Meta-analysis identifies common variants associated with body mass index in east Asians

Wanqing Wen; Yoon Shin Cho; Wei Zheng; Rajkumar Dorajoo; Norihiro Kato; Lu Qi; Chien Hsiun Chen; Ryan J. Delahanty; Yukinori Okada; Yasuharu Tabara; Dongfeng Gu; Dingliang Zhu; Christopher A. Haiman; Zengnan Mo; Yu Tang Gao; Seang Mei Saw; Min Jin Go; Fumihiko Takeuchi; Li Ching Chang; Yoshihiro Kokubo; Jun Liang; Mei Hao; Loic Le Marchand; Yi Zhang; Yanling Hu; Tien Yin Wong; Jirong Long; Bok Ghee Han; Michiaki Kubo; Ken Yamamoto; Mei Hsin Su; Tetsuro Miki; Brian E. Henderson; Huaidong Song; Aihua Tan; Jiang He; Daniel P.K. Ng; Qiuyin Cai; Tatsuhiko Tsunoda; Fuu Jen Tsai; Naoharu Iwai; Gary K. Chen; Jiajun Shi; Jianfeng Xu; Xueling Sim; Yong Bing Xiang; Shiro Maeda; Rick T.H. Ong; Chun Li; Yusuke Nakamura; Tin Aung; Naoyuki Kamatani; Jian Jun Liu; Wei Lu; Mitsuhiro Yokota; Mark Seielstad; Cathy S.J. Fann; Jer Yuarn Wu; Jong Young Lee; Frank B. Hu; Toshihiro Tanaka; E. Shyong Tai; Xiao Ou Shu

doi:10.1038/ng.1087

Meta-analysis identifies common variants associated with body mass index in east Asians

Wanqing Wen
, Yoon Shin Cho
, Wei Zheng
, Rajkumar Dorajoo
, Norihiro Kato
, Lu Qi
, Chien Hsiun Chen
, Ryan J. Delahanty
, Yukinori Okada
, Yasuharu Tabara
, Dongfeng Gu
, Dingliang Zhu
, Christopher A. Haiman
, Zengnan Mo
, Yu Tang Gao
, Seang Mei Saw
, Min Jin Go
, Fumihiko Takeuchi
, Li Ching Chang
, Yoshihiro Kokubo

Jun Liang, Mei Hao, Loic Le Marchand, Yi Zhang, Yanling Hu, Tien Yin Wong, Jirong Long, Bok Ghee Han, Michiaki Kubo, Ken Yamamoto, Mei Hsin Su, Tetsuro Miki, Brian E. Henderson, Huaidong Song, Aihua Tan, Jiang He, Daniel P.K. Ng, Qiuyin Cai, Tatsuhiko Tsunoda, Fuu Jen Tsai, Naoharu Iwai, Gary K. Chen, Jiajun Shi, Jianfeng Xu, Xueling Sim, Yong Bing Xiang, Shiro Maeda, Rick T.H. Ong, Chun Li, Yusuke Nakamura, Tin Aung, Naoyuki Kamatani, Jian Jun Liu, Wei Lu, Mitsuhiro Yokota, Mark Seielstad, Cathy S.J. Fann, Jer Yuarn Wu, Jong Young Lee, Frank B. Hu, Toshihiro Tanaka, E. Shyong Tai, Xiao Ou Shu

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

349 被引用数 (Scopus)

抄録

Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 - 10 g8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 - 10 g7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.

本文言語	英語
ページ（範囲）	307-311
ページ数	5
ジャーナル	Nature Genetics
巻	44
号	3
DOI	https://doi.org/10.1038/ng.1087
出版ステータス	出版済み - 03-2012
外部発表	はい

UN SDG

この成果は、次の持続可能な開発目標に貢献しています

SDG 3 すべての人に健康と福祉を

All Science Journal Classification (ASJC) codes

遺伝学

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10.1038/ng.1087

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Wen, W., Cho, Y. S., Zheng, W., Dorajoo, R., Kato, N., Qi, L., Chen, C. H., Delahanty, R. J., Okada, Y., Tabara, Y., Gu, D., Zhu, D., Haiman, C. A., Mo, Z., Gao, Y. T., Saw, S. M., Go, M. J., Takeuchi, F., Chang, L. C., ... Shu, X. O. (2012). Meta-analysis identifies common variants associated with body mass index in east Asians. Nature Genetics, 44(3), 307-311. https://doi.org/10.1038/ng.1087

@article{5bc3fb44de704bfb97db38fa5a378f06,

title = "Meta-analysis identifies common variants associated with body mass index in east Asians",

abstract = "Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 - 10 g8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 - 10 g7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.",

author = "Wanqing Wen and Cho, \{Yoon Shin\} and Wei Zheng and Rajkumar Dorajoo and Norihiro Kato and Lu Qi and Chen, \{Chien Hsiun\} and Delahanty, \{Ryan J.\} and Yukinori Okada and Yasuharu Tabara and Dongfeng Gu and Dingliang Zhu and Haiman, \{Christopher A.\} and Zengnan Mo and Gao, \{Yu Tang\} and Saw, \{Seang Mei\} and Go, \{Min Jin\} and Fumihiko Takeuchi and Chang, \{Li Ching\} and Yoshihiro Kokubo and Jun Liang and Mei Hao and \{Le Marchand\}, Loic and Yi Zhang and Yanling Hu and Wong, \{Tien Yin\} and Jirong Long and Han, \{Bok Ghee\} and Michiaki Kubo and Ken Yamamoto and Su, \{Mei Hsin\} and Tetsuro Miki and Henderson, \{Brian E.\} and Huaidong Song and Aihua Tan and Jiang He and Ng, \{Daniel P.K.\} and Qiuyin Cai and Tatsuhiko Tsunoda and Tsai, \{Fuu Jen\} and Naoharu Iwai and Chen, \{Gary K.\} and Jiajun Shi and Jianfeng Xu and Xueling Sim and Xiang, \{Yong Bing\} and Shiro Maeda and Ong, \{Rick T.H.\} and Chun Li and Yusuke Nakamura and Tin Aung and Naoyuki Kamatani and Liu, \{Jian Jun\} and Wei Lu and Mitsuhiro Yokota and Mark Seielstad and Fann, \{Cathy S.J.\} and Wu, \{Jer Yuarn\} and Lee, \{Jong Young\} and Hu, \{Frank B.\} and Toshihiro Tanaka and Tai, \{E. Shyong\} and Shu, \{Xiao Ou\}",

note = "Funding Information: The Shanghai Genome Wide Associations Studies (SGWAS) would like to thank the dedicated investigators and staff members from the research teams at Vanderbilt University, the Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine and, most of all, the study participants for their contributions to this work. Genotyping assays and statistical analyses for the SGWAS were primarily supported by grants from the US National Institutes of Health (NIH; R01 CA064277, R37 CA070867, R01 CA090899, R01 CA118229, R01 CA092585 and R01 CA122756), as well as by Ingram professorship funds, Allen Foundation funds and a Vanderbilt Clinical and Translational Science Award (CTSA; 1 UL1 RR024975) from the National Center for Research Resources (NCRR) at the NIH. NIH grants provided support for the participating studies, including the Shanghai Breast Cancer Study (R01 CA064277), the Shanghai Breast Cancer Survival Study (R01 CA118229) and the Shanghai Endometrial Cancer Study (R01 CA092585). The KARE project was supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307). The Singapore Prospective Study Program (SP2) was funded through grants from the Biomedical Research Council of Singapore (BMRC; 05/1/36/19/413 and 03/1/27/18/216) and the National Medical Research Council of Singapore (NMRC; NMRC/1174/2008). E.S.T. also received support from the NMRC through a clinician scientist award (NMRC/CSA/008/2009). The Singapore Malay Eye Study (SiMES) was funded by the NMRC (NMRC/0796/2003 and NMRC/STaR/0003/2008) and the BMRC (09/1/35/19/616). The CAGE Network Studies were supported by grants for the Core Research for Evolutional Science and Technology (CREST) from the Japan Science Technology Agency, the Program for Promotion of Fundamental Studies in Health Sciences, the National Institute of Biomedical Innovation Organization (NIBIO) and the National Center for Global Health and Medicine (NCGM). L.Q. is supported by a grant from the NIH (HL071981), an American Heart Association Scientist Development Award and the Boston Obesity Nutrition Research Center (DK46200). The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by research grants from the National Heart, Lung, and Blood Institute at the NIH (HL072507, HL087263 and HL090682). SINDI was funded by grants from the BMRC (09/1/35/19/616 and 08/1/35/19/550) and the NMRC (NMRC/STaR/0003/2008). SCORM was funded by the NMRC (NMRC/0975/2005), the BMRC (06/1/21/19/466) and the Centre for Molecular Epidemiology at the National University of Singapore. The SIH was supported by the Chinese National Key Program for Basic Research (973:2004CB518603) and the Chinese National High Tech Program (863:2009AA022703). The MEC was supported by grants from the National Cancer Institute (NCI; CA063464, CA054281 and CA132839) and from the NIH Genes, Environment and Health Initiative (GEI; HG004726). Assistance with genotype cleaning for the MEC Japanese prostate cancer study was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard University, was provided by the GEI (HG04424).",

year = "2012",

month = mar,

doi = "10.1038/ng.1087",

language = "English",

volume = "44",

pages = "307--311",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "3",

}

Wen, W, Cho, YS, Zheng, W, Dorajoo, R, Kato, N, Qi, L, Chen, CH, Delahanty, RJ, Okada, Y, Tabara, Y, Gu, D, Zhu, D, Haiman, CA, Mo, Z, Gao, YT, Saw, SM, Go, MJ, Takeuchi, F, Chang, LC, Kokubo, Y, Liang, J, Hao, M, Le Marchand, L, Zhang, Y, Hu, Y, Wong, TY, Long, J, Han, BG, Kubo, M, Yamamoto, K, Su, MH, Miki, T, Henderson, BE, Song, H, Tan, A, He, J, Ng, DPK, Cai, Q, Tsunoda, T, Tsai, FJ, Iwai, N, Chen, GK, Shi, J, Xu, J, Sim, X, Xiang, YB, Maeda, S, Ong, RTH, Li, C, Nakamura, Y, Aung, T, Kamatani, N, Liu, JJ, Lu, W, Yokota, M, Seielstad, M, Fann, CSJ, Wu, JY, Lee, JY, Hu, FB, Tanaka, T, Tai, ES & Shu, XO 2012, 'Meta-analysis identifies common variants associated with body mass index in east Asians', Nature Genetics, vol. 44, no. 3, pp. 307-311. https://doi.org/10.1038/ng.1087

TY - JOUR

T1 - Meta-analysis identifies common variants associated with body mass index in east Asians

AU - Wen, Wanqing

AU - Cho, Yoon Shin

AU - Zheng, Wei

AU - Dorajoo, Rajkumar

AU - Kato, Norihiro

AU - Qi, Lu

AU - Chen, Chien Hsiun

AU - Delahanty, Ryan J.

AU - Okada, Yukinori

AU - Tabara, Yasuharu

AU - Gu, Dongfeng

AU - Zhu, Dingliang

AU - Haiman, Christopher A.

AU - Mo, Zengnan

AU - Gao, Yu Tang

AU - Saw, Seang Mei

AU - Go, Min Jin

AU - Takeuchi, Fumihiko

AU - Chang, Li Ching

AU - Kokubo, Yoshihiro

AU - Liang, Jun

AU - Hao, Mei

AU - Le Marchand, Loic

AU - Zhang, Yi

AU - Hu, Yanling

AU - Wong, Tien Yin

AU - Long, Jirong

AU - Han, Bok Ghee

AU - Kubo, Michiaki

AU - Yamamoto, Ken

AU - Su, Mei Hsin

AU - Miki, Tetsuro

AU - Henderson, Brian E.

AU - Song, Huaidong

AU - Tan, Aihua

AU - He, Jiang

AU - Ng, Daniel P.K.

AU - Cai, Qiuyin

AU - Tsunoda, Tatsuhiko

AU - Tsai, Fuu Jen

AU - Iwai, Naoharu

AU - Chen, Gary K.

AU - Shi, Jiajun

AU - Xu, Jianfeng

AU - Sim, Xueling

AU - Xiang, Yong Bing

AU - Maeda, Shiro

AU - Ong, Rick T.H.

AU - Li, Chun

AU - Nakamura, Yusuke

AU - Aung, Tin

AU - Kamatani, Naoyuki

AU - Liu, Jian Jun

AU - Lu, Wei

AU - Yokota, Mitsuhiro

AU - Seielstad, Mark

AU - Fann, Cathy S.J.

AU - Wu, Jer Yuarn

AU - Lee, Jong Young

AU - Hu, Frank B.

AU - Tanaka, Toshihiro

AU - Tai, E. Shyong

AU - Shu, Xiao Ou

N1 - Funding Information: The Shanghai Genome Wide Associations Studies (SGWAS) would like to thank the dedicated investigators and staff members from the research teams at Vanderbilt University, the Shanghai Cancer Institute and the Shanghai Institute of Preventive Medicine and, most of all, the study participants for their contributions to this work. Genotyping assays and statistical analyses for the SGWAS were primarily supported by grants from the US National Institutes of Health (NIH; R01 CA064277, R37 CA070867, R01 CA090899, R01 CA118229, R01 CA092585 and R01 CA122756), as well as by Ingram professorship funds, Allen Foundation funds and a Vanderbilt Clinical and Translational Science Award (CTSA; 1 UL1 RR024975) from the National Center for Research Resources (NCRR) at the NIH. NIH grants provided support for the participating studies, including the Shanghai Breast Cancer Study (R01 CA064277), the Shanghai Breast Cancer Survival Study (R01 CA118229) and the Shanghai Endometrial Cancer Study (R01 CA092585). The KARE project was supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307). The Singapore Prospective Study Program (SP2) was funded through grants from the Biomedical Research Council of Singapore (BMRC; 05/1/36/19/413 and 03/1/27/18/216) and the National Medical Research Council of Singapore (NMRC; NMRC/1174/2008). E.S.T. also received support from the NMRC through a clinician scientist award (NMRC/CSA/008/2009). The Singapore Malay Eye Study (SiMES) was funded by the NMRC (NMRC/0796/2003 and NMRC/STaR/0003/2008) and the BMRC (09/1/35/19/616). The CAGE Network Studies were supported by grants for the Core Research for Evolutional Science and Technology (CREST) from the Japan Science Technology Agency, the Program for Promotion of Fundamental Studies in Health Sciences, the National Institute of Biomedical Innovation Organization (NIBIO) and the National Center for Global Health and Medicine (NCGM). L.Q. is supported by a grant from the NIH (HL071981), an American Heart Association Scientist Development Award and the Boston Obesity Nutrition Research Center (DK46200). The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) is supported by research grants from the National Heart, Lung, and Blood Institute at the NIH (HL072507, HL087263 and HL090682). SINDI was funded by grants from the BMRC (09/1/35/19/616 and 08/1/35/19/550) and the NMRC (NMRC/STaR/0003/2008). SCORM was funded by the NMRC (NMRC/0975/2005), the BMRC (06/1/21/19/466) and the Centre for Molecular Epidemiology at the National University of Singapore. The SIH was supported by the Chinese National Key Program for Basic Research (973:2004CB518603) and the Chinese National High Tech Program (863:2009AA022703). The MEC was supported by grants from the National Cancer Institute (NCI; CA063464, CA054281 and CA132839) and from the NIH Genes, Environment and Health Initiative (GEI; HG004726). Assistance with genotype cleaning for the MEC Japanese prostate cancer study was provided by the Gene Environment Association Studies (GENEVA) Coordinating Center (HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Funding support for genotyping, which was performed at the Broad Institute of MIT and Harvard University, was provided by the GEI (HG04424).

PY - 2012/3

Y1 - 2012/3

N2 - Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 - 10 g8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 - 10 g7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.

AB - Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 - 10 g8), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 - 10 g7. Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations.

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UR - https://www.scopus.com/pages/publications/84862777036#tab=citedBy

U2 - 10.1038/ng.1087

DO - 10.1038/ng.1087

M3 - Article

C2 - 22344219

AN - SCOPUS:84862777036

SN - 1061-4036

VL - 44

SP - 307

EP - 311

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

Meta-analysis identifies common variants associated with body mass index in east Asians

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