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

Nicholette DPalmer; Caitrin WMcDonough; Pamela JHicks; Bong HRoh; Maria RWing; S SandyAn; Jessica MHester; Jessica NCooke; Meredith ABostrom; Megan ERudock; +380 more... Matthew ETalbert; Joshua PLewis; AssiamiraFerrara; LingyiLu; Julie TZiegler; Michele MSale; JasminDivers; DanielShriner; AdebowaleAdeyemo; Charles NRotimi; Maggie C YNg; Carl DLangefeld; Barry IFreedman; Donald WBowden; Benjamin FVoight; Laura JScott; ValgerdurSteinthorsdottir; Andrew PMorris; ChristianDina; Ryan PWelch; EleftheriaZeggini; CorneliaHuth; Yurii SAulchenko; GudmarThorleifsson; Laura JMcCulloch; TeresaFerreira; HaraldGrallert; NajafAmin; GuanmingWu; Cristen JWiller; SoumyaRaychaudhuri; Steve AMcCarroll; ClaudiaLangenberg; Oliver MHofmann; JoséeDupuis; LuQi; Ayellet VSegrè; Mandyvan Hoek; PauNavarro; KristinArdlie; BeverleyBalkau; RafnBenediktsson; Amanda JBennett; RozaBlagieva; EricBoerwinkle; Lori LBonnycastle; Kristina BengtssonBoström; BertBravenboer; SuzannahBumpstead; Noël PBurtt; GuillaumeCharpentier; Peter SChines; MarilynCornelis; David JCouper; GabeCrawford; Alex S FDoney; Katherine SElliott; Amanda LElliott; Michael RErdos; Caroline SFox; Christopher SFranklin; MarthaGanser; ChristianGieger; NielsGrarup; ToddGreen; SimonGriffin; Christopher JGroves; CandaceGuiducci; SamyHadjadj; NeelamHassanali; ChristianHerder; BoIsomaa; Anne UJackson; Paul R VJohnson; TorbenJørgensen; Wen H LKao; NormanKlopp; AugustineKong; PeterKraft; JohannaKuusisto; TorstenLauritzen; ManLi; AloysiusLieverse; Cecilia MLindgren; ValeriyaLyssenko; MichelMarre; ThomasMeitinger; KristianMidthjell; Mario AMorken; NarisuNarisu; PeterNilsson; Katharine ROwen; FelicityPayne; John R BPerry; Ann-KristinPetersen; CarlPlatou; ChristineProença; IngaProkopenko; WolfgangRathmann; N WilliamRayner; Neil RRobertson; GhislainRocheleau; MichaelRoden; Michael JSampson; RichaSaxena; Beverley MShields; PeterShrader; GunnarSigurdsson; ThomasSparsø; KlausStrassburger; Heather MStringham; QiSun; Amy JSwift; BarbaraThorand; JeanTichet; TiinamaijaTuomi; Rob Mvan Dam; Timon Wvan Haeften; Thijsvan Herpt; Jana Vvan Vliet-Ostaptchouk; G BragiWalters; Michael NWeedon; CiscaWijmenga; JacquelineWitteman; Richard NBergman; StephaneCauchi; Francis SCollins; Anna LGloyn; UlfGyllensten; TorbenHansen; Winston AHide; Graham AHitman; AlbertHofman; David JHunter; KristianHveem; MarkkuLaakso; Karen LMohlke; Andrew DMorris; Colin N APalmer; Peter PPramstaller; IgorRudan; EricSijbrands; Lincoln DStein; JaakkoTuomilehto; AndreUitterlinden; MarkWalker; Nicholas JWareham; Richard MWatanabe; Goncalo RAbecasis; Bernhard OBoehm; HarryCampbell; Mark JDaly; Andrew THattersley; Frank BHu; James BMeigs; James SPankow; OlufPedersen; H-ErichWichmann; InêsBarroso; Jose CFlorez; Timothy MFrayling; LeifGroop; RobSladek; UnnurThorsteinsdottir; James FWilson; ThomasIllig; PhilippeFroguel; Cornelia Mvan Duijn; KariStefansson; DavidAltshuler; MichaelBoehnke; Mark IMcCarthy; NicoleSoranzo; EleanorWheeler; Nicole LGlazer; NabilaBouatia-Naji; ReedikMägi; JoshuaRandall; TobyJohnson; PaulElliott; DenisRybin; PeterHenneman; AbbasDehghan; Jouke JanHottenga; KijoungSong; AnujGoel; Josephine MEgan; TainaLajunen; AlexDoney; StavroulaKanoni; ChristineCavalcanti-Proença; MeenaKumari; Nicholas JTimpson; CarinaZabena; ErikIngelsson; PingAn; JeffreyO'Connell; Jian'anLuan; AmandaElliott; Steven AMcCarroll; Rosa MariaRoccasecca; FrançoisPattou; PraveenSethupathy; YavuzAriyurek; PhilipBarter; John PBeilby; YoavBen-Shlomo; SvenBergmann; MurielleBochud; AmélieBonnefond; KnutBorch-Johnsen; YvonneBöttcher; EricBrunner; Suzannah JBumpstead; Yii-Der IdaChen; PeterChines; RobertClarke; Lachlan J MCoin; Matthew NCooper; LauraCrisponi; Ian N MDay; Eco J Cde Geus; JeromeDelplanque; Annette CFedson; AntjeFischer-Rosinsky; Nita GForouhi; RuneFrants; Maria GraziaFranzosi; PilarGalan; Mark OGoodarzi; JürgenGraessler; ScottGrundy; RhianGwilliam; GöranHallmans; NaomiHammond; XijingHan; Anna-LiisaHartikainen; CarolineHayward; Simon CHeath; SergeHercberg; Andrew AHicks; David RHillman; Aroon DHingorani; JennieHui; JoeHung; AnttiJula; MarikaKaakinen; JaakkoKaprio; Y AnteroKesaniemi; MikaKivimaki; BeatriceKnight; SeppoKoskinen; PeterKovacs; Kirsten OhmKyvik; G MarkLathrop; Debbie ALawlor; OlivierLe Bacquer; CécileLecoeur; YunLi; RobertMahley; MassimoMangino; Alisa KManning; María TeresaMartínez-Larrad; Jarred BMcAteer; RuthMcPherson; ChristaMeisinger; DavidMelzer; DavidMeyre; Braxton DMitchell; SutapaMukherjee; SilviaNaitza; Matthew JNeville; Ben AOostra; MarcoOrrù; RuthPakyz; GiuseppePaolisso; CristianPattaro; DanielPearson; John FPeden; Nancy LPedersen; MarkusPerola; Andreas F HPfeiffer; IrenePichler; OzrenPolasek; DaniellePosthuma; Simon CPotter; AnneliPouta; Michael AProvince; Bruce MPsaty; Nigel WRayner; KennethRice; SamuliRipatti; FernandoRivadeneira; OlovRolandsson; AnnelliSandbaek; ManjinderSandhu; SerenaSanna; Avan AihieSayer; PaulScheet; UdoSeedorf; Stephen JSharp; BeverleyShields; Eric J GSijbrands; AngelaSilveira; LailaSimpson; AndrewSingleton; Nicholas LSmith; UllaSovio; AmySwift; HollySyddall; Ann-ChristineSyvänen; ToshikoTanaka; AnkeTönjes; André GUitterlinden; Ko Willemsvan Dijk; DhirajVarma; SophieVisvikis-Siest; VeroniqueVitart; NicoleVogelzangs; GérardWaeber; Peter JWagner; AndrewWalley; Kim LWard; HughWatkins; Sarah HWild; GonnekeWillemsen; Jaqueline C MWitteman; John W GYarnell; DianaZelenika; BjörnZethelius; GuangjuZhai; Jing HuaZhao; M CarolaZillikens; Ingrid BBorecki; Ruth J FLoos; PierreMeneton; Patrik K EMagnusson; David MNathan; Gordon HWilliams; KaisaSilander; VeikkoSalomaa; George DaveySmith; Stefan RBornstein; PeterSchwarz; JoachimSpranger; FredrikKarpe; Alan RShuldiner; CyrusCooper; George VDedoussis; ManuelSerrano-Ríos; LarsLind; Lyle JPalmer; Paul WFranks; ShahEbrahim; MichaelMarmot; W H LindaKao; Peter PaulPramstaller; Alan FWright; MichaelStumvoll; AndersHamsten; Thomas ABuchanan; Timo TValle; Jerome IRotter; David SSiscovick; Brenda W J HPenninx; Dorret IBoomsma; PanosDeloukas; Timothy DSpector; LuigiFerrucci; AntonioCao; AngeloScuteri; DavidSchlessinger; ManuelaUda; AimoRuokonen; Marjo-RiittaJarvelin; Dawn MWaterworth; PeterVollenweider; LeenaPeltonen; VincentMooser; RobertSladek; (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PloS one, 7 (1). e29202. ISSN 1932-6203 https://material-uat.leaf.cosector.com/id/eprint/20693
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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.


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