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Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Tuesday,2012-11-06 12:26 America/Los_Angeles — eenright
TitleNovel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
Publication TypeJournal Article
Year of Publication2012
AuthorsDastani, Z, Hivert, M-F, Timpson, N, Perry, JRB, Yuan, X, Scott, RA, Henneman, P, Heid, IM, Kizer, JR, Lyytikäinen, L-P, Fuchsberger, C, Tanaka, T, Morris, AP, Small, K, Isaacs, A, Beekman, M, Coassin, S, Lohman, K, Qi, L, Kanoni, S, Pankow, JS, Uh, H-W, Wu, Y, Bidulescu, A, Rasmussen-Torvik, LJ, Greenwood, CMT, Ladouceur, M, Grimsby, J, Manning, AK, Liu, C-T, Kooner, J, Mooser, VE, Vollenweider, P, Kapur, KA, Chambers, J, Wareham, NJ, Langenberg, C, Frants, R, Willems-Vandijk, K, Oostra, BA, Willems, SM, Lamina, C, Winkler, TW, Psaty, BM, Tracy, RP, Brody, J, Chen, I, Viikari, J, Kähönen, M, Pramstaller, PP, Evans, DM, St Pourcain, B, Sattar, N, Wood, AR, Bandinelli, S, Carlson, OD, Egan, JM, Böhringer, S, van Heemst, D, Kedenko, L, Kristiansson, K, Nuotio, M-L, Loo, B-M, Harris, T, Garcia, M, Kanaya, A, Haun, M, Klopp, N, Wichmann, H-E, Deloukas, P, Katsareli, E, Couper, DJ, Duncan, BB, Kloppenburg, M, Adair, LS, Borja, JB, Wilson, JG, Musani, S, Guo, X, Johnson, T, Semple, R, Teslovich, TM, Allison, MA, Redline, S, Buxbaum, SG, Mohlke, KL, Meulenbelt, I, Ballantyne, CM, Dedoussis, GV, Hu, FB, Liu, Y, Paulweber, B, Spector, TD, P Slagboom, E, Ferrucci, L, Jula, A, Perola, M, Raitakari, O, Florez, JC, Salomaa, V, Eriksson, JG, Frayling, TM, Hicks, AA, Lehtimäki, T, Smith, GD, Siscovick, DS, Kronenberg, F, van Duijn, C, Loos, RJF, Waterworth, DM, Meigs, JB, Dupuis, J, J Richards, B, Voight, BF, Scott, LJ, Steinthorsdottir, V, Dina, C, Welch, RP, Zeggini, E, Huth, C, Aulchenko, YS, Thorleifsson, G, McCulloch, LJ, Ferreira, T, Grallert, H, Amin, N, Wu, G, Willer, CJ, Raychaudhuri, S, McCarroll, SA, Hofmann, OM, Segrè, AV, van Hoek, M, Navarro, P, Ardlie, K, Balkau, B, Benediktsson, R, Bennett, AJ, Blagieva, R, Boerwinkle, E, Bonnycastle, LL, Boström, KBengtsson, Bravenboer, B, Bumpstead, S, Burtt, NP, Charpentier, G, Chines, PS, Cornelis, M, Crawford, G, Doney, ASF, Elliott, KS, Elliott, AL, Erdos, MR, Fox, CS, Franklin, CS, Ganser, M, Gieger, C, Grarup, N, Green, T, Griffin, S, Groves, CJ, Guiducci, C, Hadjadj, S, Hassanali, N, Herder, C, Isomaa, B, Jackson, AU, Johnson, PRV, Jørgensen, T, Kao, WHL, Kong, A, Kraft, P, Kuusisto, J, Lauritzen, T, Li, M, Lieverse, A, Lindgren, CM, Lyssenko, V, Marre, M, Meitinger, T, Midthjell, K, Morken, MA, Narisu, N, Nilsson, P, Owen, KR, Payne, F, Petersen, A-K, Platou, C, Proença, C, Prokopenko, I, Rathmann, W, N Rayner, W, Robertson, NR, Rocheleau, G, Roden, M, Sampson, MJ, Saxena, R, Shields, BM, Shrader, P, Sigurdsson, G, Sparsø, T, Strassburger, K, Stringham, HM, Sun, Q, Swift, AJ, Thorand, B, Tichet, J, Tuomi, T, van Dam, RM, van Haeften, TW, van Herpt, T, van Vliet-Ostaptchouk, JV, Walters, BG, Weedon, MN, Wijmenga, C, Witteman, J, Bergman, RN, Cauchi, S, Collins, FS, Gloyn, AL, Gyllensten, U, Hansen, T, Hide, WA, Hitman, GA, Hofman, A, Hunter, DJ, Hveem, K, Laakso, M, Morris, AD, Palmer, CNA, Rudan, I, Sijbrands, E, Stein, LD, Tuomilehto, J, Uitterlinden, A, Walker, M, Watanabe, RM, Abecasis, GR, Boehm, BO, Campbell, H, Daly, MJ, Hattersley, AT, Pedersen, O, Barroso, I, Groop, L, Sladek, R, Thorsteinsdottir, U, Wilson, JF, Illig, T, Froguel, P, van Duijn, CM, Stefansson, K, Altshuler, D, Boehnke, M, McCarthy, MI, Soranzo, N, Wheeler, E, Glazer, NL, Bouatia-Naji, N, Mägi, R, Randall, J, Elliott, P, Rybin, D, Dehghan, A, Hottenga, JJ, Song, K, Goel, A, Lajunen, T, Doney, A, Cavalcanti-Proença, C, Kumari, M, Timpson, NJ, Zabena, C, Ingelsson, E, An, P, O'Connell, J, Luan, J'an, Elliott, A, McCarroll, SA, Roccasecca, RM, Pattou, F, Sethupathy, P, Ariyurek, Y, Barter, P, Beilby, JP, Ben-Shlomo, Y, Bergmann, S, Bochud, M, Bonnefond, A, Borch-Johnsen, K, Böttcher, Y, Brunner, E, Bumpstead, SJ, Chen, Y-DI, Chines, P, Clarke, R, Coin, LJM, Cooper, MN, Crisponi, L, Day, INM, de Geus, EJC, Delplanque, J, Fedson, AC, Fischer-Rosinsky, A, Forouhi, NG, Franzosi, MG, Galan, P, Goodarzi, MO, Graessler, J, Grundy, S, Gwilliam, R, Hallmans, G, Hammond, N, Han, X, Hartikainen, A-L, Hayward, C, Heath, SC, Hercberg, S, Hillman, DR, Hingorani, AD, Hui, J, Hung, J, Kaakinen, M, Kaprio, J, Kesaniemi, AY, Kivimaki, M, Knight, B, Koskinen, S, Kovacs, P, Kyvik, KO, Lathrop, MG, Lawlor, DA, Le Bacquer, O, Lecoeur, C, Li, Y, Mahley, R, Mangino, M, Martínez-Larrad, MT, McAteer, JB, McPherson, R, Meisinger, C, Melzer, D, Meyre, D, Mitchell, BD, Mukherjee, S, Naitza, S, Neville, MJ, Orrù, M, Pakyz, R, Paolisso, G, Pattaro, C, Pearson, D, Peden, JF, Pedersen, NL, Pfeiffer, AFH, Pichler, I, Polasek, O, Posthuma, D, Potter, SC, Pouta, A, Province, MA, Rayner, NW, Rice, K, Ripatti, S, Rivadeneira, F, Rolandsson, O, Sandbaek, A, Sandhu, M, Sanna, S, Sayer, AA, Scheet, P, Seedorf, U, Sharp, SJ, Shields, B, Sigurðsson, G, Sijbrands, EJG, Silveira, A, Simpson, L, Singleton, A, Smith, NL, Sovio, U, Swift, A, Syddall, H, Syvänen, A-C, Tönjes, A, Uitterlinden, AG, van Dijk, KW, Varma, D, Visvikis-Siest, S, Vitart, V, Vogelzangs, N, Waeber, G, Wagner, PJ, Walley, A, Ward, KL, Watkins, H, Wild, SH, Willemsen, G, Witteman, JCM, Yarnell, JWG, Zelenika, D, Zethelius, B, Zhai, G, Zhao, JH, Zillikens, CM, Borecki, IB, Meneton, P, Magnusson, PKE, Nathan, DM, Williams, GH, Silander, K, Bornstein, SR, Schwarz, P, Spranger, J, Karpe, F, Shuldiner, AR, Cooper, C, Serrano-Ríos, M, Lind, L, Palmer, LJ, Hu, FB, Franks, PW, Ebrahim, S, Marmot, M, Kao, LWH, Pramstaller, PP, Wright, AF, Stumvoll, M, Hamsten, A, Buchanan, TA, Valle, TT, Rotter, JI, Penninx, BWJH, Boomsma, DI, Cao, A, Scuteri, A, Schlessinger, D, Uda, M, Ruokonen, A, Jarvelin, M-R, Peltonen, L, Mooser, V, Sladek, R, Musunuru, K, Smith, AV, Edmondson, AC, Stylianou, IM, Koseki, M, Pirruccello, JP, Chasman, DI, Johansen, CT, Fouchier, SW, Peloso, GM, Barbalic, M, Ricketts, SL, Bis, JC, Feitosa, MF, Orho-Melander, M, Melander, O, Li, X, Li, M, Cho, YS, Go, MJ, Kim, YJin, Lee, J-Y, Park, T, Kim, K, Sim, X, Ong, RT-H, Croteau-Chonka, DC, Lange, LA, Smith, JD, Ziegler, A, Zhang, W, Zee, RYL, Whitfield, JB, Thompson, JR, Surakka, I, Spector, TD, Smit, JH, Sinisalo, J, Scott, J, Saharinen, J, Sabatti, C, Rose, LM, Roberts, R, Rieder, M, Parker, AN, Paré, G, O'Donnell, CJ, Nieminen, MS, Nickerson, DA, Montgomery, GW, McArdle, W, Masson, D, Martin, NG, Marroni, F, Lucas, G, Luben, R, Lokki, M-L, Lettre, G, Launer, LJ, Lakatta, EG, Laaksonen, R, Kyvik, KO, König, IR, Khaw, K-T, Kaplan, LM, Johansson, A, A Janssens, CJW, Igl, W, G Hovingh, K, Hengstenberg, C, Havulinna, AS, Hastie, ND, Harris, TB, Haritunians, T, Hall, AS, Groop, LC, Gonzalez, E, Freimer, NB, Erdmann, J, Ejebe, KG, Döring, A, Dominiczak, AF, Demissie, S, Deloukas, P, de Faire, U, Crawford, G, Chen, Y-derI, Caulfield, MJ, S Boekholdt, M, Assimes, TL, Quertermous, T, Seielstad, M, Wong, TY, Tai, E-S, Feranil, AB, Kuzawa, CW, Taylor, HA, Gabriel, SB, Holm, H, Gudnason, V, Krauss, RM, Ordovas, JM, Munroe, PB, Kooner, JS, Tall, AR, Hegele, RA, Kastelein, JJP, Schadt, EE, Strachan, DP, Reilly, MP, Samani, NJ, Schunkert, H, Cupples, AL, Sandhu, MS, Ridker, PM, Rader, DJ, Kathiresan, S
Corporate/Institutional AuthorsDIAGRAM+ Consortium,, MAGIC Consortium,, GLGC Investigators,, MuTHER Consortium,, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium,, Procardis Consortium,, MAGIC investigators, GLGC Consortium,
JournalPLoS Genet
Volume8
Issue3
Paginatione1002607
Date Published2012
ISSN1553-7404
KeywordsAdiponectin, African Americans, Asian Continental Ancestry Group, Cholesterol, HDL, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Metabolic Networks and Pathways, Polymorphism, Single Nucleotide, Waist-Hip Ratio
Abstract<p>Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.</p>
DOI10.1371/journal.pgen.1002607
Alternate JournalPLoS Genet.
PubMed ID22479202
PubMed Central IDPMC3315470
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
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G0600705 / / Medical Research Council / United Kingdom
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G19/35 / / Medical Research Council / United Kingdom
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/ / Medical Research Council / United Kingdom
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