RT Journal Article
SR Electronic
T1 Identification of type 2 diabetes loci in 433,540 East Asian individuals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 685172
DO 10.1101/685172
A1 Cassandra N Spracklen
A1 Momoko Horikoshi
A1 Young Jin Kim
A1 Kuang Lin
A1 Fiona Bragg
A1 Sanghoon Moon
A1 Ken Suzuki
A1 Claudia HT Tam
A1 Yasuharu Tabara
A1 Soo-Heon Kwak
A1 Fumihiko Takeuchi
A1 Jirong Long
A1 Victor JY Lim
A1 Jin-Fang Chai
A1 Chien-Hsiun Chen
A1 Masahiro Nakatochi
A1 Jie Yao
A1 Hyeok Sun Choi
A1 Apoorva K Iyengar
A1 Hannah J Perrin
A1 Sarah M Brotman
A1 Martijn van de Bunt
A1 Anna L Gloyn
A1 Jennifer E Below
A1 Michael Boehnke
A1 Donald W Bowden
A1 John C Chambers
A1 Anubha Mahajan
A1 Mark I McCarthy
A1 Maggie CY Ng
A1 Lauren E Petty
A1 Weihua Zhang
A1 Andrew P Morris
A1 Linda S Adair
A1 Zheng Bian
A1 Juliana CN Chan
A1 Li-Ching Chang
A1 Miao-Li Chee
A1 Yii-Der Ida Chen
A1 Yuan-Tsong Chen
A1 Zhengming Chen
A1 Lee-Ming Chuang
A1 Shufa Du
A1 Penny Gordon-Larsen
A1 Myron Gross
A1 Xiuqing Guo
A1 Yu Guo
A1 Sohee Han
A1 Annie-Green Howard
A1 Wei Huang
A1 Yi-Jen Hung
A1 Mi Yeong Hwang
A1 Chii-Min Hwu
A1 Sahoko Ichihara
A1 Masato Isono
A1 Hye-Mi Jang
A1 Guozhi Jiang
A1 Jost B Jonas
A1 Yoichiro Kamatani
A1 Tomohiro Katsuya
A1 Takahisa Kawaguchi
A1 Chiea-Chuen Khor
A1 Katsuhiko Kohara
A1 Myung-Shik Lee
A1 Nannette R Lee
A1 Liming Li
A1 Jianjun Liu
A1 Andrea O Luk
A1 Jun Lv
A1 Yukinori Okada
A1 Mark A Pereira
A1 Charumathi Sabanayagam
A1 Jinxiu Shi
A1 Dong Mun Shin
A1 Wing Yee So
A1 Atsushi Takahashi
A1 Brian Tomlinson
A1 Fuu-Jen Tsai
A1 Rob M van Dam
A1 Yong-Bing Xiang
A1 Ken Yamamoto
A1 Toshimasa Yamauchi
A1 Kyungheon Yoon
A1 Canqing Yu
A1 Jian-Min Yuan
A1 Liang Zhang
A1 Wei Zheng
A1 Michiya Igase
A1 Yoon Shin Cho
A1 Jerome I Rotter
A1 Ya-Xing Wang
A1 Wayne HH Sheu
A1 Mitsuhiro Yokota
A1 Jer-Yuarn Wu
A1 Ching-Yu Cheng
A1 Tien-Yin Wong
A1 Xiao-Ou Shu
A1 Norihiro Kato
A1 Kyong-Soo Park
A1 E-Shyong Tai
A1 Fumihiko Matsuda
A1 Woon-Puay Koh
A1 Ronald CW Ma
A1 Shiro Maeda
A1 Iona Y Millwood
A1 Juyoung Lee
A1 Takashi Kadowaki
A1 Robin G Walters
A1 Bong-Jo Kim
A1 Karen L Mohlke
A1 Xueling Sim
YR 2019
UL http://biorxiv.org/content/early/2019/06/28/685172.abstract
AB Meta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.Type 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic β cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.