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Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

Tuesday,2013-10-01 10:31 America/Los_Angeles — poolea2
TitleLarge-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.
Publication TypeJournal Article
Year of Publication2012
AuthorsScott, RA, Lagou, V, Welch, RP, Wheeler, E, Montasser, ME, Luan, J'an, Mägi, R, Strawbridge, RJ, Rehnberg, E, Gustafsson, S, Kanoni, S, Rasmussen-Torvik, LJ, Yengo, L, Lecoeur, C, Shungin, D, Sanna, S, Sidore, C, Johnson, PCD, J Jukema, W, Johnson, T, Mahajan, A, Verweij, N, Thorleifsson, G, Hottenga, J-J, Shah, S, Smith, AV, Sennblad, B, Gieger, C, Salo, P, Perola, M, Timpson, NJ, Evans, DM, St Pourcain, B, Wu, Y, Andrews, JS, Hui, J, Bielak, LF, Zhao, W, Horikoshi, M, Navarro, P, Isaacs, A, O'Connell, JR, Stirrups, K, Vitart, V, Hayward, C, Esko, T, Mihailov, E, Fraser, RM, Fall, T, Voight, BF, Raychaudhuri, S, Chen, H, Lindgren, CM, Morris, AP, Rayner, NW, Robertson, N, Rybin, D, Liu, C-T, Beckmann, JS, Willems, SM, Chines, PS, Jackson, AU, Kang, HMin, Stringham, HM, Song, K, Tanaka, T, Peden, JF, Goel, A, Hicks, AA, An, P, Müller-Nurasyid, M, Franco-Cereceda, A, Folkersen, L, Marullo, L, Jansen, H, Oldehinkel, AJ, Bruinenberg, M, Pankow, JS, North, KE, Forouhi, NG, Loos, RJF, Edkins, S, Varga, TV, Hallmans, G, Oksa, H, Antonella, M, Nagaraja, R, Trompet, S, Ford, I, Bakker, SJL, Kong, A, Kumari, M, Gigante, B, Herder, C, Munroe, PB, Caulfield, M, Antti, J, Mangino, M, Small, K, Miljkovic, I, Liu, Y, Atalay, M, Kiess, W, James, AL, Rivadeneira, F, Uitterlinden, AG, Palmer, CNA, Doney, ASF, Willemsen, G, Smit, JH, Campbell, S, Polasek, O, Bonnycastle, LL, Hercberg, S, Dimitriou, M, Bolton, JL, Fowkes, GR, Kovacs, P, Lindström, J, Zemunik, T, Bandinelli, S, Wild, SH, Basart, HV, Rathmann, W, Grallert, H, Maerz, W, Kleber, ME, Boehm, BO, Peters, A, Pramstaller, PP, Province, MA, Borecki, IB, Hastie, ND, Rudan, I, Campbell, H, Watkins, H, Farrall, M, Stumvoll, M, Ferrucci, L, Waterworth, DM, Bergman, RN, Collins, FS, Tuomilehto, J, Watanabe, RM, de Geus, EJC, Penninx, BW, Hofman, A, Oostra, BA, Psaty, BM, Vollenweider, P, Wilson, JF, Wright, AF, G Hovingh, K, Metspalu, A, Uusitupa, M, Magnusson, PKE, Kyvik, KO, Kaprio, J, Price, JF, Dedoussis, GV, Deloukas, P, Meneton, P, Lind, L, Boehnke, M, Shuldiner, AR, van Duijn, CM, Morris, AD, Toenjes, A, Peyser, PA, Beilby, JP, Körner, A, Kuusisto, J, Laakso, M, Bornstein, SR, Schwarz, PEH, Lakka, TA, Rauramaa, R, Adair, LS, Smith, GD, Spector, TD, Illig, T, de Faire, U, Hamsten, A, Gudnason, V, Kivimaki, M, Hingorani, A, Keinanen-Kiukaanniemi, SM, Saaristo, TE, Boomsma, DI, Stefansson, K, van der Harst, P, Dupuis, J, Pedersen, NL, Sattar, N, Harris, TB, Cucca, F, Ripatti, S, Salomaa, V, Mohlke, KL, Balkau, B, Froguel, P, Pouta, A, Jarvelin, M-R, Wareham, NJ, Bouatia-Naji, N, McCarthy, MI, Franks, PW, Meigs, JB, Teslovich, TM, Florez, JC, Langenberg, C, Ingelsson, E, Prokopenko, I, Barroso, I
Corporate/Institutional AuthorsDIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium
JournalNat Genet
Volume44
Issue9
Pagination991-1005
Date Published2012 Sep
ISSN1546-1718
KeywordsAdult, Animals, Blood Glucose, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Male, Metabolic Networks and Pathways, Mice, Osmolar Concentration, Quantitative Trait Loci
Abstract<p>Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.</p>
DOI10.1038/ng.2385
Alternate JournalNat. Genet.
PubMed ID22885924
PubMed Central IDPMC3433394
Grant ListN01HC55020 / HL / NHLBI NIH HHS / United States
M01-RR00425 / RR / NCRR NIH HHS / United States
R01 DK078616 / DK / NIDDK NIH HHS / United States
AG04563 / AG / NIA NIH HHS / United States
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DK078150 / DK / NIDDK NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01-HL-088215 / HL / NHLBI NIH HHS / United States
CZB/4/710 / / Chief Scientist Office / United Kingdom
G9521010 / / Medical Research Council / United Kingdom
CZB/4/672 / / Chief Scientist Office / United Kingdom
098017 / / Wellcome Trust / United Kingdom
R01 MH063706 / MH / NIMH NIH HHS / United States
R01 HL075366 / HL / NHLBI NIH HHS / United States
P30 ES010126 / ES / NIEHS NIH HHS / United States
092731 / / Wellcome Trust / United Kingdom
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N01HC55018 / HL / NHLBI NIH HHS / United States
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MC_UP_A100_1003 / / Medical Research Council / United Kingdom
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G19/35 / / Medical Research Council / United Kingdom
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N01 AG062101 / AG / NIA NIH HHS / United States
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G20234 / / Biotechnology and Biological Sciences Research Council / United Kingdom
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GR069224 / / Wellcome Trust / United Kingdom
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