Palmer, ND and McDonough, CW and Hicks, PJ and Roh, BH and Wing, MR and An, SS and Hester, JM and Cooke, JN and Bostrom, MA and Rudock, ME and Talbert, ME and Lewis, JP and DIAGRAM Consortium, and MAGIC Investigators, and Ferrara, A and Lu, L and Ziegler, JT and Sale, MM and Divers, J and Shriner, D and Adeyemo, A and Rotimi, CN and Ng, MC and Langefeld, CD and Freedman, BI and Bowden, DW and Voight, BF and Scott, LJ and Steinthorsdottir, V and Morris, AP and Dina, C and Welch, RP and Zeggini, E and Huth, C and Aulchenko, YS and Thorleifsson, G and McCulloch, LJ and Ferreira, T and Grallert, H and Amin, N and Wu, G and Willer, CJ and Raychaudhuri, S and McCarroll, SA and Langenberg, C and Hofmann, OM and Dupuis, J and Qi, L and Segrè, AV and van Hoek, M and Navarro, P and Ardlie, K and Balkau, B and Benediktsson, R and Bennett, AJ and Blagieva, R and Boerwinkle, E and Bonnycastle, LL and Boström, KB and Bravenboer, B and Bumpstead, S and Burtt, NP and Charpentier, G and Chines, PS and Cornelis, M and Couper, DJ and Crawford, G and Doney, AS and Elliott, KS and Elliott, AL and Erdos, MR and Fox, CS and Franklin, CS and Ganser, M and Gieger, C and Grarup, N and Green, T and Griffin, S and Groves, CJ and Guiducci, C and Hadjadj, S and Hassanali, N and Herder, C and Isomaa, B and Jackson, AU and Johnson, PR and Jørgensen, T and Kao, WH and Klopp, N and Kong, A and Kraft, P and Kuusisto, J and Lauritzen, T and Li, M and Lieverse, A and Lindgren, CM and Lyssenko, V and Marre, M and Meitinger, T and Midthjell, K and Morken, MA and Narisu, N and Nilsson, P and Owen, KR and Payne, F and Perry, JR and Petersen, AK and Platou, C and Proença, C and Prokopenko, I and Rathmann, W and Rayner, NW and Robertson, NR and Rocheleau, G and Roden, M and Sampson, MJ and Saxena, R and Shields, BM and Shrader, P and Sigurdsson, G and Sparsø, T and Strassburger, K and Stringham, HM and Sun, Q and Swift, AJ and Thorand, B and Tichet, J and Tuomi, T and van Dam, RM and van Haeften, TW and van Herpt, T and van Vliet-Ostaptchouk, JV and Walters, GB and Weedon, MN and Wijmenga, C and Witteman, J and Bergman, RN and Cauchi, S and Collins, FS and Gloyn, AL and Gyllensten, U and Hansen, T and Hide, WA and Hitman, GA and Hofman, A and Hunter, DJ and Hveem, K and Laakso, M and Mohlke, KL and Morris, AD and Palmer, CN and Pramstaller, PP and Rudan, I and Sijbrands, E and Stein, LD and Tuomilehto, J and Uitterlinden, A and Walker, M and Wareham, NJ and Watanabe, RM and Abecasis, GR and Boehm, BO and Campbell, H and Daly, MJ and Hattersley, AT and Hu, FB and Meigs, JB and Pankow, JS and Pedersen, O and Wichmann, HE and Barroso, I and Florez, JC and Frayling, TM and Groop, L and Sladek, R and Thorsteinsdottir, U and Wilson, JF and Illig, T and Froguel, P and van Duijn, CM and Stefansson, K and Altshuler, D and Boehnke, M and McCarthy, MI and Soranzo, N and Wheeler, E and Glazer, NL and Bouatia-Naji, N and Mägi, R and Randall, J and Johnson, T and Elliott, P and Rybin, D and Henneman, P and Dehghan, A and Hottenga, JJ and Song, K and Goel, A and Egan, JM and Lajunen, T and Doney, A and Kanoni, S and Cavalcanti-Proença, C and Kumari, M and Timpson, NJ and Zabena, C and Ingelsson, E and An, P and O'Connell, J and Luan, J and Elliott, A and McCarroll, SA and Roccasecca, RM and Pattou, F and Sethupathy, P and Ariyurek, Y and Barter, P and Beilby, JP and Ben-Shlomo, Y and Bergmann, S and Bochud, M and Bonnefond, A and Borch-Johnsen, K and Böttcher, Y and Brunner, E and Bumpstead, SJ and Chen, YD and Chines, P and Clarke, R and Coin, LJ and Cooper, MN and Crisponi, L and Day, IN and de Geus, EJ and Delplanque, J and Fedson, AC and Fischer-Rosinsky, A and Forouhi, NG and Frants, R and Franzosi, MG and Galan, P and Goodarzi, MO and Graessler, J and Grundy, S and Gwilliam, R and Hallmans, G and Hammond, N and Han, X and Hartikainen, AL and Hayward, C and Heath, SC and Hercberg, S and Hicks, AA and Hillman, DR and Hingorani, AD and Hui, J and Hung, J and Jula, A and Kaakinen, M and Kaprio, J and Kesaniemi, YA and Kivimaki, M and Knight, B and Koskinen, S and Kovacs, P and Kyvik, KO and Lathrop, GM and Lawlor, DA and Le Bacquer, O and Lecoeur, C and Li, Y and Mahley, R and Mangino, M and Manning, AK and Martínez-Larrad, MT and McAteer, JB and McPherson, R and Meisinger, C and Melzer, D and Meyre, D and Mitchell, BD and Mukherjee, S and Naitza, S and Neville, MJ and Oostra, BA and Orrù, M and Pakyz, R and Paolisso, G and Pattaro, C and Pearson, D and Peden, JF and Pedersen, NL and Perola, M and Pfeiffer, AF and Pichler, I and Polasek, O and Posthuma, D and Potter, SC and Pouta, A and Province, MA and Psaty, BM and Rayner, NW and Rice, K and Ripatti, S and Rivadeneira, F and Rolandsson, O and Sandbaek, A and Sandhu, M and Sanna, S and Sayer, AA and Scheet, P and Seedorf, U and Sharp, SJ and Shields, B and Sijbrands, EJ and Silveira, A and Simpson, L and Singleton, A and Smith, NL and Sovio, U and Swift, A and Syddall, H and Syvänen, AC and Tanaka, T and Tönjes, A and Uitterlinden, AG and van Dijk, KW and Varma, D and Visvikis-Siest, S and Vitart, V and Vogelzangs, N and Waeber, G and Wagner, PJ and Walley, A and Ward, KL and Watkins, H and Wild, SH and Willemsen, G and Witteman, JC and Yarnell, JW and Zelenika, D and Zethelius, B and Zhai, G and Zhao, JH and Zillikens, MC and Borecki, IB and Loos, RJ and Meneton, P and Magnusson, PK and Nathan, DM and Williams, GH and Silander, K and Salomaa, V and Smith, GD and Bornstein, SR and Schwarz, P and Spranger, J and Karpe, F and Shuldiner, AR and Cooper, C and Dedoussis, GV and Serrano-Ríos, M and Lind, L and Palmer, LJ and Franks, PW and Ebrahim, S and Marmot, M and Kao, WH and Pramstaller, PP and Wright, AF and Stumvoll, M and Hamsten, A and Buchanan, TA and Valle, TT and Rotter, JI and Siscovick, DS and Penninx, BW and Boomsma, DI and Deloukas, P and Spector, TD and Ferrucci, L and Cao, A and Scuteri, A and Schlessinger, D and Uda, M and Ruokonen, A and Jarvelin, MR and Waterworth, DM and Vollenweider, P and Peltonen, L and Mooser, V and Sladek, R (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One , 7 (1) , Article e29202 . 10.1371/journal.pone.0029202.
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Abstract
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
| Type: | Article |
|---|---|
| Title: | A genome-wide association search for type 2 diabetes genes in African Americans. |
| Location: | United States |
| Open access status: | An open access publication. A version is also available from UCL Discovery. |
| DOI: | 10.1371/journal.pone.0029202 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0029202 |
| Language: | English |
| Additional information: | PMCID: PMC3251563 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSC268200782096C. This work was supported by NIH grants K99 DK081350 (NDP), R01 DK066358 (DWB), R01 DK053591 (DWB), R01 HL56266 (BIF), R01 DK070941 (BIF) and in part by the General Clinical Research Center of the Wake Forest University School of Medicine grant M01 RR07122. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Adult, African Americans, Aged, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Validation Studies as Topic |
| UCL classification: | UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health Care > Epidemiology and Public Health |
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