A genome-wide association search for type 2 diabetes genes in African Americans.


Palmer, ND; McDonough, CW; Hicks, PJ; Roh, BH; Wing, MR; An, SS; Hester, JM; Cooke, JN; Bostrom, MA; Rudock, ME; Talbert, ME; Lewis, JP; DIAGRAM Consortium, ; MAGIC Investigators, ; Ferrara, A; Lu, L; Ziegler, JT; Sale, MM; Divers, J; Shriner, D; Adeyemo, A; Rotimi, CN; Ng, MC; Langefeld, CD; Freedman, BI; Bowden, DW; Voight, BF; Scott, LJ; Steinthorsdottir, V; Morris, AP; 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; Langenberg, C; Hofmann, OM; Dupuis, J; Qi, L; Segrè, AV; van Hoek, M; Navarro, P; Ardlie, K; Balkau, B; Benediktsson, R; Bennett, AJ; Blagieva, R; Boerwinkle, E; Bonnycastle, LL; Boström, KB; Bravenboer, B; Bumpstead, S; Burtt, NP; Charpentier, G; Chines, PS; Cornelis, M; Couper, DJ; Crawford, G; Doney, AS; 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, PR; Jørgensen, T; Kao, WH; Klopp, N; 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; Perry, JR; Petersen, AK; Platou, C; Proença, C; Prokopenko, I; Rathmann, W; Rayner, NW; 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, GB; 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; Mohlke, KL; Morris, AD; Palmer, CN; Pramstaller, PP; Rudan, I; Sijbrands, E; Stein, LD; Tuomilehto, J; Uitterlinden, A; Walker, M; Wareham, NJ; Watanabe, RM; Abecasis, GR; Boehm, BO; Campbell, H; Daly, MJ; Hattersley, AT; Hu, FB; Meigs, JB; Pankow, JS; Pedersen, O; Wichmann, HE; Barroso, I; Florez, JC; Frayling, TM; 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; Johnson, T; Elliott, P; Rybin, D; Henneman, P; Dehghan, A; Hottenga, JJ; Song, K; Goel, A; Egan, JM; Lajunen, T; Doney, A; Kanoni, S; Cavalcanti-Proença, C; Kumari, M; Timpson, NJ; Zabena, C; Ingelsson, E; An, P; O'Connell, J; Luan, J; 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, YD; Chines, P; Clarke, R; Coin, LJ; Cooper, MN; Crisponi, L; Day, IN; de Geus, EJ; Delplanque, J; Fedson, AC; Fischer-Rosinsky, A; Forouhi, NG; Frants, R; Franzosi, MG; Galan, P; Goodarzi, MO; Graessler, J; Grundy, S; Gwilliam, R; Hallmans, G; Hammond, N; Han, X; Hartikainen, AL; Hayward, C; Heath, SC; Hercberg, S; Hicks, AA; Hillman, DR; Hingorani, AD; Hui, J; Hung, J; Jula, A; Kaakinen, M; Kaprio, J; Kesaniemi, YA; Kivimaki, M; Knight, B; Koskinen, S; Kovacs, P; Kyvik, KO; Lathrop, GM; Lawlor, DA; Le Bacquer, O; Lecoeur, C; Li, Y; Mahley, R; Mangino, M; Manning, AK; Martínez-Larrad, MT; McAteer, JB; McPherson, R; Meisinger, C; Melzer, D; Meyre, D; Mitchell, BD; Mukherjee, S; Naitza, S; Neville, MJ; Oostra, BA; Orrù, M; Pakyz, R; Paolisso, G; Pattaro, C; Pearson, D; Peden, JF; Pedersen, NL; Perola, M; Pfeiffer, AF; Pichler, I; Polasek, O; Posthuma, D; Potter, SC; Pouta, A; Province, MA; Psaty, BM; 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; Sijbrands, EJ; Silveira, A; Simpson, L; Singleton, A; Smith, NL; Sovio, U; Swift, A; Syddall, H; Syvänen, AC; Tanaka, T; 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, JC; Yarnell, JW; Zelenika, D; Zethelius, B; Zhai, G; Zhao, JH; Zillikens, MC; Borecki, IB; Loos, RJ; Meneton, P; Magnusson, PK; Nathan, DM; Williams, GH; Silander, K; Salomaa, V; Smith, GD; Bornstein, SR; Schwarz, P; Spranger, J; Karpe, F; Shuldiner, AR; Cooper, C; Dedoussis, GV; Serrano-Ríos, M; Lind, L; Palmer, LJ; Franks, PW; Ebrahim, S; Marmot, M; Kao, WH; Pramstaller, PP; Wright, AF; Stumvoll, M; Hamsten, A; Buchanan, TA; Valle, TT; Rotter, JI; Siscovick, DS; Penninx, BW; Boomsma, DI; Deloukas, P; Spector, TD; Ferrucci, L; Cao, A; Scuteri, A; Schlessinger, D; Uda, M; Ruokonen, A; Jarvelin, MR; Waterworth, DM; Vollenweider, P; Peltonen, L; Mooser, V; Sladek, R; (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PLoS One, 7 (1). e29202. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0029202

[img]
Preview
Text - Published Version
License:

Download (313kB) | Preview

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.

Item Type: Article
Faculty and Department: Faculty of Public Health and Policy > Dept of Global Health and Development
Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 22238593
Web of Science ID: 301070200019
URI: http://researchonline.lshtm.ac.uk/id/eprint/55982

Statistics


Download activity - last 12 months
Downloads since deposit
254Downloads
363Hits
Accesses by country - last 12 months
Accesses by referrer - last 12 months
Impact and interest
Additional statistics for this record are available via IRStats2

Actions (login required)

Edit Item Edit Item