Identification of type 2 diabetes loci in 433,540 East Asian individuals.
Cassandra N SpracklenMomoko HorikoshiYoung Jin KimKuang LinFiona BraggSanghoon MoonKen SuzukiClaudia Ha-Ting TamYasuharu TabaraSoo-Heon KwakFumihiko TakeuchiJirong LongVictor J Y LimJin Fang ChaiChien-Hsiun ChenMasahiro NakatochiJie YaoHyeok Sun ChoiApoorva K IyengarHannah J PerrinSarah M BrotmanMartijn van de BuntAnna L GloynJennifer E BelowMichael BoehnkeDonald W BowdenJohn C ChambersAnubha MahajanMark I McCarthyMaggie C Y NgLauren E PettyWeihua ZhangAndrew P MorrisLinda S AdairMasato AkiyamaZheng BianJuliana C N ChanLi-Ching ChangMiao-Li CheeYii-Der Ida ChenYuan-Tsong ChenZhengming ChenLee-Ming ChuangShufa DuPenny Gordon-LarsenMyron GrossXiuqing GuoYu GuoSohee HanAnnie-Green HowardWei HuangYi-Jen HungMi Yeong HwangChii-Min HwuSahoko IchiharaMasato IsonoHye-Mi JangGuozhi JiangJost Bruno JonasYoichiro KamataniTomohiro KatsuyaTakahisa KawaguchiChiea Chuen KhorKatsuhiko KoharaMyung-Shik LeeNanette R LeeLiming LiJian-Jun LiuAndrea O LukJun LvYukinori OkadaMark A PereiraSabanayagam CharumathiJinxiu ShiDong Mun ShinWing Yee SoAtsushi TakahashiChristopher Wai Kei LamFuu-Jen TsaiRob M van DamYong-Bing XiangKen YamamotoToshimasa YamauchiKyungheon YoonCanqing YuWoon-Puay KohLiang ZhangQuan LongMichiya IgaseYoon Shin ChoJerome I RotterYa-Xing WangWayne H H SheuMitsuhiro YokotaJer-Yuarn WuChing-Yu ChengTien-Yin WongXiao-Ou ShuNorihiro KatoKyong-Soo ParkE-Shyong TaiFumihiko MatsudaWoon-Puay KohRonald Ching-Wan MaShiro MaedaIona Y MillwoodJuyoung LeeTakashi KadowakiRobin G WaltersBong-Jo KimKaren L MohlkeXueling S SimPublished in: Nature (2020)
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.
Keyphrases
- genome wide
- genome wide association
- genome wide association study
- type diabetes
- dna methylation
- copy number
- cardiovascular disease
- systematic review
- bioinformatics analysis
- skeletal muscle
- gene expression
- adipose tissue
- oxidative stress
- glycemic control
- big data
- deep learning
- cell death
- cell proliferation
- meta analyses
- endoplasmic reticulum stress
- genome wide identification
- transcription factor
- metabolic syndrome
- artificial intelligence
- genome wide analysis