Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Yoon Shin Cho; Chien-Hsiun Chen; Cheng Hu; Jirong Long; Rick Twee Hee Ong; Xueling Sim; Fumihiko Takeuchi; Ying Wu; Min Jin Go; Toshimasa Yamauchi; Yi-Cheng Chang; Soo Heon Kwak; Ronald C W Ma; Ken Yamamoto; Linda S Adair; Tin Aung; Qiuyin Cai; Li-Ching Chang; Yuan-Tsong Chen; Yutang Gao; Frank B Hu; Hyung-Lae Kim; Sangsoo Kim; Young Jin Kim; Jeannette Jen-Mai Lee; Nanette R Lee; Yun Li; Jian Jun Liu; Wei Lu; Jiro Nakamura; Eitaro Nakashima; Daniel Peng-Keat Ng; Wan Ting Tay; Fuu-Jen Tsai; Tien Yin Wong; Mitsuhiro Yokota; Wei Zheng; Rong Zhang; Congrong Wang; Wing Yee So; Keizo Ohnaka; Hiroshi Ikegami; Kazuo Hara; Young Min Cho; Nam H Cho; Tien-Jyun Chang; Yuqian Bao; Åsa K Hedman; Andrew P Morris; DIAGRAM Consortium; Torben Jørgensen

doi:10.1038/ng.1019

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Yoon Shin Cho, Chien-Hsiun Chen, Cheng Hu, Jirong Long, Rick Twee Hee Ong, Xueling Sim, Fumihiko Takeuchi, Ying Wu, Min Jin Go, Toshimasa Yamauchi, Yi-Cheng Chang, Soo Heon Kwak, Ronald C W Ma, Ken Yamamoto, Linda S Adair, Tin Aung, Qiuyin Cai, Li-Ching Chang, Yuan-Tsong Chen, Yutang GaoFrank B Hu, Hyung-Lae Kim, Sangsoo Kim, Young Jin Kim, Jeannette Jen-Mai Lee, Nanette R Lee, Yun Li, Jian Jun Liu, Wei Lu, Jiro Nakamura, Eitaro Nakashima, Daniel Peng-Keat Ng, Wan Ting Tay, Fuu-Jen Tsai, Tien Yin Wong, Mitsuhiro Yokota, Wei Zheng, Rong Zhang, Congrong Wang, Wing Yee So, Keizo Ohnaka, Hiroshi Ikegami, Kazuo Hara, Young Min Cho, Nam H Cho, Tien-Jyun Chang, Yuqian Bao, Åsa K Hedman, Andrew P Morris, DIAGRAM Consortium, Torben Jørgensen

Department of Public Health

441 Citations (Scopus)

Abstract

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

Original language	English
Journal	Nature Genetics
Volume	44
Issue number	1
Pages (from-to)	67-72
Number of pages	6
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.1019
Publication status	Published - Jan 2012

Keywords

Adult
Asian Continental Ancestry Group
Blood Glucose
Case-Control Studies
Chromosome Mapping
Diabetes Mellitus, Type 2
Far East
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Polymorphism, Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ng.1019

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Cho, Y. S., Chen, C-H., Hu, C., Long, J., Ong, R. T. H., Sim, X., Takeuchi, F., Wu, Y., Go, M. J., Yamauchi, T., Chang, Y-C., Kwak, S. H., Ma, R. C. W., Yamamoto, K., Adair, L. S., Aung, T., Cai, Q., Chang, L-C., Chen, Y-T., ... Jørgensen, T. (2012). Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nature Genetics, 44(1), 67-72. https://doi.org/10.1038/ng.1019

Cho, YS, Chen, C-H, Hu, C, Long, J, Ong, RTH, Sim, X, Takeuchi, F, Wu, Y, Go, MJ, Yamauchi, T, Chang, Y-C, Kwak, SH, Ma, RCW, Yamamoto, K, Adair, LS, Aung, T, Cai, Q, Chang, L-C, Chen, Y-T, Gao, Y, Hu, FB, Kim, H-L, Kim, S, Kim, YJ, Lee, JJ-M, Lee, NR, Li, Y, Liu, JJ, Lu, W, Nakamura, J, Nakashima, E, Ng, DP-K, Tay, WT, Tsai, F-J, Wong, TY, Yokota, M, Zheng, W, Zhang, R, Wang, C, So, WY, Ohnaka, K, Ikegami, H, Hara, K, Cho, YM, Cho, NH, Chang, T-J, Bao, Y, Hedman, ÅK, Morris, AP, DIAGRAM Consortium & Jørgensen, T 2012, 'Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians', Nature Genetics, vol. 44, no. 1, pp. 67-72. https://doi.org/10.1038/ng.1019

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title = "Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians",

abstract = "We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.",

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author = "Cho, {Yoon Shin} and Chien-Hsiun Chen and Cheng Hu and Jirong Long and Ong, {Rick Twee Hee} and Xueling Sim and Fumihiko Takeuchi and Ying Wu and Go, {Min Jin} and Toshimasa Yamauchi and Yi-Cheng Chang and Kwak, {Soo Heon} and Ma, {Ronald C W} and Ken Yamamoto and Adair, {Linda S} and Tin Aung and Qiuyin Cai and Li-Ching Chang and Yuan-Tsong Chen and Yutang Gao and Hu, {Frank B} and Hyung-Lae Kim and Sangsoo Kim and Kim, {Young Jin} and Lee, {Jeannette Jen-Mai} and Lee, {Nanette R} and Yun Li and Liu, {Jian Jun} and Wei Lu and Jiro Nakamura and Eitaro Nakashima and Ng, {Daniel Peng-Keat} and Tay, {Wan Ting} and Fuu-Jen Tsai and Wong, {Tien Yin} and Mitsuhiro Yokota and Wei Zheng and Rong Zhang and Congrong Wang and So, {Wing Yee} and Keizo Ohnaka and Hiroshi Ikegami and Kazuo Hara and Cho, {Young Min} and Cho, {Nam H} and Tien-Jyun Chang and Yuqian Bao and Hedman, {{\AA}sa K} and Morris, {Andrew P} and {DIAGRAM Consortium} and Torben J{\o}rgensen",

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AU - Cho, Yoon Shin

AU - Chen, Chien-Hsiun

AU - Hu, Cheng

AU - Long, Jirong

AU - Ong, Rick Twee Hee

AU - Sim, Xueling

AU - Takeuchi, Fumihiko

AU - Wu, Ying

AU - Go, Min Jin

AU - Yamauchi, Toshimasa

AU - Chang, Yi-Cheng

AU - Kwak, Soo Heon

AU - Ma, Ronald C W

AU - Yamamoto, Ken

AU - Adair, Linda S

AU - Aung, Tin

AU - Cai, Qiuyin

AU - Chang, Li-Ching

AU - Chen, Yuan-Tsong

AU - Gao, Yutang

AU - Hu, Frank B

AU - Kim, Hyung-Lae

AU - Kim, Sangsoo

AU - Kim, Young Jin

AU - Lee, Jeannette Jen-Mai

AU - Lee, Nanette R

AU - Li, Yun

AU - Liu, Jian Jun

AU - Lu, Wei

AU - Nakamura, Jiro

AU - Nakashima, Eitaro

AU - Ng, Daniel Peng-Keat

AU - Tay, Wan Ting

AU - Tsai, Fuu-Jen

AU - Wong, Tien Yin

AU - Yokota, Mitsuhiro

AU - Zheng, Wei

AU - Zhang, Rong

AU - Wang, Congrong

AU - So, Wing Yee

AU - Ohnaka, Keizo

AU - Ikegami, Hiroshi

AU - Hara, Kazuo

AU - Cho, Young Min

AU - Cho, Nam H

AU - Chang, Tien-Jyun

AU - Bao, Yuqian

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AU - Morris, Andrew P

AU - DIAGRAM Consortium

AU - Jørgensen, Torben

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AB - We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

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KW - Asian Continental Ancestry Group

KW - Blood Glucose

KW - Case-Control Studies

KW - Chromosome Mapping

KW - Diabetes Mellitus, Type 2

KW - Far East

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Polymorphism, Single Nucleotide

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JO - Nature: New biology

JF - Nature: New biology

IS - 1

ER -

Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Abstract

Keywords

UN SDGs

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