Identification of type 2 diabetes loci in 433,540 East Asian individuals

Cassandra N. Spracklen; Momoko Horikoshi; Young Jin Kim; Kuang Lin; Fiona Bragg; Sanghoon Moon; Ken Suzuki; Claudia H.T. Tam; Yasuharu Tabara; Soo Heon Kwak; Fumihiko Takeuchi; Jirong Long; Victor J.Y. Lim; Jin Fang Chai; Chien Hsiun Chen; Masahiro Nakatochi; Jie Yao; Hyeok Sun Choi; Apoorva K. Iyengar; Hannah J. Perrin; Sarah M. Brotman; Martijn van de Bunt; Anna L. Gloyn; Jennifer E. Below; Michael Boehnke; Donald W. Bowden; John C. Chambers; Anubha Mahajan; Mark I. McCarthy; Maggie C.Y. Ng; Lauren E. Petty; Weihua Zhang; Andrew P. Morris; Linda S. Adair; Masato Akiyama; Zheng Bian; Juliana C.N. Chan; Li Ching Chang; Miao Li Chee; Yii Der Ida Chen; Yuan Tsong Chen; Zhengming Chen; Lee Ming Chuang; Shufa Du; Penny Gordon-Larsen; Myron Gross; Xiuqing Guo; Yu Guo; Sohee Han; Annie Green Howard; Wei Huang; Yi Jen Hung; Mi Yeong Hwang; Chii Min Hwu; Sahoko Ichihara; Masato Isono; Hye Mi Jang; Guozhi Jiang; Jost B. Jonas; Yoichiro Kamatani; Tomohiro Katsuya; Takahisa Kawaguchi; Chiea Chuen Khor; Katsuhiko Kohara; Myung Shik Lee; Nanette R. Lee; Liming Li; Jianjun Liu; Andrea O. Luk; Jun Lv; Yukinori Okada; Mark A. Pereira; Charumathi Sabanayagam; Jinxiu Shi; Dong Mun Shin; Wing Yee So; Atsushi Takahashi; Brian Tomlinson; Fuu Jen Tsai; Rob M. van Dam; Yong Bing Xiang; Ken Yamamoto; Toshimasa Yamauchi; Kyungheon Yoon; Canqing Yu; Jian Min Yuan; Liang Zhang; Wei Zheng; Michiya Igase; Yoon Shin Cho; Jerome I. Rotter; Ya Xing Wang; Wayne H.H. Sheu; Mitsuhiro Yokota; Jer Yuarn Wu; Ching Yu Cheng; Tien Yin Wong; Xiao Ou Shu; Norihiro Kato; Kyong Soo Park; E. Shyong Tai; Fumihiko Matsuda; Woon Puay Koh; Ronald C.W. Ma; Shiro Maeda; Iona Y. Millwood; Juyoung Lee; Takashi Kadowaki; Robin G. Walters; Bong Jo Kim; Karen L. Mohlke; Xueling Sim

doi:10.1038/s41586-020-2263-3

Identification of type 2 diabetes loci in 433,540 East Asian individuals

Cassandra N. Spracklen, Momoko Horikoshi, Young Jin Kim, Kuang Lin, Fiona Bragg, Sanghoon Moon, Ken Suzuki, Claudia H.T. Tam, Yasuharu Tabara, Soo Heon Kwak, Fumihiko Takeuchi, Jirong Long, Victor J.Y. Lim, Jin Fang Chai, Chien Hsiun Chen, Masahiro Nakatochi, Jie Yao, Hyeok Sun Choi, Apoorva K. Iyengar, Hannah J. PerrinSarah M. Brotman, Martijn van de Bunt, Anna L. Gloyn, Jennifer E. Below, Michael Boehnke, Donald W. Bowden, John C. Chambers, Anubha Mahajan, Mark I. McCarthy, Maggie C.Y. Ng, Lauren E. Petty, Weihua Zhang, Andrew P. Morris, Linda S. Adair, Masato Akiyama, Zheng Bian, Juliana C.N. Chan, Li Ching Chang, Miao Li Chee, Yii Der Ida Chen, Yuan Tsong Chen, Zhengming Chen, Lee Ming Chuang, Shufa Du, Penny Gordon-Larsen, Myron Gross, Xiuqing Guo, Yu Guo, Sohee Han, Annie Green Howard, Wei Huang, Yi Jen Hung, Mi Yeong Hwang, Chii Min Hwu, Sahoko Ichihara, Masato Isono, Hye Mi Jang, Guozhi Jiang, Jost B. Jonas, Yoichiro Kamatani, Tomohiro Katsuya, Takahisa Kawaguchi, Chiea Chuen Khor, Katsuhiko Kohara, Myung Shik Lee, Nanette R. Lee, Liming Li, Jianjun Liu, Andrea O. Luk, Jun Lv, Yukinori Okada, Mark A. Pereira, Charumathi Sabanayagam, Jinxiu Shi, Dong Mun Shin, Wing Yee So, Atsushi Takahashi, Brian Tomlinson, Fuu Jen Tsai, Rob M. van Dam, Yong Bing Xiang, Ken Yamamoto, Toshimasa Yamauchi, Kyungheon Yoon, Canqing Yu, Jian Min Yuan, Liang Zhang, Wei Zheng, Michiya Igase, Yoon Shin Cho, Jerome I. Rotter, Ya Xing Wang, Wayne H.H. Sheu, Mitsuhiro Yokota, Jer Yuarn Wu, Ching Yu Cheng, Tien Yin Wong, Xiao Ou Shu, Norihiro Kato, Kyong Soo Park, E. Shyong Tai, Fumihiko Matsuda, Woon Puay Koh, Ronald C.W. Ma, Shiro Maeda, Iona Y. Millwood, Juyoung Lee, Takashi Kadowaki, Robin G. Walters, Bong Jo Kim, Karen L. Mohlke, Xueling Sim

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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 tissues^4–6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Original language	English (US)
Pages (from-to)	240-245
Number of pages	6
Journal	Nature
Volume	582
Issue number	7811
DOIs	https://doi.org/10.1038/s41586-020-2263-3
State	Published - Jun 11 2020

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Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.

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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., ... Sim, X. (2020). Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature, 582(7811), 240-245. https://doi.org/10.1038/s41586-020-2263-3

Spracklen, CN, Horikoshi, M, Kim, YJ, Lin, K, Bragg, F, Moon, S, Suzuki, K, Tam, CHT, Tabara, Y, Kwak, SH, Takeuchi, F, Long, J, Lim, VJY, Chai, JF, Chen, CH, Nakatochi, M, Yao, J, Choi, HS, Iyengar, AK, Perrin, HJ, Brotman, SM, van de Bunt, M, Gloyn, AL, Below, JE, Boehnke, M, Bowden, DW, Chambers, JC, Mahajan, A, McCarthy, MI, Ng, MCY, Petty, LE, Zhang, W, Morris, AP, Adair, LS, Akiyama, M, Bian, Z, Chan, JCN, Chang, LC, Chee, ML, Chen, YDI, Chen, YT, Chen, Z, Chuang, LM, Du, S, Gordon-Larsen, P, Gross, M, Guo, X, Guo, Y, Han, S, Howard, AG, Huang, W, Hung, YJ, Hwang, MY, Hwu, CM, Ichihara, S, Isono, M, Jang, HM, Jiang, G, Jonas, JB, Kamatani, Y, Katsuya, T, Kawaguchi, T, Khor, CC, Kohara, K, Lee, MS, Lee, NR, Li, L, Liu, J, Luk, AO, Lv, J, Okada, Y, Pereira, MA, Sabanayagam, C, Shi, J, Shin, DM, So, WY, Takahashi, A, Tomlinson, B, Tsai, FJ, van Dam, RM, Xiang, YB, Yamamoto, K, Yamauchi, T, Yoon, K, Yu, C, Yuan, JM, Zhang, L, Zheng, W, Igase, M, Cho, YS, Rotter, JI, Wang, YX, Sheu, WHH, Yokota, M, Wu, JY, Cheng, CY, Wong, TY, Shu, XO, Kato, N, Park, KS, Tai, ES, Matsuda, F, Koh, WP, Ma, RCW, Maeda, S, Millwood, IY, Lee, J, Kadowaki, T, Walters, RG, Kim, BJ, Mohlke, KL & Sim, X 2020, 'Identification of type 2 diabetes loci in 433,540 East Asian individuals', Nature, vol. 582, no. 7811, pp. 240-245. https://doi.org/10.1038/s41586-020-2263-3

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title = "Identification of type 2 diabetes loci in 433,540 East Asian individuals",

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.",

author = "Spracklen, {Cassandra N.} and Momoko Horikoshi and Kim, {Young Jin} and Kuang Lin and Fiona Bragg and Sanghoon Moon and Ken Suzuki and Tam, {Claudia H.T.} and Yasuharu Tabara and Kwak, {Soo Heon} and Fumihiko Takeuchi and Jirong Long and Lim, {Victor J.Y.} and Chai, {Jin Fang} and Chen, {Chien Hsiun} and Masahiro Nakatochi and Jie Yao and Choi, {Hyeok Sun} and Iyengar, {Apoorva K.} and Perrin, {Hannah J.} and Brotman, {Sarah M.} and {van de Bunt}, Martijn and Gloyn, {Anna L.} and Below, {Jennifer E.} and Michael Boehnke and Bowden, {Donald W.} and Chambers, {John C.} and Anubha Mahajan and McCarthy, {Mark I.} and Ng, {Maggie C.Y.} and Petty, {Lauren E.} and Weihua Zhang and Morris, {Andrew P.} and Adair, {Linda S.} and Masato Akiyama and Zheng Bian and Chan, {Juliana C.N.} and Chang, {Li Ching} and Chee, {Miao Li} and Chen, {Yii Der Ida} and Chen, {Yuan Tsong} and Zhengming Chen and Chuang, {Lee Ming} and Shufa Du and Penny Gordon-Larsen and Myron Gross and Xiuqing Guo and Yu Guo and Sohee Han and Howard, {Annie Green} and Wei Huang and Hung, {Yi Jen} and Hwang, {Mi Yeong} and Hwu, {Chii Min} and Sahoko Ichihara and Masato Isono and Jang, {Hye Mi} and Guozhi Jiang and Jonas, {Jost B.} and Yoichiro Kamatani and Tomohiro Katsuya and Takahisa Kawaguchi and Khor, {Chiea Chuen} and Katsuhiko Kohara and Lee, {Myung Shik} and Lee, {Nanette R.} and Liming Li and Jianjun Liu and Luk, {Andrea O.} and Jun Lv and Yukinori Okada and Pereira, {Mark A.} and Charumathi Sabanayagam and Jinxiu Shi and Shin, {Dong Mun} and So, {Wing Yee} and Atsushi Takahashi and Brian Tomlinson and Tsai, {Fuu Jen} and {van Dam}, {Rob M.} and Xiang, {Yong Bing} and Ken Yamamoto and Toshimasa Yamauchi and Kyungheon Yoon and Canqing Yu and Yuan, {Jian Min} and Liang Zhang and Wei Zheng and Michiya Igase and Cho, {Yoon Shin} and Rotter, {Jerome I.} and Wang, {Ya Xing} and Sheu, {Wayne H.H.} and Mitsuhiro Yokota and Wu, {Jer Yuarn} and Cheng, {Ching Yu} and Wong, {Tien Yin} and Shu, {Xiao Ou} and Norihiro Kato and Park, {Kyong Soo} and Tai, {E. Shyong} and Fumihiko Matsuda and Koh, {Woon Puay} and Ma, {Ronald C.W.} and Shiro Maeda and Millwood, {Iona Y.} and Juyoung Lee and Takashi Kadowaki and Walters, {Robin G.} and Kim, {Bong Jo} and Mohlke, {Karen L.} and Xueling Sim",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = jun,

day = "11",

doi = "10.1038/s41586-020-2263-3",

language = "English (US)",

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pages = "240--245",

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T1 - Identification of type 2 diabetes loci in 433,540 East Asian individuals

AU - Spracklen, Cassandra N.

AU - Horikoshi, Momoko

AU - Kim, Young Jin

AU - Lin, Kuang

AU - Bragg, Fiona

AU - Moon, Sanghoon

AU - Suzuki, Ken

AU - Tam, Claudia H.T.

AU - Tabara, Yasuharu

AU - Kwak, Soo Heon

AU - Takeuchi, Fumihiko

AU - Long, Jirong

AU - Lim, Victor J.Y.

AU - Chai, Jin Fang

AU - Chen, Chien Hsiun

AU - Nakatochi, Masahiro

AU - Yao, Jie

AU - Choi, Hyeok Sun

AU - Iyengar, Apoorva K.

AU - Perrin, Hannah J.

AU - Brotman, Sarah M.

AU - van de Bunt, Martijn

AU - Gloyn, Anna L.

AU - Below, Jennifer E.

AU - Boehnke, Michael

AU - Bowden, Donald W.

AU - Chambers, John C.

AU - Mahajan, Anubha

AU - McCarthy, Mark I.

AU - Ng, Maggie C.Y.

AU - Petty, Lauren E.

AU - Zhang, Weihua

AU - Morris, Andrew P.

AU - Adair, Linda S.

AU - Akiyama, Masato

AU - Bian, Zheng

AU - Chan, Juliana C.N.

AU - Chang, Li Ching

AU - Chee, Miao Li

AU - Chen, Yii Der Ida

AU - Chen, Yuan Tsong

AU - Chen, Zhengming

AU - Chuang, Lee Ming

AU - Du, Shufa

AU - Gordon-Larsen, Penny

AU - Gross, Myron

AU - Guo, Xiuqing

AU - Guo, Yu

AU - Han, Sohee

AU - Howard, Annie Green

AU - Huang, Wei

AU - Hung, Yi Jen

AU - Hwang, Mi Yeong

AU - Hwu, Chii Min

AU - Ichihara, Sahoko

AU - Isono, Masato

AU - Jang, Hye Mi

AU - Jiang, Guozhi

AU - Jonas, Jost B.

AU - Kamatani, Yoichiro

AU - Katsuya, Tomohiro

AU - Kawaguchi, Takahisa

AU - Khor, Chiea Chuen

AU - Kohara, Katsuhiko

AU - Lee, Myung Shik

AU - Lee, Nanette R.

AU - Li, Liming

AU - Liu, Jianjun

AU - Luk, Andrea O.

AU - Lv, Jun

AU - Okada, Yukinori

AU - Pereira, Mark A.

AU - Sabanayagam, Charumathi

AU - Shi, Jinxiu

AU - Shin, Dong Mun

AU - So, Wing Yee

AU - Takahashi, Atsushi

AU - Tomlinson, Brian

AU - Tsai, Fuu Jen

AU - van Dam, Rob M.

AU - Xiang, Yong Bing

AU - Yamamoto, Ken

AU - Yamauchi, Toshimasa

AU - Yoon, Kyungheon

AU - Yu, Canqing

AU - Yuan, Jian Min

AU - Zhang, Liang

AU - Zheng, Wei

AU - Igase, Michiya

AU - Cho, Yoon Shin

AU - Rotter, Jerome I.

AU - Wang, Ya Xing

AU - Sheu, Wayne H.H.

AU - Yokota, Mitsuhiro

AU - Wu, Jer Yuarn

AU - Cheng, Ching Yu

AU - Wong, Tien Yin

AU - Shu, Xiao Ou

AU - Kato, Norihiro

AU - Park, Kyong Soo

AU - Tai, E. Shyong

AU - Matsuda, Fumihiko

AU - Koh, Woon Puay

AU - Ma, Ronald C.W.

AU - Maeda, Shiro

AU - Millwood, Iona Y.

AU - Lee, Juyoung

AU - Kadowaki, Takashi

AU - Walters, Robin G.

AU - Kim, Bong Jo

AU - Mohlke, Karen L.

AU - Sim, Xueling

PY - 2020/6/11

Y1 - 2020/6/11

N2 - 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.

AB - 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.

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Identification of type 2 diabetes loci in 433,540 East Asian individuals

Abstract

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