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Turner, S.T. (Stephen), Ding, J. (Jingzhong), Andrews, J.S. (Jeanette), Freedman, B.I. (Barry), Giulianini, F. (Franco), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Heinz Erich), Zgaga, L. (Lina), Zemunik, T. (Tatijana), Boban, M. (Mladen), Minelli, C. (Cosetta), Wheeler, H.E. (Heather), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Ellinghaus, D. (David), Nöthlings, U. (Ute), Jacobs, G. (Gunnar), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Stracke, S. (Sylvia), Vol̈ker, U. (Uwe), Völzke, H. (Henry), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Helmer, C. (Catherine), Wang, J.J. (Jie Jin), Stengel, B. (Bernd), Ruggiero, D., Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Nikopensius, T. (Tiit), Province, M.A. (Mike), Colhoun, H.M. (H.), Doney, A.S.F. (Alex), Robino, A. (Antonietta), Krämer, B.K. (Bernhard), Portas, L. (Laura), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Adam, M. (Martin), Thun, G.-A. (Gian-Andri), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Mitchell, P. (Paul), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Pirastu, M. (Mario), Jukema, J.W. (Jan Wouter), Probst-Hensch, N.M. (Nicole M.), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Schmidt, R. (Reinhold), Ferrucci, L. (Luigi), Duijn, C.M. (Cornelia) van, Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Liu, Y. (YongMei), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Bochud, M. (Murielle), Heid, I.M. (Iris), Siscovick, D.S. (David), Fox, C.S. (Caroline), Kao, W.H.L. (Wen), and Böger, C.A. (Carsten)
Abstract: Many common genetic variants identified by genome-wide association studies for complex traitsmap to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research. Copyright
Published: 2013
Full Text: View/download PDF

23. Genetic Loci for Retinal Arteriolar Microcirculation

Author: Sim, X. (Xueling), Jensen, R.A. (Richard), Ikram, M.K. (Kamran), Cotch, M.F. (Mary Frances), Li, X. (Xiaohui), MacGregor, S. (Stuart), Xie, J. (Jing), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Mitchell, P. (Paul), Klein, R. (Ronald), Klein, B.E.K. (Barbara), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Launer, L.J. (Lenore), Attia, J. (John), Baird, P.N. (Paul), Harrap, S. (Stephen), Holliday, E.G. (Elizabeth), Inouye, M. (Michael), Rochtchina, E. (Elena), Scott, R.J. (Rodney), Viswanathan, A.C. (Ananth), Li, G. (Guo), Smith, N.L. (Nicholas), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Taylor, K.D. (Kent), Hewit, A.W. (Alex), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Sun, C. (Cong), Young, T.L. (Terri), Mackey, D.A. (David), Zuydam, N.R. (Natalie) van, Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Vingerling, J.R. (Hans), Siscovick, D.S. (David), Wang, J.J. (Jie Jin), Wong, T.Y. (Tien Yin), Sim, X. (Xueling), Jensen, R.A. (Richard), Ikram, M.K. (Kamran), Cotch, M.F. (Mary Frances), Li, X. (Xiaohui), MacGregor, S. (Stuart), Xie, J. (Jing), Smith, A.V. (Albert Vernon), Boerwinkle, E.A. (Eric), Mitchell, P. (Paul), Klein, R. (Ronald), Klein, B.E.K. (Barbara), Glazer, N.L. (Nicole), Lumley, T. (Thomas), McKnight, B. (Barbara), Psaty, B.M. (Bruce), Jong, P.T.V.M. (Paulus) de, Hofman, A. (Albert), Rivadeneira Ramirez, F. (Fernando), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Harris, T.B. (Tamara), Jonasson, F. (Fridbert), Launer, L.J. (Lenore), Attia, J. (John), Baird, P.N. (Paul), Harrap, S. (Stephen), Holliday, E.G. (Elizabeth), Inouye, M. (Michael), Rochtchina, E. (Elena), Scott, R.J. (Rodney), Viswanathan, A.C. (Ananth), Li, G. (Guo), Smith, N.L. (Nicholas), Wiggins, K.L. (Kerri), Kuo, J.Z. (Jane), Taylor, K.D. (Kent), Hewit, A.W. (Alex), Martin, N.G. (Nicholas), Montgomery, G.W. (Grant), Sun, C. (Cong), Young, T.L. (Terri), Mackey, D.A. (David), Zuydam, N.R. (Natalie) van, Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Morris, A.D. (Andrew), Rotter, J.I. (Jerome), Tai, E.S. (Shyong), Gudnason, V. (Vilmundur), Vingerling, J.R. (Hans), Siscovick, D.S. (David), Wang, J.J. (Jie Jin), and Wong, T.Y. (Tien Yin)
Abstract: Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value < 5 x 10(-8) This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value= 2.11 x 10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myoca
Published: 2013
Full Text: View/download PDF

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

Author: Albrechtsen, Anders, Grarup, Niels, Li, Y., Sparsø, Thomas Hempel, Tian, G., Cao, H., Jiang, T., Kim, S.Y., Korneliussen, Thorfinn Sand, Li, Q., Nie, C., Wu, R., Skotte, Line, Morris, A.P., Ladenvall, C., Cauchi, S., Stancáková, A., Andersen, G., Astrup, Arne, Banasik, Karina, Bennett, A.J., Bolund, Lars, Charpentier, G., Chen, Y., Dekker, J.M., Doney, A.S.F., Dorkhan, M., Forsen, T., Frayling, T.M., Groves, C.J., Gui, Y., Hallmans, G., Hattersley, A.T., He, K., Hitman, G.A., Holmkvist, J., Huang, S., Jiang, H., Jin, X., Justesen, Johanne Marie, Kristiansen, Karsten, Kuusisto, J., Lajer, M., Lantieri, O., Li, W., Liang, H., Liao, Q., Liu, X., Ma, T., Ma, X., Manijak, M.P., Marre, M., Mokrosinski, Jacek, Morris, A.D., Mu, B., Nielsen, A.A., Nijpels, G., Nilsson, P., Palmer, C.N.A., Rayner, N.W., Renström, F., Ribel-Madsen, Rasmus, Robertson, N., Rolandsson, O., Rossing, P., Schwartz, Thue W., Slagboom, P.E., Sterner, M., Tang, M., Tarnow, L., Tuomi, T., Van't Riet, E., van Leeuwen, N., Varga, T.V., Vestmar, Marie Aare, Walker, M., Wang, B., Wang, Y., Wu, H., Xi, F., Yengo, L., Yu, C., Zhang, X., Zhang, J., Zhang, Q., Zhang, W., Zheng, H., Zhou, Y., Altshuler, D., 't Hart, L.M., Franks, P.W., Balkau, B., Froguel, P., McCarthy, M.I., Laakso, M., Groop, L., Christensen, C., Brandslund, I., Lauritzen, T., Witte, D.R., Linneberg, A., Jørgensen, Torben, Hansen, Torben, Wang, Jun, Nielsen, Rasmus, Pedersen, Oluf, Albrechtsen, Anders, Grarup, Niels, Li, Y., Sparsø, Thomas Hempel, Tian, G., Cao, H., Jiang, T., Kim, S.Y., Korneliussen, Thorfinn Sand, Li, Q., Nie, C., Wu, R., Skotte, Line, Morris, A.P., Ladenvall, C., Cauchi, S., Stancáková, A., Andersen, G., Astrup, Arne, Banasik, Karina, Bennett, A.J., Bolund, Lars, Charpentier, G., Chen, Y., Dekker, J.M., Doney, A.S.F., Dorkhan, M., Forsen, T., Frayling, T.M., Groves, C.J., Gui, Y., Hallmans, G., Hattersley, A.T., He, K., Hitman, G.A., Holmkvist, J., Huang, S., Jiang, H., Jin, X., Justesen, Johanne Marie, Kristiansen, Karsten, Kuusisto, J., Lajer, M., Lantieri, O., Li, W., Liang, H., Liao, Q., Liu, X., Ma, T., Ma, X., Manijak, M.P., Marre, M., Mokrosinski, Jacek, Morris, A.D., Mu, B., Nielsen, A.A., Nijpels, G., Nilsson, P., Palmer, C.N.A., Rayner, N.W., Renström, F., Ribel-Madsen, Rasmus, Robertson, N., Rolandsson, O., Rossing, P., Schwartz, Thue W., Slagboom, P.E., Sterner, M., Tang, M., Tarnow, L., Tuomi, T., Van't Riet, E., van Leeuwen, N., Varga, T.V., Vestmar, Marie Aare, Walker, M., Wang, B., Wang, Y., Wu, H., Xi, F., Yengo, L., Yu, C., Zhang, X., Zhang, J., Zhang, Q., Zhang, W., Zheng, H., Zhou, Y., Altshuler, D., 't Hart, L.M., Franks, P.W., Balkau, B., Froguel, P., McCarthy, M.I., Laakso, M., Groop, L., Christensen, C., Brandslund, I., Lauritzen, T., Witte, D.R., Linneberg, A., Jørgensen, Torben, Hansen, Torben, Wang, Jun, Nielsen, Rasmus, and Pedersen, Oluf
Abstract: AIMS/HYPOTHESIS: Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes. METHODS: The study comprised three stages. We performed medium-depth (8×) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI >27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p¿1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p¿=¿8.5¿×¿10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p¿=¿1.2¿×¿10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p¿=¿8.2¿×¿10(-10)). CONCLUSIONS/INTERPRETATION: We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
Published: 2013

25. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): A meta-analysis of genome-wide association studies

Author: Traylor, M. (Matthew), Farrall, M. (Martin), Holliday, E.G. (Elizabeth), Sudlow, C. (Cathie), Hopewell, J., Cheng, Y.-C. (Yu-Ching), Fornage, M. (Myriam), Ikram, M.A. (Arfan), Malik, R. (Rainer), Bevan, S. (Steve), Thorsteinsdottir, U. (Unnur), Nalls, M.A. (Michael), Longstreth Jr, W.T., Wiggins, K.L. (Kerri), Yadav, S. (Sunaina), Parati, E.A. (Eugenio), DeStefano, A.L. (Anita), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Khan, M.I. (Muhammad), Reiner, A. (Alexander), Helgadottir, H.T. (Hafdis), Achterberg, S. (Sefanja), Fernandez-Cadenas, I. (Israel), Abboud, S. (Shimon), Schmidt, R. (Reinhold), Walters, M.R. (Matthew), Chen, W-M., Ringelstein, E.B. (E. Bernd), O'Donnell, M. (Martin), Ho, W.K. (Weang Kee), Pera, M.F. (Martin ), Lemmens, R. (Robin), Norrving, B. (Bo), Higgins, P. (Peter), Benn, M. (Marianne), Sale, P. (Patrizio), Kuhlenbäumer, G. (Gregor), Doney, A.S.F. (Alex), Vicente, A.M. (Astrid M), Delavaran, H. (Hossein), Algra, A. (Ale), Davies, G. (Gail), Oliveira, S.A. (Sofia), Palmer, C.N.A. (Colin), Deary, I.J. (Ian), Pandolfo, M. (Massimo), Montaner, J. (Joan), Carty, C. (Cara), Bakker, P.I.W. (Paul) de, Kostulas, K. (Konstantinos), Ferro, M.T. (María), Zuydam, N.R. (Natalie) van, Valdimarsson, E. (Einar), Nordestgaard, B.G. (Børge), Lindgren, A. (Arne), Thijs, V. (Vincent), Slowik, A. (Agnieszka), Saleheen, D., Paré, G. (Guillaume), Berger, K. (Klaus), Thorleifsson, G. (Gudmar), Hofman, A. (Albert), Mosley, T.H. (Thomas), Mitchell, B.D. (Braxton), Furie, K.L. (Karen), Clarke, R. (Robert), Levi, C. (Christopher), Seshadri, S. (Sudha), Gschwendtner, A. (Andreas), Boncoraglio, G. (Giorgio Battista), Sharma, P. (Pankaj), Bis, J.C. (Joshua), Gretarsdottir, S. (Solveig), Psaty, B.M. (Bruce), Rothwell, P.M. (Peter), Rosand, J. (Jonathan), Meschia, J.F. (James F.), Zwart, J-A. (John-Anker), Kubisch, C. (Christian), Markus, H.S. (Hugh), Traylor, M. (Matthew), Farrall, M. (Martin), Holliday, E.G. (Elizabeth), Sudlow, C. (Cathie), Hopewell, J., Cheng, Y.-C. (Yu-Ching), Fornage, M. (Myriam), Ikram, M.A. (Arfan), Malik, R. (Rainer), Bevan, S. (Steve), Thorsteinsdottir, U. (Unnur), Nalls, M.A. (Michael), Longstreth Jr, W.T., Wiggins, K.L. (Kerri), Yadav, S. (Sunaina), Parati, E.A. (Eugenio), DeStefano, A.L. (Anita), Worrall, B.B. (Bradford B.), Kittner, T. (Thomas), Khan, M.I. (Muhammad), Reiner, A. (Alexander), Helgadottir, H.T. (Hafdis), Achterberg, S. (Sefanja), Fernandez-Cadenas, I. (Israel), Abboud, S. (Shimon), Schmidt, R. (Reinhold), Walters, M.R. (Matthew), Chen, W-M., Ringelstein, E.B. (E. Bernd), O'Donnell, M. (Martin), Ho, W.K. (Weang Kee), Pera, M.F. (Martin ), Lemmens, R. (Robin), Norrving, B. (Bo), Higgins, P. (Peter), Benn, M. (Marianne), Sale, P. (Patrizio), Kuhlenbäumer, G. (Gregor), Doney, A.S.F. (Alex), Vicente, A.M. (Astrid M), Delavaran, H. (Hossein), Algra, A. (Ale), Davies, G. (Gail), Oliveira, S.A. (Sofia), Palmer, C.N.A. (Colin), Deary, I.J. (Ian), Pandolfo, M. (Massimo), Montaner, J. (Joan), Carty, C. (Cara), Bakker, P.I.W. (Paul) de, Kostulas, K. (Konstantinos), Ferro, M.T. (María), Zuydam, N.R. (Natalie) van, Valdimarsson, E. (Einar), Nordestgaard, B.G. (Børge), Lindgren, A. (Arne), Thijs, V. (Vincent), Slowik, A. (Agnieszka), Saleheen, D., Paré, G. (Guillaume), Berger, K. (Klaus), Thorleifsson, G. (Gudmar), Hofman, A. (Albert), Mosley, T.H. (Thomas), Mitchell, B.D. (Braxton), Furie, K.L. (Karen), Clarke, R. (Robert), Levi, C. (Christopher), Seshadri, S. (Sudha), Gschwendtner, A. (Andreas), Boncoraglio, G. (Giorgio Battista), Sharma, P. (Pankaj), Bis, J.C. (Joshua), Gretarsdottir, S. (Solveig), Psaty, B.M. (Bruce), Rothwell, P.M. (Peter), Rosand, J. (Jonathan), Meschia, J.F. (James F.), Zwart, J-A. (John-Anker), Kubisch, C. (Christian), and Markus, H.S. (Hugh)
Abstract: Background: Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes. Methods: We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls. Findings: We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10-16) and ZFHX3 (p=2·28×10-8), and for large-vessel stroke at a 9p21 locus (p=3·32×10-5) and HDAC9 (p=2·03×10-12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10-6. However, we were unable to replicate any of these novel associations in the replication cohort. Interpretation: Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes. Funding: Wellcome Trust, UK Medic
Published: 2012
Full Text: View/download PDF

26. Genome-wide association and functional follow-up reveals new loci for kidney function

Author: Pattaro, C. (Cristian), Köttgen, A. (Anna), Teumer, A. (Alexander), Böger, C.A. (Carsten), Fuchsberger, C. (Christian), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Li, M. (Man), Gao, X. (Xiaoyi), Gorski, M. (Mathias), Yang, Q. (Qiong Fang), O'Seaghdha, C.M. (Conall), Glazer, N.L. (Nicole), Isaacs, A.J. (Aaron), Liu, C.-T. (Ching-Ti), Smith, A.V. (Albert Vernon), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Hwang, S.J., Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Chouraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Ulivi, S. (Shelia), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, R. (Reinhold), Cavalieri, M. (Margherita), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Andrade, M. (Mariza) de, Andrews, J.S. (Jeanette), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Erich), Kolcic, I. (Ivana), Zemunik, T. (Tatijana), Boban, M. (Mladen), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Wang, J.J. (Jie Jin), Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Province, M.A. (Mike), Ketkar, S. (Shamika), Doney, A.S.F. (Alex), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Jukema, J.W. (Jan Wouter), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Ferrucci, L. (Luigi), Siscovick, D.S. (David), Tikka-Kleemola, P. (Päivi), Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Parsa, A. (Afshin), Bochud, M. (Murielle), Heid, I.M. (Iris), Goessling, W. (Wolfram), Chasman, D.I. (Daniel), Kao, W.H.L. (Wen), Fox, C.S. (Caroline), Pattaro, C. (Cristian), Köttgen, A. (Anna), Teumer, A. (Alexander), Böger, C.A. (Carsten), Fuchsberger, C. (Christian), Olden, M. (Matthias), Chen, M-H. (Ming-Huei), Li, M. (Man), Gao, X. (Xiaoyi), Gorski, M. (Mathias), Yang, Q. (Qiong Fang), O'Seaghdha, C.M. (Conall), Glazer, N.L. (Nicole), Isaacs, A.J. (Aaron), Liu, C.-T. (Ching-Ti), Smith, A.V. (Albert Vernon), O´Connell, J.R., Struchalin, M.V. (Maksim), Tanaka, T. (Toshiko), Johnson, A.D. (Andrew), Feitosa, M.F. (Mary Furlan), Hwang, S.J., Lohman, K. (Kurt), Cornelis, M. (Marilyn), Johansson, A. (Åsa), Tönjes, A. (Anke), Dehghan, A. (Abbas), Chouraki, V. (Vincent), Holliday, E.G. (Elizabeth), Sorice, R., Kutalik, Z. (Zoltán), Lehtimäki, T. (Terho), Esko, T. (Tõnu), Ulivi, S. (Shelia), Trompet, S. (Stella), Imboden, M. (Medea), Kollerits, B. (Barbara), Pistis, G. (Giorgio), Harris, T.B. (Tamara), Launer, L.J. (Lenore), Aspelund, T. (Thor), Eiriksdottir, G. (Gudny), Mitchell, B.D. (Braxton), Boerwinkle, E.A. (Eric), Schmidt, R. (Reinhold), Cavalieri, M. (Margherita), Hu, F.B. (Frank), Demirkan, A. (Ayşe), Oostra, B.A. (Ben), Andrade, M. (Mariza) de, Andrews, J.S. (Jeanette), Koenig, W. (Wolfgang), Illig, T. (Thomas), Döring, A. (Angela), Wichmann, H.E. (Erich), Kolcic, I. (Ivana), Zemunik, T. (Tatijana), Boban, M. (Mladen), Igl, W. (Wilmar), Zaboli, G. (Ghazal), Wild, S.H. (Sarah), Wright, A.F. (Alan), Campbell, H. (Harry), Biffar, R. (Reiner), Ernst, F.D.J. (Florian), Homuth, G. (Georg), Kroemer, H.K. (Heyo), Nauck, M. (Matthias), Kovacs, P. (Peter), Stumvoll, M. (Michael), Mägi, R. (Reedik), Hofman, A. (Albert), Uitterlinden, A.G. (André), Rivadeneira Ramirez, F. (Fernando), Aulchenko, Y.S. (Yurii), Polasek, O. (Ozren), Hastie, N. (Nick), Vitart, V. (Veronique), Wang, J.J. (Jie Jin), Bergmann, S.M. (Sven), Kähönen, M. (Mika), Viikari, J. (Jorma), Province, M.A. (Mike), Ketkar, S. (Shamika), Doney, A.S.F. (Alex), Ford, I. (Ian), Buckley, B.M. (Brendan M.), Paulweber, B. (Bernhard), Haun, M. (Margot), Sala, C. (Cinzia), Ciullo, M., Vollenweider, P. (Peter), Raitakari, O. (Olli), Metspalu, A. (Andres), Palmer, C.N.A. (Colin), Gasparini, P. (Paolo), Jukema, J.W. (Jan Wouter), Kronenberg, F. (Florian), Toniolo, D. (Daniela), Gudnason, V. (Vilmundur), Shuldiner, A.R. (Alan), Coresh, J. (Josef), Ferrucci, L. (Luigi), Siscovick, D.S. (David), Tikka-Kleemola, P. (Päivi), Borecki, I.B. (Ingrid), Kardia, S.L.R. (Sharon), Curhan, G.C. (Gary), Rudan, I. (Igor), Gyllensten, U. (Ulf), Wilson, J.F. (James), Franke, A. (Andre), Pramstaller, P.P. (Peter Paul), Rettig, R. (Rainer), Prokopenko, I. (Inga), Witteman, J.C.M. (Jacqueline), Hayward, C. (Caroline), Ridker, P.M. (Paul), Parsa, A. (Afshin), Bochud, M. (Murielle), Heid, I.M. (Iris), Goessling, W. (Wolfram), Chasman, D.I. (Daniel), Kao, W.H.L. (Wen), and Fox, C.S. (Caroline)
Abstract: Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.
Published: 2012
Full Text: View/download PDF

27. Genetic association analysis of LARS2 with type 2 diabetes

Author: Reiling, E. (Erwin), Jafar-Mohammadi, B. (Bahram), Riet, E. (Esther) van 't, Weedon, M.N. (Michael), Vliet-Ostaptchouk, J.V. (Jana) van, Hansen, T. (Torben), Saxena, R. (Richa), Haeften, T.W. (Timon) van, Arp, P.P. (Pascal), S. Das, Nijpels, M.G.A.A.M. (Giel), Groenewoud, M.J. (Marlous), Hove, E.C. (Els) van, Uitterlinden, A.G. (André), Smit, J.W.A. (Jan), Morris, A.D. (Andrew), Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Guiducci, C. (Candace), Hattersley, A.T. (Andrew), Frayling, T.M. (Timothy), Pedersen, O. (Oluf), Slagboom, P.E. (Eline), Altshuler, D. (David), Groop, L. (Leif), Romijn, J.A., Maassen, J.A. (Johannes), Hofker, M.A. (Marten), Dekker, J.M. (Jacqueline), McCarthy, M.I. (Mark), Hart, L.M. (Leen) 't, Reiling, E. (Erwin), Jafar-Mohammadi, B. (Bahram), Riet, E. (Esther) van 't, Weedon, M.N. (Michael), Vliet-Ostaptchouk, J.V. (Jana) van, Hansen, T. (Torben), Saxena, R. (Richa), Haeften, T.W. (Timon) van, Arp, P.P. (Pascal), S. Das, Nijpels, M.G.A.A.M. (Giel), Groenewoud, M.J. (Marlous), Hove, E.C. (Els) van, Uitterlinden, A.G. (André), Smit, J.W.A. (Jan), Morris, A.D. (Andrew), Doney, A.S.F. (Alex), Palmer, C.N.A. (Colin), Guiducci, C. (Candace), Hattersley, A.T. (Andrew), Frayling, T.M. (Timothy), Pedersen, O. (Oluf), Slagboom, P.E. (Eline), Altshuler, D. (David), Groop, L. (Leif), Romijn, J.A., Maassen, J.A. (Johannes), Hofker, M.A. (Marten), Dekker, J.M. (Jacqueline), McCarthy, M.I. (Mark), and Hart, L.M. (Leen) 't
Abstract: Aims/hypothesis: LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF>5%) to type 2 diabetes risk. Methods: We combi
Published: 2010
Full Text: View/download PDF

28. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Author: Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), Barroso, I.E. (Inês), Dupuis, J. (Josée), Langenberg, C. (Claudia), Prokopenko, I. (Inga), Saxena, R. (Richa), Soranzo, N. (Nicole), Jackson, A.U. (Anne), Wheeler, E. (Eleanor), Glazer, N.L. (Nicole), Bouatia-Naji, N. (Nabila), Gloyn, A.L. (Anna), Lindgren, C.M. (Cecilia), Mägi, R. (Reedik), Morris, A.P. (Andrew), Randall, J.C. (Joshua), Johnson, T. (Toby), Elliott, P. (Paul), Rybin, D. (Denis), Thorleifsson, G. (Gudmar), Steinthorsdottir, V. (Valgerdur), Henneman, P. (Peter), Grallert, H. (Harald), Dehghan, A. (Abbas), JanHottenga, J. (Jouke), Franklin, C.S. (Christopher), Navarro, P. (Pau), Song, K. (Kijoung), Goel, A. (Anuj), Perry, J.R.B. (John), Egan, J.M. (Josephine), Lajunen, T. (Taina), Grarup, N. (Niels), Sparsø, T. (Thomas), Doney, A.S.F. (Alex), Voight, B.F. (Benjamin), Stringham, H.M. (Heather), Li, M. (Man), Kanoni, S. (Stavroula), Shrader, P. (Peter), Cavalcanti-Proença, C. (Christine), Kumari, M. (Meena), Qi, L. (Lu), Timpson, N.J. (Nicholas), Gieger, C. (Christian), Zabena, C. (Carina), Rocheleau, G. (Ghislain), Ingelsson, E. (Erik), An, P. (Ping), O´Connell, J.R., Luan, J., McCarroll, S.A. (Steven), Payne, F. (Felicity), Roccasecca, R.M., Pattou, F. (François), Sethupathy, P. (Praveen), Ardlie, K.G. (Kristin), Ariyurek, Y. (Yavuz), Balkau, B. (Beverley), Barter, P. (Phil), Beilby, J.P. (John), Ben-Shlomo, Y., Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Bergmann, S.M. (Sven), Bochud, M. (Murielle), Boerwinkle, E.A. (Eric), Bonnefond, A. (Amélie), Bonnycastle, L.L. (Lori), Borch-Johnsen, K., Böttcher, Y. (Yvonne), Brunner, E. (Eric), Bumpstead, S. (Suzannah), Charpentier, G. (Guillaume), IdaChen, Y. (Yii) der, Chines, P.S. (Peter), Clarke, R., McOin, L.J. (Lachlan), Cooper, M.N. (Matthew), Cornelis, M. (Marilyn), Crawford, G. (Gabe), Crisponi, L. (Laura), Day, I.N.M. (Ian), Geus, E.J.C. (Eco) de, Delplanque, J. (Jerome), Dina, C. (Christian), Erdos, M.R. (Michael), Fedson, A.C. (Annette), Fischer-Rosinsky, A. (Antje), Forouhi, N.G. (Nita), Fox, C.S. (Caroline), Frants, R.R. (Rune), GraziaFranzosi, M. (Maria), Galan, P. (Pilar), Goodarzi, M. (Mark), Graessler, J. (Jürgen), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Gwilliam, R. (Rhian), Gyllensten, U. (Ulf), Hadjadj, S. (Samy), Hallmans, G. (Göran), Hammond, N. (Naomi), Han, X. (Xijing), Hartikainen, A.-L. (Anna-Liisa), Hassanali, N. (Neelam), Hayward, C. (Caroline), Heath, S.C. (Simon), Hercberg, S. (Serge), Herder, C. (Christian), Hicks, A.A. (Andrew), Hillman, D.R. (David), Hingorani, A. (Aroon), Hofman, A. (Albert), Hui, J. (Jennie), Hung, J. (Judy), Isomaa, B. (Bo), Jørgensen, T. (Torben), Jula, A. (Antti), Kaakinen, M. (Marika), Kaprio, J. (Jaakko), AnteroKesaniemi, Y., Kivimaki, M. (Mika), Knight, B. (Beatrice), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kyvik, K.O. (Kirsten Ohm), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Bacquer, O.L. (Olivier), Lecoeur, C. (Cécile), Lyssenko, V. (Valeriya), Mahley, R. (Robert), Mangino, M. (Massimo), Manning, A.K. (Alisa), TeresaMartínez-Larrad, M. (María), McAteer, J.B. (Jarred), McCulloch, L.J. (Laura), McPherson, R. (Ruth), Meisinger, C. (Christa), Melzer, D. (David), Meyre, D. (David), Mitchell, B.D. (Braxton), Morken, M.A. (Mario), Mukherjee, S. (Sutapa), Naitza, S. (Silvia), Narisu, N. (Narisu), Neville, M.J. (Matthew), Oostra, B.A. (Ben), Orrù, M. (Marco), Pakyz, R. (Ruth), Palmer, C.N.A. (Colin), Paolisso, G. (Giuseppe), Pattaro, C. (Cristian), Pearson, D. (Daniel), Peden, J. (John), Pedersen, N.L. (Nancy), Perola, M. (Markus), Pfeiffer, A.F.H. (Andreas), Pichler, I. (Irene), Polasek, O. (Ozren), Posthuma, D. (Danielle), Potter, S.C. (Simon), Pouta, A. (Anneli), Province, M.A. (Mike), Psaty, B.M. (Bruce), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Rice, K. (Kenneth), Ripatti, S. (Samuli), Rivadeneira Ramirez, F. (Fernando), Roden, M. (Michael), Rolandsson, O. (Olov), Sandbaek, A. (Annelli), Sandhu, M.S. (Manjinder), Sanna, S. (Serena), Sayer, A.A., Scheet, P. (Paul), Scott, L.J. (Laura), Seedorf, U. (Udo), Sharp, S.J. (Stephen), Shields, B.M. (Beverley), Sigursson, G. (Gunnar), Sijbrands, E.J.G. (Eric), Silveira, A. (Angela), Simpson, L. (Laila), Singleton, A. (Andrew), Smith, N.L. (Nicholas), Sovio, U. (Ulla), Swift, A.J. (Amy), Syddall, H. (Holly), Syvänen, A.-C. (Ann-Christine), Tanaka, T. (Toshiko), Thorand, B. (Barbara), Tichet, J. (Jean), Tönjes, A. (Anke), Tuomi, T. (Tiinamaija), Uitterlinden, A.G. (André), Willems van Dijk, J.A.P. (Ko), Hoek, M. (Mandy) van, Varma, D. (Dhiraj), Visvikis-Siest, S. (Sophie), Vitart, V. (Veronique), Vogelzangs, N. (Nicole), Waeber, G. (Gérard), Wagner, P.J. (Peter), Walley, A. (Andrew), BragiWalters, G., Ward, K.L. (Kim), Watkins, H. (Hugh), Weedon, M.N. (Michael), Wild, S.H. (Sarah), Willemsen, G.A.H.M. (Gonneke), Witteman, J.C.M. (Jacqueline), GYarnell, J.W. (John), Zeggini, E. (Eleftheria), Zelenika, D. (Diana), Zethelius, B. (Björn), Zhai, G. (Guangju), Zhao, J.H. (Jing Hua), Zillikens, M.C. (Carola), Borecki, I.B. (Ingrid), Loos, R.J.F. (Ruth), Meneton, P. (Pierre), Magnusson, P.K. (Patrik), Nathan, D.M. (David), Williams, G.H. (Gordon), Hattersley, A.T. (Andrew), Silander, K. (Kaisa), Salomaa, V. (Veikko), Bornstein, S.R. (Stefan), Schwarz, P. (Peter), Spranger, J. (Jürgen), Karpe, F. (Fredrik), Shuldiner, A.R. (Alan), Dedoussis, G.V. (George), Serrano-Ríos, M. (Manuel), Lind, L. (Lars), Palmer, C. (Cameron), Hu, F.B. (Frank), Franks, P.W. (Paul), Ebrahim, S. (Shanil), Marmot, M. (Michael), Kao, W.-H.L. (Linda), Pankow, J.S. (James), Sampson, M.J. (Michael), Kuusisto, J. (Johanna), Laakso, M. (Markku), Hansen, T. (Torben), Pramstaller, P.P. (Peter Paul), Wichmann, H.E. (Erich), Illig, T. (Thomas), Rudan, I. (Igor), Wright, A.F. (Alan), Stumvoll, M. (Michael), Campbell, H. (Harry), Wilson, J.F. (James), Bergman, R.N. (Richard), Buchanan, T.A. (Thomas), Collins, F.S. (Francis), Mohlke, K.L. (Karen), Tuomilehto, J. (Jaakko), Valle, T.T. (Timo), Altshuler, D. (David), Rotter, J.I. (Jerome), Siscovick, D.S. (David), Penninx, B.W.J.H. (Brenda), Boomsma, D.I. (Dorret), Deloukas, P. (Panagiotis), Spector, T.D. (Timothy), Frayling, T.M. (Timothy), Ferrucci, L. (Luigi), Kong, A. (Augustine), Thorsteinsdottir, U. (Unnur), Zwart, J-A. (John-Anker), Tikka-Kleemola, P. (Päivi), Aulchenko, Y.S. (Yurii), Cao, A. (Antonio), Scuteri, A. (Angelo), Schlessinger, D. (David), Uda, M. (Manuela), Ruokonen, A. (Aimo), Jarvelin, M.-R. (Marjo-Riitta), Waterworth, D. (Dawn), Vollenweider, P. (Peter), Peltonen, L. (Leena Johanna), Mooser, V. (Vincent), Abecasis, G.R. (Gonçalo), Wareham, N.J. (Nick), Sladek, R. (Rob), Froguel, P. (Philippe), Meigs, J.B. (James), Groop, L. (Leif), Watanabe, R.M. (Richard), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Florez, J.C. (Jose), and Barroso, I.E. (Inês)
Abstract: Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
Published: 2010
Full Text: View/download PDF

29. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

Author: Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), Watanabe, R.M. (Richard), Voight, B.F. (Benjamin), Scott, L.J. (Laura), Steinthorsdottir, V. (Valgerdur), Morris, A.D. (Andrew), Dina, C. (Christian), Welch, R.P. (Ryan), Zeggini, E. (Eleftheria), Huth, C. (Cornelia), Aulchenko, Y.S. (Yurii), Thorleifsson, G. (Gudmar), McCulloch, L.J. (Laura), Ferreira, T. (Teresa), Grallert, H. (Harald), Amin, N. (Najaf), Wu, G. (Guanming), Willer, C.J. (Cristen), Raychaudhuri, S. (Soumya), McCarroll, S.A. (Steven), Langenberg, C. (Claudia), Hofmann, O.M. (Oliver), Dupuis, J. (Josée), Qi, L. (Lu), Segrè, A.V. (Ayellet), Hoek, M. (Mandy) van, Navarro, P. (Pau), Ardlie, K.G. (Kristin), Balkau, B. (Beverley), Benediktsson, R. (Rafn), Bennett, A.J. (Amanda), Blagieva, R. (Roza), Boerwinkle, E.A. (Eric), Bonnycastle, L.L. (Lori), Boström, K.B. (Kristina Bengtsson), Bravenboer, B. (Bert), Bumpstead, S. (Suzannah), Burtt, N.P. (Noël), Charpentier, G. (Guillaume), Chines, P.S. (Peter), Cornelis, M. (Marilyn), Couper, D.J. (David), Crawford, G. (Gabe), Doney, A.S.F. (Alex), Elliott, K.S. (Katherine), Erdos, M.R. (Michael), Fox, C.S. (Caroline), Franklin, C.S. (Christopher), Ganser, M. (Martha), Gieger, C. (Christian), Grarup, N. (Niels), Green, T. (Todd), Griffin, S. (Simon), Groves, C.J. (Christopher), Guiducci, C. (Candace), Hadjadj, S. (Samy), Hassanali, N. (Neelam), Herder, C. (Christian), Isomaa, B. (Bo), Jackson, A.U. (Anne), Johnson, P.R.V. (Paul), Jørgensen, T. (Torben), Kao, W.H.L. (Wen), Klopp, N. (Norman), Kong, A. (Augustine), Kraft, P. (Peter), Kuusisto, J. (Johanna), Lauritzen, T. (Torsten), Li, M. (Man), Lieverse, A.G. (Aloysius), Lindgren, C.M. (Cecilia), Lyssenko, V. (Valeriya), Marre, M. (Michel), Meitinger, T. (Thomas), Midthjell, K. (Kristian), Morken, M.A. (Mario), Narisu, N. (Narisu), Nilsson, P. (Peter), Owen, K.R. (Katharine), Payne, F. (Felicity), Perry, J.R.B. (John), Petersen, A.K., Platou, C. (Carl), Proença, C. (Christine), Prokopenko, I. (Inga), Rathmann, W. (Wolfgang), Rayner, N.W. (Nigel William), Robertson, N.R. (Neil), Rocheleau, G. (Ghislain), Roden, M. (Michael), Sampson, M.J. (Michael), Saxena, R. (Richa), Shields, B.M. (Beverley), Shrader, P. (Peter), Sigurdsson, G. (Gunnar), Sparsø, T. (Thomas), Strassburger, K. (Klaus), Stringham, H.M. (Heather), Sun, Q. (Qi), Swift, A.J. (Amy), Thorand, B. (Barbara), Tichet, J. (Jean), Tuomi, T. (Tiinamaija), Dam, R.M. (Rob) van, Haeften, T.W. (Timon) van, Herpt, T.W. (Thijs) van, Vliet-Ostaptchouk, J.V. (Jana) van, Walters, G.B. (Bragi), Weedon, M.N. (Michael), Wijmenga, C. (Cisca), Witteman, J.C.M. (Jacqueline), Bergman, R.N. (Richard), Cauchi, S. (Stephane), Collins, F.S. (Francis), Gloyn, A.L. (Anna), Gyllensten, U. (Ulf), Hansen, T. (Torben), Hide, W.A. (Winston), Hitman, G.A. (Graham), Hofman, A. (Albert), Hunter, D. (David), Hveem, K. (Kristian), Laakso, M. (Markku), Mohlke, K.L. (Karen), Palmer, C.N.A. (Colin), Pramstaller, P.P. (Peter Paul), Rudan, I. (Igor), Sijbrands, E.J.G. (Eric), Stein, L.D. (Lincoln), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Walker, M. (Mark), Wareham, N.J. (Nick), Abecasis, G.R. (Gonçalo), Boehm, B.O. (Bernhard), Campbell, H. (Harry), Daly, M.J. (Mark), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Meigs, J.B. (James), Pankow, J.S. (James), Pedersen, O. (Oluf), Wichmann, H.E. (Erich), Barroso, I.E. (Inês), Florez, J.C. (Jose), Frayling, T.M. (Timothy), Groop, L. (Leif), Sladek, R. (Rob), Thorsteinsdottir, U. (Unnur), Wilson, J.F. (James), Illig, T. (Thomas), Froguel, P. (Philippe), Tikka-Kleemola, P. (Päivi), Zwart, J-A. (John-Anker), Altshuler, D. (David), Boehnke, M. (Michael), McCarthy, M.I. (Mark), and Watanabe, R.M. (Richard)
Abstract: By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P 5 × 10 8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap
Published: 2010
Full Text: View/download PDF

30. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

Author: Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), McCarthy, M.I. (Mark), Lindgren, C.M. (Cecilia), Heid, I.M. (Iris), Randall, J.C. (Joshua), Lamina, C. (Claudia), Steinthorsdottir, V. (Valgerdur), Qi, L. (Lu), Speliotes, E.K. (Elizabeth), Thorleifsson, G. (Gudmar), Willer, C.J. (Cristen), Herrera, B.M. (Blanca), Jackson, A.U. (Anne), Lim, N. (Noha), Scheet, P. (Paul), Soranzo, N. (Nicole), Amin, N. (Najaf), Aulchenko, Y.S. (Yurii), Chambers, J.C. (John), Drong, A. (Alexander), Luan, J., Lyon, H.N. (Helen), Rivadeneira Ramirez, F. (Fernando), Sanna, S. (Serena), Timpson, N.J. (Nicholas), Zillikens, M.C. (Carola), Jing, H.Z., Almgren, P. (Peter), Bandinelli, S. (Stefania), Bennett, A.J. (Amanda), Bergman, R.N. (Richard), Bonnycastle, L.L. (Lori), Bumpstead, S. (Suzannah), Chanock, S.J. (Stephen), Cherkas, L. (Lynn), Chines, P.S. (Peter), Coin, L. (Lachlan), Cooper, C. (Charles), Crawford, G. (Gabe), Doering, A. (Angela), Dominiczak, A. (Anna), Doney, A.S.F. (Alex), Ebrahim, S. (Shanil), Elliott, P. (Paul), Erdos, M.R. (Michael), Estrada Gil, K. (Karol), Ferrucci, L. (Luigi), Fischer, G. (Guido), Forouhi, N.G. (Nita), Gieger, C. (Christian), Grallert, H. (Harald), Groves, C.J. (Christopher), Grundy, S.M. (Scott), Guiducci, C. (Candace), Hadley, D. (David), Hamsten, A. (Anders), Havulinna, A.S. (Aki), Hofman, A. (Albert), Holle, R. (Rolf), Holloway, J.W. (John), Illig, T. (Thomas), Isomaa, B. (Bo), Jacobs, L.C. (Leonie), Jameson, K. (Karen), Jousilahti, P. (Pekka), Karpe, F. (Fredrik), Kuusisto, J. (Johanna), Laitinen, J. (Jaana), Lathrop, G.M. (Mark), Lawlor, D.A. (Debbie), Mangino, M. (Massimo), McArdle, W.L. (Wendy), Meitinger, T. (Thomas), Morken, M.A. (Mario), Morris, A.P. (Andrew), Munroe, P. (Patricia), Narisu, N. (Narisu), Nordström, A. (Anna), Oostra, B.A. (Ben), Palmer, C.N.A. (Colin), Payne, F. (Felicity), Peden, J. (John), Prokopenko, I. (Inga), Renström, F. (Frida), Ruokonen, A. (Aimo), Salomaa, V. (Veikko), Sandhu, M.S. (Manjinder), Scott, L.J. (Laura), Scuteri, A. (Angelo), Silander, K. (Kaisa), Song, K. (Kijoung), Yuan, X. (Xin), Stringham, H.M. (Heather), Swift, A.J. (Amy), Tuomi, T. (Tiinamaija), Uda, M. (Manuela), Vollenweider, P. (Peter), Waeber, G. (Gérard), Wallace, C. (Chris), Walters, G.B. (Bragi), Weedon, M.N. (Michael), Witteman, J.C.M. (Jacqueline), Zhang, C. (Cuilin), Caulfield, M. (Mark), Collins, F.S. (Francis), Smith, A.V. (Davey), Day, I.N.M. (Ian), Franks, P.W. (Paul), Hattersley, A.T. (Andrew), Hu, F.B. (Frank), Jarvelin, M.-R. (Marjo-Riitta), Kong, A. (Augustine), Kooner, J.S. (Jaspal), Laakso, M. (Markku), Lakatta, E. (Edward), Mooser, V. (Vincent), Peltonen, L. (Leena Johanna), Samani, N.J. (Nilesh), Spector, T.D. (Timothy), Strachan, D.P. (David), Tanaka, T. (Toshiko), Tuomilehto, J. (Jaakko), Uitterlinden, A.G. (André), Tikka-Kleemola, P. (Päivi), Wareham, N.J. (Nick), Watkins, H. (Hugh), Waterworth, D. (Dawn), Boehnke, M. (Michael), Deloukas, P. (Panagiotis), Groop, L. (Leif), Hunter, D.J. (David), Thorsteinsdottir, U. (Unnur), Schlessinger, D. (David), Wichmann, H.E. (Erich), Frayling, T.M. (Timothy), Abecasis, G.R. (Gonçalo), Hirschhorn, J.N. (Joel), Loos, R.J.F. (Ruth), Zwart, J-A. (John-Anker), Mohlke, K.L. (Karen), Barroso, I.E. (Inês), and McCarthy, M.I. (Mark)
Abstract: To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×102-11) and MSRA (WC, P = 8.9×10-9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10-8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human
Published: 2009
Full Text: View/download PDF

31. Variants in MTNR1B influence fasting glucose levels

Author: Prokopenko, I., Langenberg, C., Florez, J.C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R.J.F., Manning, A.K., Jackson, A.U., Aulchenko, Y.S., Potter, S.C., Erdos, M.R., Sanna, S., Hottenga, J.J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., Beckmann, J.S., Bergman, R.N., Bochud, M., Bonnycastle, L.L., Buchanan, T.A., Cao, A., Cervin, A., Coin, L., Collins, F.S., Crisponi, L., de Geus, E.J.C., Dehghan, A., Deloukas, P., Doney, A.S.F., Elliott, P., Freimer, N.B., Gateva, V., Herder, C., Hofman, A., Hughes, T.E., Hunt, S., Illig, T., Inouye, M., Isomaa, B., Johnson, T., Kong, A., Krestyaninova, M., Kuusisto, J., Laaks, M., Lim, N., Lindblad, U., Lindgren, C.M., McCann, O.T., Mohlke, K.L., Morris, A.D., Naitza, S., Orrù, M., Palmer, C.N.A., Pouta, A., Randall, J., Rathmann, W., Saramies, J., Scheet, P., Scott, L.J., Scuteri, A., Sharp, S., Sijbrands, E.J.G., Smit, J.H., Song, K., Steinthorsdottir, V., Stringham, H.M., Tuomi, T., Tuomilehto, J., Uitterlinden, A.G., Voight, B.F., Waterworth, D., Wichmann, H.-E., Willemsen, G., Witteman, J.C.M., Yuan, X., Zha, J.H., Zeggini, E., Schlessinger, D., Sandhu, M., Boomsma, D.I., Uda, M., Spector, T.D., Penninx, B.W.J.H., Altshuler, D., Vollenweider, P., Jarvelin, M.-R., Lakatta, E., Waeber, G., Fox, C.S., Peltonen, L., Groop, L.C., Mooser, V., Cupples, L.A., Thorsteinsdottir, U., Abecasis, G.R., Prokopenko, I., Langenberg, C., Florez, J.C., Saxena, R., Soranzo, N., Thorleifsson, G., Loos, R.J.F., Manning, A.K., Jackson, A.U., Aulchenko, Y.S., Potter, S.C., Erdos, M.R., Sanna, S., Hottenga, J.J., Wheeler, E., Kaakinen, M., Lyssenko, V., Chen, W.-M., Ahmadi, K., Beckmann, J.S., Bergman, R.N., Bochud, M., Bonnycastle, L.L., Buchanan, T.A., Cao, A., Cervin, A., Coin, L., Collins, F.S., Crisponi, L., de Geus, E.J.C., Dehghan, A., Deloukas, P., Doney, A.S.F., Elliott, P., Freimer, N.B., Gateva, V., Herder, C., Hofman, A., Hughes, T.E., Hunt, S., Illig, T., Inouye, M., Isomaa, B., Johnson, T., Kong, A., Krestyaninova, M., Kuusisto, J., Laaks, M., Lim, N., Lindblad, U., Lindgren, C.M., McCann, O.T., Mohlke, K.L., Morris, A.D., Naitza, S., Orrù, M., Palmer, C.N.A., Pouta, A., Randall, J., Rathmann, W., Saramies, J., Scheet, P., Scott, L.J., Scuteri, A., Sharp, S., Sijbrands, E.J.G., Smit, J.H., Song, K., Steinthorsdottir, V., Stringham, H.M., Tuomi, T., Tuomilehto, J., Uitterlinden, A.G., Voight, B.F., Waterworth, D., Wichmann, H.-E., Willemsen, G., Witteman, J.C.M., Yuan, X., Zha, J.H., Zeggini, E., Schlessinger, D., Sandhu, M., Boomsma, D.I., Uda, M., Spector, T.D., Penninx, B.W.J.H., Altshuler, D., Vollenweider, P., Jarvelin, M.-R., Lakatta, E., Waeber, G., Fox, C.S., Peltonen, L., Groop, L.C., Mooser, V., Cupples, L.A., Thorsteinsdottir, U., and Abecasis, G.R.
Abstract: To identify previously unknown genetic loci associated with fasting glucose concentrations, we examined the leading association signals in ten genome-wide association scans involving a total of 36,610 individuals of European descent. Variants in the gene encoding melatonin receptor 1B (MTNR1B) were consistently associated with fasting glucose across all ten studies. The strongest signal was observed at rs10830963, where each G allele (frequency 0.30 in HapMap CEU) was associated with an increase of 0.07 (95% CI = 0.06-0.08) mmol/l in fasting glucose levels (P = 3.2 × 10
Published: 2009
Full Text: View/download PDF

32. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

Author: Surendran, P., Drenos, F., Young, R., Warren, H., Cook, J.P., Manning, A.K., Grarup, N., Sim, X., Barnes, D.R., Witkowska, K., Staley, J.R., Tragante, V., Tukiainen, T., Yaghootkar, H., Masca, N., Freitag, D.F., Ferreira, T., Giannakopoulou, O., Tinker, A., Harakalova, M., Mihailov, E., Liu, C., Kraja, A.T., Nielsen, S.F., Rasheed, A., Samue, M., Zhao, W., Bonnycastle, L.L., Jackson, A.U., Narisu, N., Swift, A.J., Southam, L., Marten, J., Huyghe, J.R., Stancakova, A., Fava, C., Ohlsson, T., Matchan, A., Stirrups, K.E., Bork-Jensen, J., Gjesing, A.P., Kontto, J., Perola, M., Shaw-Hawkins, S., Havulinna, A.S., Zhang, H., Donnelly, L.A., Groves, C.J., Rayner, N.W., Neville, M.J., Robertson, N.R., Yiorkas, A.M., Herzig, K.H., Kajantie, E., Zhang, W., Willems, S.M., Lannfelt, L., Malerba, G., Soranzo, N., Trabetti, E., Verweij, N., Evangelou, E., Moayyeri, A., Vergnaud, A.C., Nelson, C.P., Poveda, A., Varga, T.V., Caslake, M., Craen, A.J.M. de, Trompet, S., Luan, J., Scott, R.A., Harris, S.E., Liewald, D.C.M., Marioni, R., Menni, C., Farmaki, A.E., Hallmans, G., Renstrom, F., Huffman, J.E., Hassinen, M., Burgess, S., Vasan, R.S., Felix, J.F., Uria-Nickelsen, M., Malarstign, A., Reilly, D.F., Hoek, M., Vogt, T.F., Lin, H.H., Lieb, W., Traylor, M., Markus, H.S., Highland, H.M., Justice, A.E., Marouli, E., Lindstrom, J., Uusitupa, M., Komulainen, P., Lakka, T.A., Rauramaa, R., Polasek, O., Rudan, I., Rolandsson, O., Franks, P.W., Dedoussis, G., Spector, T.D., Jousilahti, P., Mannisto, S., Deary, I.J., Starr, J.M., Langenberg, C., Wareham, N.J., Brown, M.J., Dominiczak, A.F., Connell, J.M., Jukema, J.W., Sattar, N., Ford, I., Packard, C.J., Esko, T., Magi, R., Metspalu, A., Boer, R.A. de, Meer, P. van der, Harst, P. van der, Gambaro, G., Ingelsson, E., Lind, L., Bakker, P.I.W. de, Numans, M.E., Brandslund, I., Christensen, C., Petersen, E.R.B., Korpi-Hyovalti, E., Oksa, H., Chambers, J.C., Kooner, J.S., Blakemore, A.I.F., Franks, S., Jarvelin, M.R., Husemoen, L.L., Linneberg, A., Skaaby, T., Thuesen, B., Karpe, F., Tuomilehto, J., Doney, A.S.F., Morris, A.D., Palmer, C.N.A., Holmen, O.L., Hveem, K., Willer, C.J., Tuomi, T., Groop, L., Karajamaki, A., Palotie, A., Ripatti, S., Salomaa, V., Alam, D.S., Majmnder, A.A.S., Angelantonio, E. di, Chowdhury, R., McCarthy, M.I., Poulter, N., Stanton, A.V., Sever, P., Amouyel, P., Arveiler, D., Blankenberg, S., Ferrieres, J., Kee, F., Kuulasmaa, K., Muller-Nurasyid, M., Veronesi, G., Virtamo, J., Deloukas, P., Elliott, P., Zeggini, E., Kathiresan, S., Melander, O., Kuusisto, J., Laakso, M., Padmanabhan, S., Porteous, D.J., Hayward, C., Scotland, G., Collins, F.S., Mohlke, K.L., Hansen, T., Pedersen, O., Boehnke, M., Stringham, H.M., Frossard, P., Newton-Cheh, C., Tobin, M.D., Nordestgaard, B.G., Caulfield, M.J., Mahajan, A., Morris, A.P., Tomaszewski, M., Samani, N.J., Saleheen, D., Asselbergs, F.W., Lindgren, C.M., Danesh, J., Wain, L.V., Butterworth, A.S., Howson, J.M.M., Munroe, P.B., CHARGE Heart Failure Consortiumm, EchoGen Consortiumm, Metastroke Consortiumm, Giant Consortiumm, EPIC-InterAct Consortium, Lifelines Cohort Study, Wellcome Trust Case Control Consor, Understanding Soc Sci Grp, EPIC-CVD Consortium, CHARGE Exome Chip Blood Pressure C, T2D-GENES Consortium, GoT2DGenes Consortium, ExomeBP Consortium, CHD Exome Consortium, Erasmus MC other, Epidemiology, Internal Medicine, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Surendran, Praveen [0000-0002-4911-6077], Barnes, Daniel [0000-0002-3781-7570], Marten, Jonathan [0000-0001-6916-2014], Johnson, Kathleen [0000-0002-6823-3252], Soranzo, Nicole [0000-0003-1095-3852], Luan, Jian'an [0000-0003-3137-6337], Burgess, Stephen [0000-0001-5365-8760], Traylor, Matthew [0000-0001-6624-8621], Markus, Hugh [0000-0002-9794-5996], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Di Angelantonio, Emanuele [0000-0001-8776-6719], Chowdhury, Rajiv [0000-0003-4881-5690], Danesh, John [0000-0003-1158-6791], Butterworth, Adam [0000-0002-6915-9015], Howson, Joanna [0000-0001-7618-0050], Apollo - University of Cambridge Repository, British Heart Foundation, Home Office, Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, and Action on Hearing Loss
Subjects: 0301 basic medicine, EchoGen Consortium, Population genetics, LOCI, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Bioinformatics, Genome-wide association studies, 0302 clinical medicine, Settore MED/14 - NEFROLOGIA, Missense mutation, GENE-CENTRIC ARRAY, GoT2DGenes Consortium, AGING RESEARCH, Genetics, education.field_of_study, CHD Exome+ Consortium, CHARGE-Heart Failure Consortium, 11 Medical And Health Sciences, 3. Good health, CARDIOVASCULAR-DISEASE, Hypertension, Medical genetics, HEART, Wellcome Trust Case Control Consortium, EPIC-InterAct Consortium, ExomeBP Consortium, CHARGE, Understanding Society Scientific Group, medicine.medical_specialty, Genotype, Population, Biology, CHARGE+ Exome Chip Blood Pressure Consortium, EPIC-CVD Consortium, Article, 03 medical and health sciences, Lifelines Cohort Study, genome-wide association studies, hypertension, population genetics, Genetic variation, GIANT Consortium, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Allele, GENOME-WIDE ASSOCIATION, education, PLASMA-LEVELS, IDENTIFICATION, Genetic Variation, 06 Biological Sciences, medicine.disease, METASTROKE Consortium, T2D-GENES Consortium, 030104 developmental biology, Blood pressure, Pathophysiology of hypertension, RISK-FACTORS, Developmental Biology, Genome-Wide Association Study, blood pressure, gene
Abstract: High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ~155,063 samples for independent replication. We identified 30 new blood pressure– or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention. N.P. has received financial support from several pharmaceutical companies that manufacture either blood pressure -lowering or lipid-lowering agents, or both, and consultancy fees. S.K. has received research grants from Merck, Bayer and Aegerion, is on the SAB of Catabasis, Regeneron Genetics Center, Merck and Celera, has equity in San Therapeutics and Catabasis, and performs consulting for Novartis, Aegerion, Bristol Myers Squibb, Sanofi, AstraZeneca and Alnylam. P. Sever has received research awards from Pfizer. A. Malarstig and M.U.-N. are full-time employees of Pfizer. D.F.R. and M. Hoek are full-time employees of Merck. M.J.C. is Chief Scientist for Genomics England, a UK government company. The authors declare no other competing financial interests.
Full Text: View/download PDF

33. Defining the role of common variation in the genomic and biological architecture of adult human height

Author: Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, Bennett, Aj, Berne, C, Blüher, M, Bolton, Jl, Böttcher, Y, Boyd, Ha, Bruinenberg, M, Buckley, Bm, Buyske, S, Caspersen, Ih, Chines, Ps, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, Ew, De Jong PA, Deelen, J, Delgado, G, Denny, Jc, Dhonukshe Rutten, R, Dimitriou, M, Doney, As, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, Me, Geller, F, Giedraitis, V, Go, As, Grallert, H, Grammer, Tb, Gräßler, J, Grönberg, H, de Groot LC, Groves, Cj, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, Ca, Hassinen, M, Hayward, C, Heard Costa NL, Helmer, Q, Hemani, G, Henders, Ak, Hillege, Hl, Hlatky, Ma, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat JJ, Illig, T, Isaacs, A, James, Al, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, An, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, Pk, Mahajan, A, Maillard, M, Mcardle, Wl, Mckenzie, Ca, Mclachlan, S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, Workalemahu, T, Zhao, J, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Fraser, R, Goel, A, Gong, J, Justice, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Lui, J, Mangino, M, Leach, I, Medina Gomez, C, Nalls, M, Nyholt, D, Palmer, C, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, J, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, Van Der Laan, S, Van Setten, J, Van Vliet Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Bolton, J, Böttcher, Y, Boyd, H, Bruinenberg, M, Buckley, B, Buyske, S, Caspersen, I, Chines, P, Clarke, R, Claudi Boehm, S, Cooper, M, Daw, E, De Jong, P, Deelen, J, Delgado, G, Denny, J, Dhonukshe Rutten, R, Dimitriou, M, Doney, A, Dörr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, M, Geller, F, Giedraitis, V, Go, A, Grallert, H, Grammer, T, Gräßler, J, Grönberg, H, De Groot, L, Groves, C, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, C, Hassinen, M, Hayward, C, Heard Costa, N, Helmer, Q, Hemani, G, Henders, A, Hillege, H, Hlatky, M, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing Duistermaat, J, Illig, T, Isaacs, A, James, A, Jeff, J, Johansen, B, Johansson, Å, Jolley, J, Juliusdottir, T, Junttila, J, Kho, A, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, P, Mahajan, A, Maillard, M, Mcardle, W, Mckenzie, C, Mclachlan, S, Mclaren, P, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, K, Morken, M, Müller, G, Müller Nurasyid, M, Musk, A, Narisu, N, Nauck, M, Nolte, I, Nöthen, M, Oozageer, L, Pilz, S, Rayner, N, Renstrom, F, Robertson, N, Rose, L, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Schunkert, H, Scott, R, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, J, Smith, A, Smolonska, J, Stanton, A, Stirrups, K, Stott, D, Stringham, H, Sundström, J, Swertz, M, Syvänen, A, Tayo, B, Thorleifsson, G, Tyrer, J, Van Dijk, S, Van Schoor, N, Van Der Velde, N, Van Heemst, D, Van Oort, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Waldenberger, M, Wennauer, R, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Bergmann, S, Biffar, R, Blangero, J, Boomsma, D, Bornstein, S, Bovet, P, Brambilla, P, Brown, M, Campbell, H, Caulfield, M, Chakravarti, A, Collins, R, Collins, F, Crawford, D, Cupples, L, Danesh, J, De Faire, U, Den Ruijter, H, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Ford, I, Forouhi, N, Forrester, T, Gansevoort, R, Gejman, P, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, D, Hall, A, Harris, T, Hattersley, A, Heath, A, Hengstenberg, C, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Jacobs, K, Jarvelin, M, Jousilahti, P, Jula, A, Kaprio, J, Kastelein, J, Kayser, M, Kee, F, Keinanen Kiukaanniemi, S, Kiemeney, L, Kooner, J, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, P, Männistö, S, Manunta, P, Marette, A, Matise, T, Mcknight, B, Meitinger, T, Moll, F, Montgomery, G, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Ouwehand, W, Pasterkamp, G, Peters, A, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schwarz, P, Sebert, S, Sever, P, Shuldiner, A, Sinisalo, J, Steinthorsdottir, V, Stolk, R, Tardif, J, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, De Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hayes, M, Hui, J, Hunter, D, Hveem, K, Jukema, J, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, März, W, Melbye, M, Moebus, S, Munroe, P, Njølstad, I, Oostra, B, Pedersen, N, Perola, M, Pérusse, L, Peters, U, Powell, J, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, P, Rivadeneira, F, Rotter, J, Saaristo, T, Saleheen, D, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, Van Der Harst, P, Völzke, H, Walker, M, Wareham, N, Watkins, H, Wichmann, H, Wilson, J, Zanen, P, Deloukas, P, Heid, I, Lindgren, C, Mohlke, K, Speliotes, E, Thorsteinsdottir, U, Barroso, I, Fox, C, North, K, Strachan, D, Beckmann, J, Berndt, S, Boehnke, M, Borecki, I, Mccarthy, M, Metspalu, A, Stefansson, K, Uitterlinden, A, Van Duijn, C, Franke, L, Willer, C, Price, A, Lettre, G, Loos, R, Weedon, M, Ingelsson, E, O'Connell, J, Abecasis, G, Chasman, D, Goddard, M, Visscher, P, Hirschhorn, J, Frayling, T, Medical Research Council (MRC), APH - Amsterdam Public Health, AMS - Amsterdam Movement Sciences, Geriatrics, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Genomics (eMEMERGEGE) Consortium, MIGen Consortium, PAGEGE Consortium, LifeLines Cohort Study, Electronic Medical, Records, McCarty, CA., Starren, J., Peissig, P., Berg, R., Rasmussen, L., Linneman, J., Miller, A., Choudary, V., Chen, L., Waudby, C., Kitchner, T., Reeser, J., Fost, N., Ritchie, M., Wilke, RA., Chisholm, RL., Avila, PC., Greenland, P., Hayes, M., Kho, A., Kibbe, WA., Lemke, AA., Lowe, WL., Smith, ME., Wolf, WA., Pacheco, JA., Thompson, WK., Humowiecki, J., Law, M., Chute, C., Kullo, I., Koenig, B., de Andrade, M., Bielinski, S., Pathak, J., Savova, G., Wu, J., Henriksen, J., Ding, K., Hart, L., Palbicki, J., Larson, EB., Newton, K., Ludman, E., Spangler, L., Hart, G., Carrell, D., Jarvik, G., Crane, P., Burke, W., Fullerton, SM., Trinidad, SB., Carlson, C., Hutchinson, F., McDavid, A., Roden, DM., Clayton, E., Haines, JL., Masys, DR., Churchill, LR., Cornfield, D., Crawford, D., Darbar, D., Denny, JC., Malin, BA., Ritchie, MD., Schildcrout, JS., Xu, H., Ramirez, AH., Basford, M., Pulley, J., Alizadeh, B., de Boer RA., Boezen, HM., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, HL., van der Klauw MM., Navis, G., Ormel, J., Postma, DS., Rosmalen, JG., Slaets, JP., Snieder, H., Stolk, RP., Wolffenbuttel, BH., Wijmenga, C., Kathiresan, S., Voight, BF., Purcell, S., Musunuru, K., Ardissino, D., Mannucci, PM., Anand, S., Engert, JC., Samani, NJ., Schunkert, H., Erdmann, J., Reilly, MP., Rader, DJ., Morgan, T., Spertus, JA., Stoll, M., Girelli, D., McKeown, PP., Patterson, CC., Siscovick, DS., O'Donnell, CJ., Elosua, R., Peltonen, L., Salomaa, V., Schwartz, SM., Melander, O., Altshuler, D., 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., Subirana, I., Sala, J., Ramos, R., Meigs, JB., Williams, G., Nathan, DM., MacRae, CA., Havulinna, AS., Berglund, G., Voight, B., Hirschhorn, JN., Asselta, R., Duga, S., Spreafico, M., Daly, MJ., Nemesh, J., Korn, JM., McCarroll, SA., Surti, A., Guiducci, C., Gianniny, L., Mirel, D., Parkin, M., Burtt, N., Gabriel, SB., Thompson, JR., Braund, PS., Wright, BJ., Balmforth, AJ., Ball, SG., Hall, AS., Schunkert, I., Linsel-Nitschke, P., Lieb, W., Ziegler, A., König, IR., Hengstenberg, C., Fischer, M., Stark, K., Grosshennig, A., Preuss, M., Wichmann, HE., Schreiber, S., Ouwehand, W., Deloukas, P., Scholz, M., Cambien, F., Goodall, A., Li, M., Chen, Z., Wilensky, R., Matthai, W., Qasim, A., 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., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING DUISTERMAAT, Jj, James, Al, Johansson, A, Kho, An, Magnusson, Pk, Mcardle, Wl, Mckenzie, Ca, Mclaren, Pj, Monda, Kl, Morken, Ma, MÜLLER NURASYID, M, Musk, Aw, Nolte, Im, Nöthen, Mm, Rayner, Nw, Robertson, Nr, Rose, Lm, Schumacher, Fr, Scott, Ra, Smit, Jh, Smith, Av, Stanton, Av, Stott, Dj, Stringham, Hm, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Tyrer, Jp, VAN DIJK, S, VAN SCHOOR, Nm, VAN DER VELDE, N, VAN HEEMST, D, VAN OORT, Fv, Vermeulen, Sh, Vonk, Jm, Waite, Ll, Wilkens, Lr, Wojczynski, Mk, Wright, Af, Bakker, Sj, Bergman, Rn, Boomsma, Di, Bornstein, Sr, Brown, Mj, Caulfield, Mj, Crawford, Dc, Cupples, La, DE FAIRE, U, DEN RUIJTER, Hm, Eriksson, Jg, Forouhi, Ng, Gansevoort, Rt, Gejman, Pv, Haas, Dw, Harris, Tb, Hattersley, At, Heath, Ac, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hovingh, Gk, Humphries, Se, Hunt, Sc, Jacobs, Kb, Jarvelin, Mr, Jula, Am, Kastelein, Jj, KEINANEN KIUKAANNIEMI, Sm, Kiemeney, La, Kraja, At, Lakka, Ta, LE MARCHAND, L, Madden, Pa, Manunta, Paolo, Matise, Tc, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.
Subjects: Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, Medizin, Genome-wide association study, Adult, Analysis of Variance, Body Height/genetics, European Continental Ancestry Group/genetics, Genetic Variation/genetics, Genetics, Population, Genome-Wide Association Study/methods, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide/genetics, heritability, 0302 clinical medicine, Genome-wide, SNPS, snps, Genetics & Heredity, ddc:616, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, variants, GENETIC-VARIATION, Biological Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], body height, genetic-variation, Life Sciences & Biomedicine, Single Nucleotide/genetics, Human, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, NO, complex traits, 03 medical and health sciences, Genetic variation, heritability, adult, height, Polymorphism, Human height, PAGEGE Consortium, education, Gene, VLAG, 030304 developmental biology, Global Nutrition, Wereldvoeding, genome-wide association study, Science & Technology, Whites, Oligonucleotide Array Sequence Analysi, MUTATIONS, COMPLEX TRAITS, ta1184, Klinisk medicin, population genetics, Genetic Variation, Heritability, ta3121, mutations, Genetic architecture, Body Height, genetic variation, MIGen Consortium, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Clinical Medicine, 030217 neurology & neurosurgery, height, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract: Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
Published: 2014
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

33 results on '"Doney, A.S.F."'

1. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

2. The cost of cerebral ischaemia

3. Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability (Nature Communications, (2021), 12, 1, (24), 10.1038/s41467-020-19366-9)

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

5. Long-term cardiovascular safety of febuxostat compared with allopurinol in patients with gout (FAST): a multicentre, prospective, randomised, open-label, non-inferiority trial

6. Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

7. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

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

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

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

11. Parental origin of sequence variants associated with complex diseases

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

13. Investigating Real-World Clopidogrel Pharmacogenetics in Stroke Using a Bioresource Linked to Electronic Medical Records

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

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

16. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

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

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

19. Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci

20. Pharmacogenetic meta-analysis of genome-wide association studies of LDL cholesterol response to statins

21. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

22. Common variants in mendelian kidney disease genes and their association with renal function

23. Genetic Loci for Retinal Arteriolar Microcirculation

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

25. Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): A meta-analysis of genome-wide association studies

26. Genome-wide association and functional follow-up reveals new loci for kidney function

27. Genetic association analysis of LARS2 with type 2 diabetes

28. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

29. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

30. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

31. Variants in MTNR1B influence fasting glucose levels

32. Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

33. Defining the role of common variation in the genomic and biological architecture of adult human height

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

33 results on '"Doney, A.S.F."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources