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

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 s... Full description

Journal Title: Human Molecular Genetics 2014, Vol. 23(20), pp.5492-5504
Main Author: Wen, Wanqing
Other Authors: Zheng, Wei , Okada, Yukinori , Takeuchi, Fumihiko , Tabara, Yasuharu , Hwang, Joo - Yeon , Dorajoo, Rajkumar , Li, Huaixing , Tsai, Fuu - Jen , Yang, Xiaobo , He, Jiang , Wu, Ying , He, Meian , Zhang, Yi , Liang, Jun , Guo, Xiuqing , Sheu, Wayne Huey - Herng , Delahanty, Ryan , Guo, Xingyi , Kubo, Michiaki , Yamamoto, Ken , Ohkubo, Takayoshi , Go, Min Jin , Liu, Jian Jun , Gan, Wei , Chen, Ching - Chu , Gao, Yong , Li, Shengxu , Lee, Nanette R , Wu, Chen , Zhou, Xueya , Song, Huaidong , Yao, Jie , Lee, I - Te , Long, Jirong , Tsunoda, Tatsuhiko , Akiyama, Koichi , Takashima, Naoyuki , Cho, Yoon Shin , Ong, Rick Th , Lu, Ling , Chen, Chien - Hsiun , Tan, Aihua , Rice, Treva K , Adair, Linda S , Gui, Lixuan , Allison, Matthew , Lee, Wen - Jane , Cai, Qiuyin , Isomura, Minoru , Umemura, Satoshi , Kim, Young Jin , Seielstad, Mark , Hixson, James , Xiang, Yong - Bing , Isono, Masato , Kim, Bong - Jo , Sim, Xueling , Lu, Wei , Nabika, Toru , Lee, Juyoung , Lim, Wei - Yen , Gao, Yu - Tang , Takayanagi, Ryoichi , Kang, Dae - Hee , Wong, Tien Yin , Hsiung, Chao Agnes , Wu, I - Chien , Juang, Jyh - Ming Jimmy , Shi, Jiajun , Choi, Bo Youl , Aung, Tin , Hu, Frank , Kim, Mi Kyung , Lim, Wei Yen , Wang, Tzung - Dao , Shin, Min - Ho , Lee, Jeannette , Ji, Bu - Tian , Lee, Young - Hoon , Young, Terri L , Shin, Dong Hoon , Chun, Byung - Yeol , Cho, Myeong - Chan , Han, Bok - Ghee , Hwu, Chii - Min , Assimes, Themistocles L , Absher, Devin , Yan, Xiaofei , Kim, Eric , Kuo, Jane Z , Kwon, Soonil , Taylor, Kent D , Chen, Yii - Der I , Rotter, Jerome I , Qi, Lu , Zhu, Dingliang , Wu, Tangchun , Mohlke, Karen L , Gu, Dongfeng , Mo, Zengnan , Wu, Jer - Yuarn , Lin, Xu , Miki, Tetsuro , Tai, E. Shyong , Lee, Jong - Young , Kato, Norihiro , Shu, Xiao - Ou , Tanaka, Toshihiro
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ID: ISSN: 0964-6906 ; E-ISSN: 1460-2083 ; DOI: 10.1093/hmg/ddu248
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recordid: oxford10.1093/hmg/ddu248
title: Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
format: Article
creator:
  • Wen, Wanqing
  • Zheng, Wei
  • Okada, Yukinori
  • Takeuchi, Fumihiko
  • Tabara, Yasuharu
  • Hwang, Joo - Yeon
  • Dorajoo, Rajkumar
  • Li, Huaixing
  • Tsai, Fuu - Jen
  • Yang, Xiaobo
  • He, Jiang
  • Wu, Ying
  • He, Meian
  • Zhang, Yi
  • Liang, Jun
  • Guo, Xiuqing
  • Sheu, Wayne Huey - Herng
  • Delahanty, Ryan
  • Guo, Xingyi
  • Kubo, Michiaki
  • Yamamoto, Ken
  • Ohkubo, Takayoshi
  • Go, Min Jin
  • Liu, Jian Jun
  • Gan, Wei
  • Chen, Ching - Chu
  • Gao, Yong
  • Li, Shengxu
  • Lee, Nanette R
  • Wu, Chen
  • Zhou, Xueya
  • Song, Huaidong
  • Yao, Jie
  • Lee, I - Te
  • Long, Jirong
  • Tsunoda, Tatsuhiko
  • Akiyama, Koichi
  • Takashima, Naoyuki
  • Cho, Yoon Shin
  • Ong, Rick Th
  • Lu, Ling
  • Chen, Chien - Hsiun
  • Tan, Aihua
  • Rice, Treva K
  • Adair, Linda S
  • Gui, Lixuan
  • Allison, Matthew
  • Lee, Wen - Jane
  • Cai, Qiuyin
  • Isomura, Minoru
  • Umemura, Satoshi
  • Kim, Young Jin
  • Seielstad, Mark
  • Hixson, James
  • Xiang, Yong - Bing
  • Isono, Masato
  • Kim, Bong - Jo
  • Sim, Xueling
  • Lu, Wei
  • Nabika, Toru
  • Lee, Juyoung
  • Lim, Wei - Yen
  • Gao, Yu - Tang
  • Takayanagi, Ryoichi
  • Kang, Dae - Hee
  • Wong, Tien Yin
  • Hsiung, Chao Agnes
  • Wu, I - Chien
  • Juang, Jyh - Ming Jimmy
  • Shi, Jiajun
  • Choi, Bo Youl
  • Aung, Tin
  • Hu, Frank
  • Kim, Mi Kyung
  • Lim, Wei Yen
  • Wang, Tzung - Dao
  • Shin, Min - Ho
  • Lee, Jeannette
  • Ji, Bu - Tian
  • Lee, Young - Hoon
  • Young, Terri L
  • Shin, Dong Hoon
  • Chun, Byung - Yeol
  • Cho, Myeong - Chan
  • Han, Bok - Ghee
  • Hwu, Chii - Min
  • Assimes, Themistocles L
  • Absher, Devin
  • Yan, Xiaofei
  • Kim, Eric
  • Kuo, Jane Z
  • Kwon, Soonil
  • Taylor, Kent D
  • Chen, Yii - Der I
  • Rotter, Jerome I
  • Qi, Lu
  • Zhu, Dingliang
  • Wu, Tangchun
  • Mohlke, Karen L
  • Gu, Dongfeng
  • Mo, Zengnan
  • Wu, Jer - Yuarn
  • Lin, Xu
  • Miki, Tetsuro
  • Tai, E. Shyong
  • Lee, Jong - Young
  • Kato, Norihiro
  • Shu, Xiao - Ou
  • Tanaka, Toshihiro
subjects:
  • Medicine
  • Biology
ispartof: Human Molecular Genetics, 2014, Vol. 23(20), pp.5492-5504
description: 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.
language:
source:
identifier: ISSN: 0964-6906 ; E-ISSN: 1460-2083 ; DOI: 10.1093/hmg/ddu248
fulltext: fulltext
issn:
  • 0964-6906
  • 09646906
  • 1460-2083
  • 14602083
url: Link


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titleMeta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
creatorWen, Wanqing ; Zheng, Wei ; Okada, Yukinori ; Takeuchi, Fumihiko ; Tabara, Yasuharu ; Hwang, Joo - Yeon ; Dorajoo, Rajkumar ; Li, Huaixing ; Tsai, Fuu - Jen ; Yang, Xiaobo ; He, Jiang ; Wu, Ying ; He, Meian ; Zhang, Yi ; Liang, Jun ; Guo, Xiuqing ; Sheu, Wayne Huey - Herng ; Delahanty, Ryan ; Guo, Xingyi ; Kubo, Michiaki ; Yamamoto, Ken ; Ohkubo, Takayoshi ; Go, Min Jin ; Liu, Jian Jun ; Gan, Wei ; Chen, Ching - Chu ; Gao, Yong ; Li, Shengxu ; Lee, Nanette R ; Wu, Chen ; Zhou, Xueya ; Song, Huaidong ; Yao, Jie ; Lee, I - Te ; Long, Jirong ; Tsunoda, Tatsuhiko ; Akiyama, Koichi ; Takashima, Naoyuki ; Cho, Yoon Shin ; Ong, Rick Th ; Lu, Ling ; Chen, Chien - Hsiun ; Tan, Aihua ; Rice, Treva K ; Adair, Linda S ; Gui, Lixuan ; Allison, Matthew ; Lee, Wen - Jane ; Cai, Qiuyin ; Isomura, Minoru ; Umemura, Satoshi ; Kim, Young Jin ; Seielstad, Mark ; Hixson, James ; Xiang, Yong - Bing ; Isono, Masato ; Kim, Bong - Jo ; Sim, Xueling ; Lu, Wei ; Nabika, Toru ; Lee, Juyoung ; Lim, Wei - Yen ; Gao, Yu - Tang ; Takayanagi, Ryoichi ; Kang, Dae - Hee ; Wong, Tien Yin ; Hsiung, Chao Agnes ; Wu, I - Chien ; Juang, Jyh - Ming Jimmy ; Shi, Jiajun ; Choi, Bo Youl ; Aung, Tin ; Hu, Frank ; Kim, Mi Kyung ; Lim, Wei Yen ; Wang, Tzung - Dao ; Shin, Min - Ho ; Lee, Jeannette ; Ji, Bu - Tian ; Lee, Young - Hoon ; Young, Terri L ; Shin, Dong Hoon ; Chun, Byung - Yeol ; Cho, Myeong - Chan ; Han, Bok - Ghee ; Hwu, Chii - Min ; Assimes, Themistocles L ; Absher, Devin ; Yan, Xiaofei ; Kim, Eric ; Kuo, Jane Z ; Kwon, Soonil ; Taylor, Kent D ; Chen, Yii - Der I ; Rotter, Jerome I ; Qi, Lu ; Zhu, Dingliang ; Wu, Tangchun ; Mohlke, Karen L ; Gu, Dongfeng ; Mo, Zengnan ; Wu, Jer - Yuarn ; Lin, Xu ; Miki, Tetsuro ; Tai, E. Shyong ; Lee, Jong - Young ; Kato, Norihiro ; Shu, Xiao - Ou ; Tanaka, Toshihiro
ispartofHuman Molecular Genetics, 2014, Vol. 23(20), pp.5492-5504
identifier
descriptionRecent 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.
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titleMeta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
descriptionRecent 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.
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titleMeta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
authorWen, Wanqing ; Zheng, Wei ; Okada, Yukinori ; Takeuchi, Fumihiko ; Tabara, Yasuharu ; Hwang, Joo - Yeon ; Dorajoo, Rajkumar ; Li, Huaixing ; Tsai, Fuu - Jen ; Yang, Xiaobo ; He, Jiang ; Wu, Ying ; He, Meian ; Zhang, Yi ; Liang, Jun ; Guo, Xiuqing ; Sheu, Wayne Huey - Herng ; Delahanty, Ryan ; Guo, Xingyi ; Kubo, Michiaki ; Yamamoto, Ken ; Ohkubo, Takayoshi ; Go, Min Jin ; Liu, Jian Jun ; Gan, Wei ; Chen, Ching - Chu ; Gao, Yong ; Li, Shengxu ; Lee, Nanette R ; Wu, Chen ; Zhou, Xueya ; Song, Huaidong ; Yao, Jie ; Lee, I - Te ; Long, Jirong ; Tsunoda, Tatsuhiko ; Akiyama, Koichi ; Takashima, Naoyuki ; Cho, Yoon Shin ; Ong, Rick Th ; Lu, Ling ; Chen, Chien - Hsiun ; Tan, Aihua ; Rice, Treva K ; Adair, Linda S ; Gui, Lixuan ; Allison, Matthew ; Lee, Wen - Jane ; Cai, Qiuyin ; Isomura, Minoru ; Umemura, Satoshi ; Kim, Young Jin ; Seielstad, Mark ; Hixson, James ; Xiang, Yong - Bing ; Isono, Masato ; Kim, Bong - Jo ; Sim, Xueling ; Lu, Wei ; Nabika, Toru ; Lee, Juyoung ; Lim, Wei - Yen ; Gao, Yu - Tang ; Takayanagi, Ryoichi ; Kang, Dae - Hee ; Wong, Tien Yin ; Hsiung, Chao Agnes ; Wu, I - Chien ; Juang, Jyh - Ming Jimmy ; Shi, Jiajun ; Choi, Bo Youl ; Aung, Tin ; Hu, Frank ; Kim, Mi Kyung ; Lim, Wei Yen ; Wang, Tzung - Dao ; Shin, Min - Ho ; Lee, Jeannette ; Ji, Bu - Tian ; Lee, Young - Hoon ; Young, Terri L ; Shin, Dong Hoon ; Chun, Byung - Yeol ; Cho, Myeong - Chan ; Han, Bok - Ghee ; Hwu, Chii - Min ; Assimes, Themistocles L ; Absher, Devin ; Yan, Xiaofei ; Kim, Eric ; Kuo, Jane Z ; Kwon, Soonil ; Taylor, Kent D ; Chen, Yii - Der I ; Rotter, Jerome I ; Qi, Lu ; Zhu, Dingliang ; Wu, Tangchun ; Mohlke, Karen L ; Gu, Dongfeng ; Mo, Zengnan ; Wu, Jer - Yuarn ; Lin, Xu ; Miki, Tetsuro ; Tai, E. Shyong ; Lee, Jong - Young ; Kato, Norihiro ; Shu, Xiao - Ou ; Tanaka, Toshihiro
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33Lee, I-Te
34Long, Jirong
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36Akiyama, Koichi
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45Gui, Lixuan
46Allison, Matthew
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49Isomura, Minoru
50Umemura, Satoshi
51Kim, Young Jin
52Seielstad, Mark
53Hixson, James
54Xiang, Yong-Bing
55Isono, Masato
56Kim, Bong-Jo
57Sim, Xueling
58Lu, Wei
59Nabika, Toru
60Lee, Juyoung
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62Gao, Yu-Tang
63Takayanagi, Ryoichi
64Kang, Dae-Hee
65Wong, Tien Yin
66Hsiung, Chao Agnes
67Wu, I-Chien
68Juang, Jyh-Ming Jimmy
69Shi, Jiajun
70Choi, Bo Youl
71Aung, Tin
72Hu, Frank
73Kim, Mi Kyung
74Lim, Wei Yen
75Wang, Tzung-Dao
76Shin, Min-Ho
77Lee, Jeannette
78Ji, Bu-Tian
79Lee, Young-Hoon
80Young, Terri L.
81Shin, Dong Hoon
82Chun, Byung-Yeol
83Cho, Myeong-Chan
84Han, Bok-Ghee
85Hwu, Chii-Min
86Assimes, Themistocles L.
87Absher, Devin
88Yan, Xiaofei
89Kim, Eric
90Kuo, Jane Z.
91Kwon, Soonil
92Taylor, Kent D.
93Chen, Yii-Der I.
94Rotter, Jerome I.
95Qi, Lu
96Zhu, Dingliang
97Wu, Tangchun
98Mohlke, Karen L.
99Gu, Dongfeng
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atitleMeta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index
jtitleHuman Molecular Genetics
risdate201410
volume23
issue20
spage5492
epage5504
pages5492-5504
issn0964-6906
eissn1460-2083
formatjournal
genrearticle
ristypeJOUR
abstractRecent 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.
pubOxford University Press
doi10.1093/hmg/ddu248
date2014-10