Identification of type 2 diabetes loci in 433,540 East Asian individuals
Journal
Nature
Date Issued
2020
Author(s)
Spracklen C.N.
Horikoshi M.
Kim Y.J.
Lin K.
Bragg F.
Moon S.
Suzuki K.
Tam C.H.T.
Tabara Y.
Kwak S.-H.
Takeuchi F.
Long J.
Lim V.J.Y.
Chai J.-F.
Chen C.-H.
Nakatochi M.
Yao J.
Choi H.S.
Iyengar A.K.
Perrin H.J.
Brotman S.M.
van de Bunt M.
Gloyn A.L.
Below J.E.
Boehnke M.
Bowden D.W.
Chambers J.C.
Mahajan A.
McCarthy M.I.
Ng M.C.Y.
Petty L.E.
Zhang W.
Morris A.P.
Adair L.S.
Akiyama M.
Bian Z.
Chan J.C.N.
Chang L.-C.
Chee M.-L.
Chen Y.-D.I.
Chen Y.-T.
Chen Z.
Du S.
Gordon-Larsen P.
Gross M.
Guo X.
Guo Y.
Han S.
Howard A.-G.
Huang W.
Hung Y.-J.
Hwang M.Y.
Hwu C.-M.
Ichihara S.
Isono M.
Jang H.-M.
Jiang G.
Jonas J.B.
Kamatani Y.
Katsuya T.
Kawaguchi T.
Khor C.-C.
Kohara K.
Lee M.-S.
Lee N.R.
Li L.
Liu J.
Luk A.O.
Lv J.
Okada Y.
Pereira M.A.
Sabanayagam C.
Shi J.
Shin D.M.
So W.Y.
Takahashi A.
Tomlinson B.
Tsai F.-J.
van Dam R.M.
Xiang Y.-B.
Yamamoto K.
Yamauchi T.
Yoon K.
Yu C.
Yuan J.-M.
Zhang L.
Zheng W.
Igase M.
Cho Y.S.
Rotter J.I.
Wang Y.-X.
Sheu W.H.H.
Yokota M.
Wu J.-Y.
Cheng C.-Y.
Wong T.-Y.
Shu X.-O.
Kato N.
Park K.-S.
Tai E.-S.
Matsuda F.
Koh W.-P.
Ma R.C.W.
Maeda S.
Millwood I.Y.
Lee J.
Kadowaki T.
Walters R.G.
Kim B.-J.
Mohlke K.L.
Sim X.
Abstract
Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes—NKX6-3 and ANK1—in different tissues4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways. ? 2020, The Author(s), under exclusive licence to Springer Nature Limited.
SDGs
Other Subjects
microRNA; aldehyde dehydrogenase isoenzyme 2; ALDH2 protein, human; ANK1 protein, human; ankyrin; eye protein; GDAP protein; homeodomain protein; messenger RNA; nerve protein; Nkx6-3 protein, human; Sine oculis homeobox homolog 3 protein; transcription factor; transcription factor PTF1; ancestry; body mass; diabetes; gene expression; genome; identification method; index method; adipose tissue cell; ALDH2 gene; ANK1 gene; Article; body mass; cell differentiation; controlled study; East Asian; European; female; GDAP1 gene; gender; gene; gene cluster; gene expression; gene identification; gene locus; genetic association; genetic predisposition; genetic variability; genome-wide association study; human; major clinical study; male; muscle cell; NKX6 3 gene; non insulin dependent diabetes mellitus; priority journal; PTF1A gene; risk factor; SIX3 gene; allele; Asian continental ancestry group; case control study; ethnology; Europe; Far East; genetic predisposition; genetic transcription; genetics; meta analysis; non insulin dependent diabetes mellitus; Far East; Aldehyde Dehydrogenase, Mitochondrial; Alleles; Ankyrins; Asian Continental Ancestry Group; Body Mass Index; Case-Control Studies; Diabetes Mellitus, Type 2; Europe; Eye Proteins; Far East; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; Homeodomain Proteins; Humans; Male; Nerve Tissue Proteins; RNA, Messenger; Transcription Factors; Transcription, Genetic
Publisher
Nature Research
Type
journal article