Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Wanqing Wen; Wei Zheng; Yukinori Okada; Fumihiko Takeuchi; Yasuharu Tabara; Joo Yeon Hwang; Rajkumar Dorajoo; Huaixing Li; Fuu Jen Tsai; Xiaobo Yang; Jiang He; Ying Wu; Meian He; Yi Zhang; Jun Liang; Xiuqing Guo; Wayne H.uey Herng Sheu; Ryan Delahanty; Xingyi Guo; Michiaki Kubo; Ken Yamamoto; Takayoshi Ohkubo; Min J.in Go; Jian J.un Liu; Wei Gan; Ching Chu Chen; Yong Gao; Shengxu Li; Nanette R. Lee; Chen Wu; Xueya Zhou; Huaidong Song; Jie Yao; I. Te Lee; Jirong Long; Tatsuhiko Tsunoda; Koichi Akiyama; Naoyuki Takashima; Yoon S.hin Cho; Rick T.h. Ong; Ling Lu; Chien Hsiun Chen; Aihua Tan; Treva K. Rice; Linda S. Adair; Lixuan Gui; Matthew Allison; Wen Jane Lee; Qiuyin Cai; Minoru Isomura; Satoshi Umemura; Young J.in Kim; Mark Seielstad; James Hixson; Yong Bing Xiang; Masato Isono; Bong Jo Kim; Xueling Sim; Wei Lu; Toru Nabika; Juyoung Lee; Wei Yen Lim; Yu Tang Gao; Ryoichi Takayanagi; Dae Hee Kang; Tien Y.in Wong; Chao A.gnes Hsiung; I. Chien Wu; Jyh Ming J.immy Juang; Jiajun Shi; Bo Y.oul Choi; Tin Aung; Frank Hu; Mi K.yung Kim; Wei Y.en Lim; Tzung Dao Wang; Min Ho Shin; Jeannette Lee; Bu Tian Ji; Young Hoon Lee; Terri L. Young; Dong H.oon Shin; Byung Yeol Chun; Myeong Chan Cho; Bok Ghee Han; Chii Min Hwu; Themistocles L. Assimes; Devin Absher; Xiaofei Yan; Eric Kim; Jane Z. Kuo; Soonil Kwon; Kent D. Taylor; Yii Der I. Chen; Jerome I. Rotter; Lu Qi; Dingliang Zhu; Tangchun Wu; Karen L. Mohlke; Dongfeng Gu; Zengnan Mo; Jer Yuarn Wu; Xu Lin; Tetsuro Miki; E. Shyong Tai; Jong Young Lee; Norihiro Kato; Xiao Ou Shu; Toshihiro Tanaka

doi:10.1093/hmg/ddu248

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

Wanqing Wen, Wei Zheng, Yukinori Okada, Fumihiko Takeuchi, Yasuharu Tabara, Joo Yeon Hwang, Rajkumar Dorajoo, Huaixing Li, Fuu Jen Tsai, Xiaobo Yang, Jiang He, Ying Wu, Meian He, Yi Zhang, Jun Liang, Xiuqing Guo, Wayne H.uey Herng Sheu, Ryan Delahanty, Xingyi Guo, Michiaki KuboKen Yamamoto, Takayoshi Ohkubo, Min J.in Go, Jian J.un Liu, Wei Gan, Ching Chu Chen, Yong Gao, Shengxu Li, Nanette R. Lee, Chen Wu, Xueya Zhou, Huaidong Song, Jie Yao, I. Te Lee, Jirong Long, Tatsuhiko Tsunoda, Koichi Akiyama, Naoyuki Takashima, Yoon S.hin Cho, Rick T.h. Ong, Ling Lu, Chien Hsiun Chen, Aihua Tan, Treva K. Rice, Linda S. Adair, Lixuan Gui, Matthew Allison, Wen Jane Lee, Qiuyin Cai, Minoru Isomura, Satoshi Umemura, Young J.in Kim, Mark Seielstad, James Hixson, Yong Bing Xiang, Masato Isono, Bong Jo Kim, Xueling Sim, Wei Lu, Toru Nabika, Juyoung Lee, Wei Yen Lim, Yu Tang Gao, Ryoichi Takayanagi, Dae Hee Kang, Tien Y.in Wong, Chao A.gnes Hsiung, I. Chien Wu, Jyh Ming J.immy Juang, Jiajun Shi, Bo Y.oul Choi, Tin Aung, Frank Hu, Mi K.yung Kim, Wei Y.en Lim, Tzung Dao Wang, Min Ho Shin, Jeannette Lee, Bu Tian Ji, Young Hoon Lee, Terri L. Young, Dong H.oon Shin, Byung Yeol Chun, Myeong Chan Cho, Bok Ghee Han, Chii Min Hwu, Themistocles L. Assimes, Devin Absher, Xiaofei Yan, Eric Kim, Jane Z. Kuo, Soonil Kwon, Kent D. Taylor, Yii Der I. Chen, Jerome I. Rotter, Lu Qi, Dingliang Zhu, Tangchun Wu, Karen L. Mohlke, Dongfeng Gu, Zengnan Mo, Jer Yuarn Wu, Xu Lin, Tetsuro Miki, E. Shyong Tai, Jong Young Lee, Norihiro Kato, Xiao Ou Shu, Toshihiro Tanaka

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Abstract

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

Original language	English
Pages (from-to)	5492-5504
Number of pages	13
Journal	Human molecular genetics
Volume	23
Issue number	20
DOIs	https://doi.org/10.1093/hmg/ddu248
State	Published - Oct 15 2014

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10.1093/hmg/ddu248

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Wen, W., Zheng, W., Okada, Y., Takeuchi, F., Tabara, Y., Hwang, J. Y., Dorajoo, R., Li, H., Tsai, F. J., Yang, X., He, J., Wu, Y., He, M., Zhang, Y., Liang, J., Guo, X., Sheu, W. H. U. H., Delahanty, R., Guo, X., ... Tanaka, T. (2014). Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Human molecular genetics, 23(20), 5492-5504. https://doi.org/10.1093/hmg/ddu248

@article{dd62bc9856f5416a8f5f788677bf2297,

title = "Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index",

abstract = "Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.",

author = "Wanqing Wen and Wei Zheng and Yukinori Okada and Fumihiko Takeuchi and Yasuharu Tabara and Hwang, {Joo Yeon} and Rajkumar Dorajoo and Huaixing Li and Tsai, {Fuu Jen} and Xiaobo Yang and Jiang He and Ying Wu and Meian He and Yi Zhang and Jun Liang and Xiuqing Guo and Sheu, {Wayne H.uey Herng} and Ryan Delahanty and Xingyi Guo and Michiaki Kubo and Ken Yamamoto and Takayoshi Ohkubo and Go, {Min J.in} and Liu, {Jian J.un} and Wei Gan and Chen, {Ching Chu} and Yong Gao and Shengxu Li and Lee, {Nanette R.} and Chen Wu and Xueya Zhou and Huaidong Song and Jie Yao and Lee, {I. Te} and Jirong Long and Tatsuhiko Tsunoda and Koichi Akiyama and Naoyuki Takashima and Cho, {Yoon S.hin} and Ong, {Rick T.h.} and Ling Lu and Chen, {Chien Hsiun} and Aihua Tan and Rice, {Treva K.} and Adair, {Linda S.} and Lixuan Gui and Matthew Allison and Lee, {Wen Jane} and Qiuyin Cai and Minoru Isomura and Satoshi Umemura and Kim, {Young J.in} and Mark Seielstad and James Hixson and Xiang, {Yong Bing} and Masato Isono and Kim, {Bong Jo} and Xueling Sim and Wei Lu and Toru Nabika and Juyoung Lee and Lim, {Wei Yen} and Gao, {Yu Tang} and Ryoichi Takayanagi and Kang, {Dae Hee} and Wong, {Tien Y.in} and Hsiung, {Chao A.gnes} and Wu, {I. Chien} and Juang, {Jyh Ming J.immy} and Jiajun Shi and Choi, {Bo Y.oul} and Tin Aung and Frank Hu and Kim, {Mi K.yung} and Lim, {Wei Y.en} and Wang, {Tzung Dao} and Shin, {Min Ho} and Jeannette Lee and Ji, {Bu Tian} and Lee, {Young Hoon} and Young, {Terri L.} and Shin, {Dong H.oon} and Chun, {Byung Yeol} and Cho, {Myeong Chan} and Han, {Bok Ghee} and Hwu, {Chii Min} and Assimes, {Themistocles L.} and Devin Absher and Xiaofei Yan and Eric Kim and Kuo, {Jane Z.} and Soonil Kwon and Taylor, {Kent D.} and Chen, {Yii Der I.} and Rotter, {Jerome I.} and Lu Qi and Dingliang Zhu and Tangchun Wu and Mohlke, {Karen L.} and Dongfeng Gu and Zengnan Mo and Wu, {Jer Yuarn} and Xu Lin and Tetsuro Miki and Tai, {E. Shyong} and Lee, {Jong Young} and Norihiro Kato and Shu, {Xiao Ou} and Toshihiro Tanaka",

year = "2014",

month = oct,

day = "15",

doi = "10.1093/hmg/ddu248",

language = "English",

volume = "23",

pages = "5492--5504",

journal = "Human molecular genetics",

issn = "0964-6906",

number = "20",

}

Wen, W, Zheng, W, Okada, Y, Takeuchi, F, Tabara, Y, Hwang, JY, Dorajoo, R, Li, H, Tsai, FJ, Yang, X, He, J, Wu, Y, He, M, Zhang, Y, Liang, J, Guo, X, Sheu, WHUH, Delahanty, R, Guo, X, Kubo, M, Yamamoto, K, Ohkubo, T, Go, MJI, Liu, JJU, Gan, W, Chen, CC, Gao, Y, Li, S, Lee, NR, Wu, C, Zhou, X, Song, H, Yao, J, Lee, IT, Long, J, Tsunoda, T, Akiyama, K, Takashima, N, Cho, YSH, Ong, RTH, Lu, L, Chen, CH, Tan, A, Rice, TK, Adair, LS, Gui, L, Allison, M, Lee, WJ, Cai, Q, Isomura, M, Umemura, S, Kim, YJI, Seielstad, M, Hixson, J, Xiang, YB, Isono, M, Kim, BJ, Sim, X, Lu, W, Nabika, T, Lee, J, Lim, WY, Gao, YT, Takayanagi, R, Kang, DH, Wong, TYI, Hsiung, CAG, Wu, IC, Juang, JMJI, Shi, J, Choi, BYO, Aung, T, Hu, F, Kim, MKY, Lim, WYE, Wang, TD, Shin, MH, Lee, J, Ji, BT, Lee, YH, Young, TL, Shin, DHO, Chun, BY, Cho, MC, Han, BG, Hwu, CM, Assimes, TL, Absher, D, Yan, X, Kim, E, Kuo, JZ, Kwon, S, Taylor, KD, Chen, YDI, Rotter, JI, Qi, L, Zhu, D, Wu, T, Mohlke, KL, Gu, D, Mo, Z, Wu, JY, Lin, X, Miki, T, Tai, ES, Lee, JY, Kato, N, Shu, XO & Tanaka, T 2014, 'Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index', Human molecular genetics, vol. 23, no. 20, pp. 5492-5504. https://doi.org/10.1093/hmg/ddu248

TY - JOUR

T1 - Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

AU - Wen, Wanqing

AU - Zheng, Wei

AU - Okada, Yukinori

AU - Takeuchi, Fumihiko

AU - Tabara, Yasuharu

AU - Hwang, Joo Yeon

AU - Dorajoo, Rajkumar

AU - Li, Huaixing

AU - Tsai, Fuu Jen

AU - Yang, Xiaobo

AU - He, Jiang

AU - Wu, Ying

AU - He, Meian

AU - Zhang, Yi

AU - Liang, Jun

AU - Guo, Xiuqing

AU - Sheu, Wayne H.uey Herng

AU - Delahanty, Ryan

AU - Guo, Xingyi

AU - Kubo, Michiaki

AU - Yamamoto, Ken

AU - Ohkubo, Takayoshi

AU - Go, Min J.in

AU - Liu, Jian J.un

AU - Gan, Wei

AU - Chen, Ching Chu

AU - Gao, Yong

AU - Li, Shengxu

AU - Lee, Nanette R.

AU - Wu, Chen

AU - Zhou, Xueya

AU - Song, Huaidong

AU - Yao, Jie

AU - Lee, I. Te

AU - Long, Jirong

AU - Tsunoda, Tatsuhiko

AU - Akiyama, Koichi

AU - Takashima, Naoyuki

AU - Cho, Yoon S.hin

AU - Ong, Rick T.h.

AU - Lu, Ling

AU - Chen, Chien Hsiun

AU - Tan, Aihua

AU - Rice, Treva K.

AU - Adair, Linda S.

AU - Gui, Lixuan

AU - Allison, Matthew

AU - Lee, Wen Jane

AU - Cai, Qiuyin

AU - Isomura, Minoru

AU - Umemura, Satoshi

AU - Kim, Young J.in

AU - Seielstad, Mark

AU - Hixson, James

AU - Xiang, Yong Bing

AU - Isono, Masato

AU - Kim, Bong Jo

AU - Sim, Xueling

AU - Lu, Wei

AU - Nabika, Toru

AU - Lee, Juyoung

AU - Lim, Wei Yen

AU - Gao, Yu Tang

AU - Takayanagi, Ryoichi

AU - Kang, Dae Hee

AU - Wong, Tien Y.in

AU - Hsiung, Chao A.gnes

AU - Wu, I. Chien

AU - Juang, Jyh Ming J.immy

AU - Shi, Jiajun

AU - Choi, Bo Y.oul

AU - Aung, Tin

AU - Hu, Frank

AU - Kim, Mi K.yung

AU - Lim, Wei Y.en

AU - Wang, Tzung Dao

AU - Shin, Min Ho

AU - Lee, Jeannette

AU - Ji, Bu Tian

AU - Lee, Young Hoon

AU - Young, Terri L.

AU - Shin, Dong H.oon

AU - Chun, Byung Yeol

AU - Cho, Myeong Chan

AU - Han, Bok Ghee

AU - Hwu, Chii Min

AU - Assimes, Themistocles L.

AU - Absher, Devin

AU - Yan, Xiaofei

AU - Kim, Eric

AU - Kuo, Jane Z.

AU - Kwon, Soonil

AU - Taylor, Kent D.

AU - Chen, Yii Der I.

AU - Rotter, Jerome I.

AU - Qi, Lu

AU - Zhu, Dingliang

AU - Wu, Tangchun

AU - Mohlke, Karen L.

AU - Gu, Dongfeng

AU - Mo, Zengnan

AU - Wu, Jer Yuarn

AU - Lin, Xu

AU - Miki, Tetsuro

AU - Tai, E. Shyong

AU - Lee, Jong Young

AU - Kato, Norihiro

AU - Shu, Xiao Ou

AU - Tanaka, Toshihiro

PY - 2014/10/15

Y1 - 2014/10/15

N2 - Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

AB - Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

UR - http://www.scopus.com/inward/record.url?scp=84964314917&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddu248

DO - 10.1093/hmg/ddu248

M3 - Article

C2 - 24861553

AN - SCOPUS:84964314917

SN - 0964-6906

VL - 23

SP - 5492

EP - 5504

JO - Human molecular genetics

JF - Human molecular genetics

IS - 20

ER -

Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index

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