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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(-8)), 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(-7). 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.

SUBMITTER: Wen W

PROVIDER: S-EPMC3288728 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Wen Wanqing W Cho Yoon-Shin YS Zheng Wei W Dorajoo Rajkumar R Kato Norihiro N Qi Lu L Chen Chien-Hsiun CH Delahanty Ryan J RJ Okada Yukinori Y Tabara Yasuharu Y Gu Dongfeng D Zhu Dingliang D Haiman Christopher A CA Mo Zengnan Z Gao Yu-Tang YT Saw Seang-Mei SM Go Min-Jin MJ Takeuchi Fumihiko F Chang Li-Ching LC Kokubo Yoshihiro Y Liang Jun J Hao Mei M Le Marchand Loïc L Zhang Yi Y Hu Yanling Y Wong Tien-Yin TY Long Jirong J Han Bok-Ghee BG Kubo Michiaki M Yamamoto Ken K Su Mei-Hsin MH Miki Tetsuro T Henderson Brian E BE Song Huaidong H Tan Aihua A He Jiang J Ng Daniel P-K DP Cai Qiuyin Q Tsunoda Tatsuhiko T Tsai Fuu-Jen FJ Iwai Naoharu N Chen Gary K GK Shi Jiajun J Xu Jianfeng J Sim Xueling X Xiang Yong-Bing YB Maeda Shiro S Ong Rick T H RT Li Chun C Nakamura Yusuke Y Aung Tin T Kamatani Naoyuki N Liu Jian-Jun JJ Lu Wei W Yokota Mitsuhiro M Seielstad Mark M Fann Cathy S J CS Wu Jer-Yuarn JY Lee Jong-Young JY Hu Frank B FB Tanaka Toshihiro T Tai E Shyong ES Shu Xiao-Ou XO

Nature genetics 20120219 3

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 ...[more]

PMID: 22344219

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Project description:ObjectiveTo evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians.DesignPooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability.SettingGeneral populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh).Participants1,124,897 men and women (mean age 53.4 years at baseline).Main outcome measuresRisk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes.Results49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12).ConclusionsBody mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

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

Publications

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

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