المؤلفون: Wood, A.R. (Andrew), Esko, T. (Tõnu), Yang, J. (Jian), Vedantam, S. (Sailaja), Pers, T.H. (Tune), Gustafsson, S. (Stefan), Chu, A.Y. (Audrey Y), Estrada Gil, K. (Karol), Luan, J., Kutalik, Z., Amin, N. (Najaf), Buchkovich, M.L. (Martin), Croteau-Chonka, D.C. (Damien), Day, F.R. (Felix), Duan, Y. (Yanan), Fall, M. (Magnus), Fehrmann, R.S.N. (Rudolf), Ferreira, T. (Teresa), Jackson, A.U. (Anne), Karjalainen, J. (Juha), Lo, K.S. (Ken Sin), Locke, A. (Adam), Mägi, R. (Reedik), Mihailov, E. (Evelin), Porcu, E. (Eleonora), Randall, J.C. (Joshua), Scherag, A. (Andre), Vinkhuyzen, A.A.E. (Anna A.), Westra, H.J. (Harm-Jan), Winkler, T.W. (Thomas W.), Workalemahu, T. (Tsegaselassie), Zhao, J.H. (Jing Hua), Absher, D. (Devin), Albrecht, E. (Eva), Baron, J. (Jeffrey), Beekman, M. (Marian), Demirkan, A. (Ayşe), Ehret, G.B. (Georg), Feenstra, B., Feitosa, M.F. (Mary Furlan), Fischer, K. (Krista), Fraser, R.M. (Ross), Goel, A. (Anuj), Gong, J. (Jian), Justice, A.E. (Anne), Kanoni, S. (Stavroula), Kleber, M.E. (Marcus), Kristiansson, K. (Kati), Lim, U. (Unhee), Lotay, V. (Vaneet), Lui, J.C. (Julian C), Mangino, M. (Massimo), Leach, I.M. (Irene Mateo), Medina-Gomez, M.C. (Carolina), Nalls, M.A. (Michael), Dimas, A.S. (Antigone), Palmer, C. (Cameron), Pasko, D. (Dorota), Pechlivanis, S. (Sonali), Prokopenko, I. (Inga), Ried, J.S. (Janina), Ripke, S. (Stephan), Shungin, D. (Dmitry), Stancáková, A. (Alena), Strawbridge, R.J. (Rona), Sung, Y.J. (Yun Ju), Tanaka, T. (Toshiko), Teumer, A. (Alexander), Trompet, S. (Stella), Van Der Laan, S.W. (Sander W.), Setten, J. (Jessica) van, Vliet-Ostaptchouk, J.V. (Jana) van, Wang, Z. (Zhaoming), Yengo, L. (Loic), Zhang, W. (Weihua), Afzal, U. (Uzma), 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), Bolton, J.L. (Jennifer), Böttcher, Y. (Yvonne), Boyd, H.A., Bruinenberg, M. (M.), Buckley, B.M. (Brendan M.), Buyske, S. (Steven), Caspersen, I.H. (Ida H.), Chines, P.S. (Peter), Clarke, R. (Robert), Claudi-Boehm, S. (Simone), Cooper, M.N. (Matthew), Daw, E.W. (E Warwick), De Jong, P.A. (Pim A), Deelen, J. (Joris), Delgado, G., Denny, J.C. (Josh C), Dhonukshe-Rutten, R.A.M. (Rosalie), Dimitriou, M. (Maria), Doney, A.S.F. (Alex), Dörr, M. (Marcus), Eklund, N. (Niina), Eury, E. (Elodie), Folkersen, L. (Lasse), Garcia, M. (Melissa), Geller, F. (Frank), Giedraitis, V. (Vilmantas), Go, A.T.J.I. (Attie), Grallert, H. (Harald), Grammer, T.B. (Tanja B), Gräßler, J. (Jürgen), Grönberg, H. (Henrik), Groot, L.C.P.G.M. (Lisette) de, Groves, C.J. (Christopher J.), Haessler, J. (Jeff), Hall, P. (Per), Haller, T. (Toomas), Hallmans, G. (Göran), Hannemann, M. (Mario), Hartman, C.A. (Catharina), Hassinen, M. (Maija), Hayward, C. (Caroline), Heard-Costa, N.L. (Nancy), Helmer, Q. (Quinta), Hemani, G., Henders, A.K. (Anjali), Hillege, H.L. (Hans), Hlatky, M.A. (Mark), Hoffmann, W. (Wolfgang), Hoffmann, P. (Per), Holmen, O.L. (Oddgeir), Houwing-Duistermaat, J.J. (Jeanine), Illig, T. (Thomas), Isaacs, A. (Aaron), James, A.L. (Alan), Jeff, J. (Janina), Johansen, B. (Berit), Johansson, A. (Åsa), Jolley, G.J. (Jason), Juliusdottir, T. (Thorhildur), Junttila, M.J. (Juhani), Kho, M.M.L. (Marcia), Kinnunen, L. (Leena), Klopp, N. (Norman), Kocher, T., Kratzer, W. (Wolfgang), Lichtner, P. (Peter), Lind, L. (Lars), Lindström, J. (Jaana), Lobbens, S. (Stéphane), Lorentzon, M. (Mattias), Lu, Y. (Yingchang), Lyssenko, V. (Valeriya), Magnusson, P.K. (Patrik), Mahajan, A. (Anubha), Maillard, M. (Marc), McArdle, W.L. (Wendy), McKenzie, C.A. (Colin A.), McLachlan, S. (Stela), McLaren, P.J. (Paul J), Menni, C. (Cristina), Merger, S. (Sigrun), Milani, L. (Lili), Moayyeri, A. (Alireza), Monda, K.L. (Keri), Morken, M.A. (Mario), Müller, G. (Gabriele), Müller-Nurasyid, M. (Martina), Musk, A.W. (Arthur), Narisu, N. (Narisu), Nauck, M. (Matthias), Nolte, I.M. (Ilja M.), Nöthen, M.M. (Markus), Oozageer, L. (Laticia), Pilz, S. (Stefan), Rayner, N.W. (Nigel William), Renström, F. (Frida), Robertson, N.R. (Neil R.), Rose, L.M. (Lynda M.), Roussel, R. (Ronan), Sanna, S. (Serena), Scharnagl, H. (Hubert), Scholtens, S. (Salome), Schumacher, F.R. (Fredrick R), Schunkert, H. (Heribert), Scott, R.A. (Robert), Sehmi, J.S. (Joban), Seufferlein, T. (Thomas), Shi, J. (Jianxin), Silventoinen, K. (Karri), Smit, J.H. (Johannes), Smith, A.V. (Davey), Smolonska, J. (Joanna), Stanton, A. (Alice), Stirrups, K. (Kathy), Stott, D.J.M. (David), Stringham, H.M. (Heather), Sundstrom, J. (Johan), Swertz, M. (Morris), Syvanen, A.C., Tayo, B. (Bamidele), Thorleifsson, G. (Gudmar), Tyrer, J.P. (Jonathan), Van Dijk, S. (Suzanne), Schoor, N.M. (Natasja) van, Velde, N. (Nathalie) van der, Heemst, D. (Diana) van, Van Oort, F.V.A. (Floor V A), Vermeulen, S.H.H.M. (Sita), Verweij, N. (Niek), Vonk, J.M. (Judith M), Waite, L. (Lindsay), Waldenberger, M. (Melanie), Wennauer, R. (Roman), Wilkens, L.R. (Lynne R.), Willenborg, C. (Christina), Wilsgaard, T. (Tom), Wojczynski, M.K. (Mary ), Wong, A. (Andrew), Wright, A. (Alan), Zhang, Q. (Qunyuan), Arveiler, D. (Dominique), Bakker, S.J.L. (Stephan), Beilby, J. (John), Bergman, R.N. (Richard), Bergmann, S.M. (Sven), Biffar, R., Blangero, J. (John), Boomsma, D.I. (Dorret), Bornstein, S.R. (Stefan R.), Bovet, P. (Pascal), Brambilla, P. (Paolo), Brown, M.J. (Morris), Campbell, H. (Harry), Caulfield, M. (Mark), Chakravarti, A. (Aravinda), Collins, F.S. (Francis), Crawford, D.C. (Dana), Cupples, L.A. (Adrienne), Danesh, J. (John), Faire, U. (Ulf) de, Ruijter, H.M. (Hester ) den, Erbel, R. (Raimund), Erdmann, J. (Jeanette), Eriksson, J., Farrall, M. (Martin), Ferrannini, E. (Ele), Ferrieres, J. (Jean), Ford, I., Forouhi, N.G. (Nita), Forrester, T. (Terrence), Gansevoort, R.T. (Ron), Gejman, P.V. (Pablo), Gieger, C. (Christian), Golay, A. (Alain), Gottesman, R.F. (Rebecca), Gudnason, V. (Vilmundur), Gyllensten, U. (Ulf), Haas, D.W. (David W), Hall, A.S. (Alistair), Harris, T.B. (Tamara), Hattersley, A.T. (Andrew), Heath, A.C. (Andrew C), Hengstenberg, C. (Christian), Hicks, A.A. (Andrew), Hindorff, L.A. (Lucia A), Hingorani, A. (Aroon), Hofman, A. (Albert), Hovingh, G.K. (Kees), Humphries, S.E. (Steve E.), Hunt, S.C. (Steven), Hypponen, E. (Elina), Jacobs, K.B. (Kevin), Jarvelin, M.-R. (Marjo-Riitta), Jousilahti, P. (Pekka), Jula, A. (Antti), Kaprio, J. (Jaakko), Kastelein, J.J.P. (John), Kayser, M.H. (Manfred), Kee, F. (Frank), Keinanen-Kiukaanniemi, S. (Sirkka), Kiemeney, L.A.L.M. (Bart), Kooner, J.S. (Jaspal S.), Kooperberg, C. (Charles), Koskinen, S. (Seppo), Kovacs, P. (Peter), Kraja, A. (Aldi), Kumari, M. (Meena), Kuusisto, J. (Johanna), Lakka, T.A. (Timo), Langenberg, C. (Claudia), Le Marchand, L. (Loic), Lehtimäki, T. (Terho), Lupoli, S. (Sara), Madden, P.A., Männistö, S. (Satu), Manunta, P. (Paolo), Marette, A. (Andre'), Matise, T.C. (Tara C.), McKnight, B. (Barbara), Meitinger, T. (Thomas), Moll, F.L. (Frans), Montgomery, G.W. (Grant W.), Morris, A.D. (Andrew), Morris, A.P. (Andrew), Murray, J.C. (Jeffrey), Nelis, M. (Mari), Ohlsson, C. (Claes), Oldehinkel, A.J. (Albertine), Ong, K.K. (Ken K.), Ouwehand, W.H. (Willem), Pasterkamp, G. (Gerard), Peters, A. (Annette), Pramstaller, P.P. (Peter Paul), Price, J.F. (Jackie F.), Qi, L. (Lu), Raitakari, O. (Olli), Rankinen, T. (Tuomo), Rao, D.C. (Dabeeru C.), Rice, T.K. (Treva K.), 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.), Sebert, S. (Sylvain), Sever, P. (Peter), Shuldiner, A.R. (Alan), Sinisalo, J. (Juha), Steinthorsdottir, V. (Valgerdur), Stolk, R.P., Tardif, J.-C. (Jean-Claude), Tönjes, A. (Anke), Tremblay, A. (Angelo), Tremoli, E. (Elena), Virtamo, J. (Jarmo), Vohl, M.-C. (Marie-Claude), Amouyel, P. (Philippe), Asselbergs, F.W. (Folkert W.), Assimes, T.L. (Themistocles), Bochud, M. (Murielle), Boehm, B.O. (Bernhard), Boerwinkle, E.A. (Eric), Bottinger, E.P. (Erwin P.), Bouchard, C. (Claude), Cauchi, S. (Stéphane), Chambers, J.C. (John C.), Chanock, S.J. (Stephen), Cooper, R.S. (Richard S.), Bakker, P.I.W. (Paul) de, Dedoussis, G.V. (George), Ferrucci, L. (Luigi), Franks, P.W., Froguel, P. (Philippe), Groop, L. (Leif), Haiman, C.A. (Christopher), Hamsten, A. (Anders), Hayes, M.G. (M. Geoffrey), Hui, J. (Jennie), Hunter, D. (David), Hveem, K. (Kristian), Jukema, J.W. (Jan Wouter), Kaplan, R.C. (Robert), Kivimaki, M. (Mika), Kuh, D. (Diana), Laakso, M. (Markku), Liu, Y. (YongMei), Martin, N.G. (Nicholas), März, W. (Winfried), Melbye, M. (Mads), Moebus, S. (Susanne), 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), Powell, J.E. (Joseph), Power, C. (Christine), Quertermous, T. (Thomas), Rauramaa, R. (Rainer), Reinmaa, E. (Eva), Ridker, P.M. (Paul), Rivadeneira Ramirez, F. (Fernando), Rotter, J.I. (Jerome I.), Saaristo, T. (Timo), Saleheen, D., Schlessinger, D. (David), Slagboom, P.E. (Eline), Snieder, H. (Harold), Spector, T.D. (Timothy), Strauch, K. (Konstantin), Stumvoll, M. (Michael), Tuomilehto, J. (Jaakko), Uusitupa, M. (Matti), Harst, P. (Pim) van der, Völzke, H. (Henry), Walker, M. (Mark), Wareham, N.J. (Nick), Watkins, H. (Hugh), Wichmann, H.E. (Heinz Erich), Wilson, J.F. (James F), Zanen, P. (Pieter), Deloukas, P. (Panagiotis), Heid, I.M. (Iris), Lindgren, C.M. (Cecilia), Mohlke, K.L. (Karen), Speliotes, E.K. (Elizabeth), Thorsteinsdottir, U. (Unnur), Barroso, I.E. (Inês), Fox, C.S. (Caroline S.), North, K.E. (Kari), Strachan, D.P. (David P.), Beckmann, J.S. (Jacques), Berndt, S.I. (Sonja), Boehnke, M. (Michael), Borecki, I.B. (Ingrid), McCarthy, M.I. (Mark), Metspalu, A. (Andres), Zwart, J-A. (John-Anker), Uitterlinden, A.G. (André), Duijn, C.M. (Cornelia) van, Franke, L. (Lude), Willer, C.J. (Cristen), Price, A. (Alkes), Lettre, G. (Guillaume), Loos, R.J.F. (Ruth), Weedon, M.N. (Michael), Ingelsson, E. (Erik), O´Connell, J.R., Abecasis, G.R. (Gonçalo), Chasman, D.I. (Daniel), Anderson, D. (Denise), Goddard, M.E. (Michael), Visscher, P.M. (Peter), Hirschhorn, J.N. (Joel), Frayling, T.M. (Timothy)

الوصف: 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 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% 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/I 2-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 var

العلاقة: http://repub.eur.nl/pub/86022Test; urn:hdl:1765/86022

الإتاحة: https://doi.org/10.1038/ng.3097Test
http://repub.eur.nl/pub/86022Test

المؤلفون: Ehret, G.B. (Georg), Munroe, P. (Patricia), Rice, K.M. (Kenneth), Bochud, M. (Murielle), Johnson, A.D. (Andrew), Chasman, D.I. (Daniel), Smith, A.V. (Albert Vernon), Tobin, M.D. (Martin), Verwoert, G.C. (Germaine), Hwang, S.J., Pihur, V. (Vasyl), Vollenweider, P. (Peter), O'Reilly, P.F. (Paul), Amin, N. (Najaf), Bragg-Gresham, J.L. (Jennifer L.), Teumer, A. (Alexander), Glazer, N.L. (Nicole), Launer, L.J. (Lenore), Zhao, J.H. (Jing Hua), Aulchenko, Y.S. (Yurii), Heath, S.C. (Simon), Sõber, S. (Siim), Parsa, A. (Afshin), Luan, J., Arora, P. (Pankaj), Dehghan, A. (Abbas), Zhang, F. (Feng), Lucas, G. (Gavin), Hicks, A.A. (Andrew), Jackson, A.U. (Anne), Peden, J. (John), Tanaka, T. (Toshiko), Wild, S.H. (Sarah), Rudan, I. (Igor), Igl, W. (Wilmar), Milaneschi, Y. (Yuri), Parker, A.N. (Alex), Fava, C. (Cristiano), Chambers, J.C. (John), Fox, E.R. (Ervin), Kumari, M. (Meena), Jin Go, M. (Min), Harst, P. (Pim) van der, Kao, W.-H.L. (Wen-Hong Linda), Sjögren, M. (Marketa), Vinay, D.G., Alexander, M. (Myriam), Tabara, Y. (Yasuharu), Shaw-Hawkins, S. (Sue), Whincup, P.H. (Peter), Liu, Y. (YongMei), Shi, G. (Gang), Kuusisto, J. (Johanna), Tayo, B. (Bamidele), Seielstad, M. (Mark), Sim, X. (Xueling), Hoang Nguyen, K.-D., Lehtimäki, T. (Terho), Matullo, G. (Giuseppe), Wu, Y. (Ying), Gaunt, T.R. (Tom), Onland-Moret, N.C. (Charlotte), Cooper, M.N. (Matthew), Platou, C. (Carl), Org, E. (Elin), Hardy, R. (Rebecca), Dahgam, S. (Santosh), Palmen, J. (Jutta), Vitart, V. (Veronique), Braund, P.S. (Peter), Kuznetsova, T. (Tatiana), Uiterwaal, C.S.P.M. (Cuno), Adeyemo, A. (Adebowale), Palmas, W. (Walter), Campbell, H. (Harry), Ludwig, B. (Barbara), Tomaszewski, M., Tzoulaki, I., Palmer, N.D. (Nicholette), Aspelund, T. (Thor), Garcia, M. (Melissa), Chang, Y.-P.C. (Yen-Pei), O´Connell, J.R., Steinle, N.I. (Nanette), Grobbee, D.E. (Diederick), Arking, D.E. (Dan), Kardia, S.L. (Sharon), Morrison, A.C. (Alanna), Hernandez, D.G. (Dena), Najjar, S.S. (Samer), McArdle, W.L. (Wendy), Hadley, D. (David), Brown, M.J. (Morris), Connell, J. (John), Hingorani, A. (Aroon), Day, I.N.M. (Ian), Lawlor, D.A. (Debbie), Beilby, J.P. (John), Lawrence, R.W. (Robert), Clarke, R., Hopewell, J., Ongen, H. (Halit), Dreisbach, A.W. (Albert), Li, Y. (Yali), Hunter Young, J., Bis, J.C. (Joshua), Kähönen, M. (Mika), Viikari, J. (Jorma), Lee, N.R. (Nanette), Chen, M-H. (Ming-Huei), Olden, M. (Matthias), Pattaro, C. (Cristian), Hoffman Bolton, J.A. (Judith), Köttgen, A. (Anna), Bergmann, S.M. (Sven), Mooser, V. (Vincent), Chaturvedi, N. (Nish), Frayling, T.M. (Timothy), Islam, M. (Muhammad), Jafar, T.H. (Tazeen), Kulkarni, S.R. (Smita), Bornstein, S.R. (Stefan), Gräßler, J. (Jürgen), Groop, L. (Leif), Voight, B.F. (Benjamin), Kettunen, J. (Johannes), Howard, P. (Philip), Taylor, A. (Andrew), Guarrera, S. (Simonetta), Ricceri, F. (Fulvio), Emilsson, V. (Valur), Plump, A.S. (Andrew), Khaw, K-T. (Kay-Tee), Weder, A.B. (Alan), Hunt, S.C. (Steven), Sun, Y.V. (Yan), Bergman, R.N. (Richard), Collins, F.S. (Francis), Bonnycastle, L.L. (Lori), Scott, L.J. (Laura), Stringham, H.M. (Heather), Peltonen, L. (Leena Johanna), Perola, M. (Markus), Vartiainen, E. (Erkki), Brand, S.-M., Staessen, J.A. (Jan), Wang, Y.A. (Ying), Burton, P.R. (Paul), Soler Artigas, M. (Maria), Dong, Y. (Yanbin), Snieder, H. (Harold), Zhu, H. (Haidong), Lohman, K. (Kurt), Rudock, M.E. (Megan), Heckbert, S.R. (Susan), Wiggins, K.L. (Kerri), Doumatey, A. (Ayo), Shriner, D. (Daniel), Veldre, G. (Gudrun), Viigimaa, M. (Margus), Kinra, S. (Sanjay), Prabhakaran, D. (Dorairaj), Tripathy, V. (Vikal), Langefeld, C.D. (Carl), Rosengren, A. (Annika), Thelle, D.S. (Dag), Corsi, A.M. (Anna Maria), Singleton, A. (Andrew), Forrester, T. (Terrence), Hilton, G. (Gina), McKenzie, C.A. (Colin), Salako, T. (Tunde), Iwai, N. (Naoharu), Kita, Y. (Yoshikuni), Ogihara, T. (Toshio), Ohkubo, T. (Takayoshi), Okamura, T. (Tomonori), Ueshima, H. (Hirotsugu), Umemura, S. (Satoshi), Eyheramendy, S. (Susana), Meitinger, T. (Thomas), Wichmann, H.E. (Heinz Erich), Shin Cho, Y. (Yoon), Kim, H.-L., Sehmi, J.S. (Joban), Hedblad, B. (Bo), Nilsson, P. (Peter), Davey-Smith, G. (George), Wong, A. (Andrew), Narisu, N. (Narisu), Stancáková, A. (Alena), Raffel, L.J. (Leslie), Yao, J. (Jie), Kathiresan, S. (Sekar), O'Donnell, C.J. (Christopher), Schwartz, S.M. (Stephen), Ikram, M.A. (Arfan), Longstreth Jr, W.T., Mosley, T.H. (Thomas), Seshadri, S. (Sudha), Shrine, N.R.G. (Nick), Wain, L.V. (Louise), Morken, M.A. (Mario), Swift, A.J. (Amy), Laitinen, J. (Jaana), Prokopenko, I. (Inga), Zitting, P. (Paavo), Humphries, S.E. (Steve), Danesh, J. (John), Rasheed, A. (Asif), Goel, A. (Anuj), Hamsten, A. (Anders), Watkins, H. (Hugh), Gilst, W.H. (Wiek) van, Janipalli, C.S. (Charles), Radha Mani, K., Yajnik, C. (Chittaranjan), Hofman, A. (Albert), Mattace Raso, F.U.S. (Francesco), Oostra, B.A. (Ben), Demirkan, A. (Ayşe), Isaacs, A.J. (Aaron), Rivadeneira Ramirez, F. (Fernando), Lakatta, E. (Edward), Orrù, M. (Marco), Scuteri, A. (Angelo), Ala-Korpela, M. (Mika), Kangas, A.J. (Antti), Lyytikäinen, L.-P. (Leo-Pekka), Soininen, P. (Pasi), Tukiainen, T. (Taru), Würtz, P. (Peter), Twee-Hee Ong, R. (Rick), Dörr, M. (Marcus), Kroemer, H.K. (Heyo), Völker, U. (Uwe), Völzke, H. (Henry), Galan, P. (Pilar), Hercberg, S. (Serge), Lathrop, G.M. (Mark), Zelenika, D. (Diana), Deloukas, P. (Panagiotis), Mangino, M. (Massimo), Spector, T.D. (Timothy), Zhai, G. (Guangju), Meschia, J.F. (James F.), Nalls, M.A. (Michael), Sharma, P. (Pankaj), Terzic, J. (Janos), Kranthi Kumar, M.V., Denniff, M. (Matthew), Zukowska-Szczechowska, E. (Ewa), Wagenknecht, L.E. (Lynne), Fowkes, F.G.R. (Gerald), Charchar, F.J. (Fadi), Schwarz, P.E.H. (Peter), Hayward, C. (Caroline), Guo, X. (Xiuqing), Rotimi, C. (Charles), Bots, M.L. (Michiel), Samani, N.J. (Nilesh), Polasek, O. (Ozren), Talmud, P.J. (Philippa), Nyberg, F. (Fredrik), Kuh, D. (Diana), Laan, M. (Maris), Hveem, K. (Kristian), Schouw, Y.T. 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المصدر: Nature: international weekly journal of science vol. 478 no. 7367, pp. 103-109

الوصف: Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140mmg Hg systolic blood pressure ≥90mmg Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3 GUCY1B3, NPR3 C5orf23, ADM, FURIN FES, GOSR2, GNAS EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 geno

العلاقة: http://repub.eur.nl/pub/33262Test; urn:hdl:1765/33262

الإتاحة: https://doi.org/10.1038/nature10405Test
http://repub.eur.nl/pub/33262Test

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المصدر: Diabetes vol. 60 no. 10, pp. 2624-2634

الوصف: 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.

وصف الملف: application/pdf

العلاقة: https://repub.eur.nl/pub/94603Test; urn:hdl:1765/94603

الإتاحة: https://doi.org/10.2337/db11-0415Test
https://repub.eur.nl/pub/94603Test