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

Hum. Mol. Genet.2014 Oct 15;23(20):5492-504. Epub 2014 May 26
Wanqing Wen 1 , Wei Zheng 1 , Yukinori Okada 2 , Fumihiko Takeuchi 3 , Yasuharu Tabara 4 , Joo-Yeon Hwang 5 , Rajkumar Dorajoo 6 , Huaixing Li 7 , Fuu-Jen Tsai 8 , Xiaobo Yang 9 , Jiang He 10 , Ying Wu 11 , Meian He 12 , Yi Zhang 13 , Jun Liang 14 , Xiuqing Guo 15 , Wayne Huey-Herng Sheu 16 , Ryan Delahanty 1 , Xingyi Guo 1 , Michiaki Kubo 17 , Ken Yamamoto 18 , Takayoshi Ohkubo 19 , Min Jin Go 5 , Jian Jun Liu 20 , Wei Gan 7 , Ching-Chu Chen 21 , Yong Gao 22 , Shengxu Li 10 , Nanette R Lee 23 , Chen Wu 24 , Xueya Zhou 25 , Huaidong Song 26 , Jie Yao 15 , I-Te Lee 27 , Jirong Long 1 , Tatsuhiko Tsunoda 28 , Koichi Akiyama 3 , Naoyuki Takashima 29 , Yoon Shin Cho 30 , Rick Th Ong 31 , Ling Lu 7 , Chien-Hsiun Chen 32 , Aihua Tan 33 , Treva K Rice 34 , Linda S Adair 35 , Lixuan Gui 12 , Matthew Allison 36 , Wen-Jane Lee 37 , Qiuyin Cai 1 , Minoru Isomura 38 , Satoshi Umemura 39 , Young Jin Kim 5 , Mark Seielstad 40 , James Hixson 41 , Yong-Bing Xiang 42 , Masato Isono 3 , Bong-Jo Kim 5 , Xueling Sim 43 , Wei Lu 44 , Toru Nabika 38 , Juyoung Lee 5 , Wei-Yen Lim 45 , Yu-Tang Gao 46 , Ryoichi Takayanagi 47 , Dae-Hee Kang 48 , Tien Yin Wong 49 , Chao Agnes Hsiung 50 , I-Chien Wu 50 , Jyh-Ming Jimmy Juang 51 , Jiajun Shi 1 , Bo Youl Choi 52 , Tin Aung 49 , Frank Hu 53 , Mi Kyung Kim 52 , Wei Yen Lim 45 , Tzung-Dao Wang 51 , Min-Ho Shin 54 , Jeannette Lee 45 , Bu-Tian Ji 55 , Young-Hoon Lee 56 , Terri L Young 57 , Dong Hoon Shin 58 , Byung-Yeol Chun 59 , Myeong-Chan Cho 60 , Bok-Ghee Han 5 , Chii-Min Hwu 61 , Themistocles L Assimes 62 , Devin Absher 63 , Xiaofei Yan 15 , Eric Kim 15 , Jane Z Kuo 64 , Soonil Kwon 15 , Kent D Taylor 15 , Yii-Der I Chen 15 , Jerome I Rotter 15 , Lu Qi 65 , Dingliang Zhu 13 , Tangchun Wu 12 , Karen L Mohlke 11 , Dongfeng Gu 66 , Zengnan Mo 67 , Jer-Yuarn Wu 32 , Xu Lin 7 , Tetsuro Miki 68 , E Shyong Tai 69 , Jong-Young Lee 5 , Norihiro Kato 3 , Xiao-Ou Shu 70 , Toshihiro Tanaka 71
Wanqing Wen 1 , Wei Zheng 1 , Yukinori Okada 2 , Fumihiko Takeuchi 3 , Yasuharu Tabara 4 , Joo-Yeon Hwang 5 , Rajkumar Dorajoo 6 , Huaixing Li 7 , Fuu-Jen Tsai 8 , Xiaobo Yang 9 , Jiang He 10 , Ying Wu 11 , Meian He 12 , Yi Zhang 13 , Jun Liang 14 , Xiuqing Guo 15 , Wayne Huey-Herng Sheu 16 , Ryan Delahanty 1 , Xingyi Guo 1 , Michiaki Kubo 17 , Ken Yamamoto 18 , Takayoshi Ohkubo 19 , Min Jin Go 5 , Jian Jun Liu 20 , Wei Gan 7 , Ching-Chu Chen 21 , Yong Gao 22 , Shengxu Li 10 , Nanette R Lee 23 , Chen Wu 24 , Xueya Zhou 25 , Huaidong Song 26 , Jie Yao 15 , I-Te Lee 27 , Jirong Long 1 , Tatsuhiko Tsunoda 28 , Koichi Akiyama 3 , Naoyuki Takashima 29 , Yoon Shin Cho 30 , Rick Th Ong 31 , Ling Lu 7 , Chien-Hsiun Chen 32 , Aihua Tan 33 , Treva K Rice 34 , Linda S Adair 35 , Lixuan Gui 12 , Matthew Allison 36 , Wen-Jane Lee 37 , Qiuyin Cai 1 , Minoru Isomura 38 , Satoshi Umemura 39 , Young Jin Kim 5 , Mark Seielstad 40 , James Hixson 41 , Yong-Bing Xiang 42 , Masato Isono 3 , Bong-Jo Kim 5 , Xueling Sim 43 , Wei Lu 44 , Toru Nabika 38 , Juyoung Lee 5 , Wei-Yen Lim 45 , Yu-Tang Gao 46 , Ryoichi Takayanagi 47 , Dae-Hee Kang 48 , Tien Yin Wong 49 , Chao Agnes Hsiung 50 , I-Chien Wu 50 , Jyh-Ming Jimmy Juang 51 , Jiajun Shi 1 , Bo Youl Choi 52 , Tin Aung 49 , Frank Hu 53 , Mi Kyung Kim 52 , Wei Yen Lim 45 , Tzung-Dao Wang 51 , Min-Ho Shin 54 , Jeannette Lee 45 , Bu-Tian Ji 55 , Young-Hoon Lee 56 , Terri L Young 57 , Dong Hoon Shin 58 , Byung-Yeol Chun 59 , Myeong-Chan Cho 60 , Bok-Ghee Han 5 , Chii-Min Hwu 61 , Themistocles L Assimes 62 , Devin Absher 63 , Xiaofei Yan 15 , Eric Kim 15 , Jane Z Kuo 64 , Soonil Kwon 15 , Kent D Taylor 15 , Yii-Der I Chen 15 , Jerome I Rotter 15 , Lu Qi 65 , Dingliang Zhu 13 , Tangchun Wu 12 , Karen L Mohlke 11 , Dongfeng Gu 66 , Zengnan Mo 67 , Jer-Yuarn Wu 32 , Xu Lin 7 , Tetsuro Miki 68 , E Shyong Tai 69 , Jong-Young Lee 5 , Norihiro Kato 3 , Xiao-Ou Shu 70 , Toshihiro Tanaka 71
+ et al

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Author information
  • 1 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA.
  • 2 Laboratory for Statistical Analysis, Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
  • 3 Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • 4 Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
  • 5 Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
  • 6 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore, Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
  • 7 Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.
  • 8 School of Chinese Medicine, Department of Medical Genetics, Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
  • 9 Department of Occupational Health and Environmental Health, School of Public Health, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 10 Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
  • 11 Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • 12 Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
  • 13 State Key Laboratory of Medical Genetics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai Institute of Hypertension, Shanghai, China.
  • 14 Department of Endocrinology, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical College, Affiliated Hospital of Southeast University, Xuzhou, Jiangsu 221009, China.
  • 15 Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Institute for Translational Genomics and Populations Sciences, Torrance, CA, USA.
  • 16 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, National Defense Medical Center, College of Medicine, Taipei, Taiwan, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
  • 17 Laboratory for Genotyping Development.
  • 18 Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
  • 19 Department of Planning for Drug Development and Clinical Evaluation, Tohoku University Graduate School of Pharmaceutical Sciences, Sendai, Japan, Department of Health Science, Shiga University of Medical Science, Otsu, Japan.
  • 20 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
  • 21 School of Chinese Medicine, Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan.
  • 22 Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China, College of General Practice, Guangxi Medical University, Nanning, Guangxi, China.
  • 23 USC-Office of Population Studies Foundation, Inc., University of San Carlos, Cebu, Philippines.
  • 24 State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • 25 Bioinformatics Division, Tsinghua National Laboratory of Information Science and Technology, Beijing, China.
  • 26 State Key Laboratory of Medical Genomics, Ruijin Hospital, Molecular Medical Center, Shanghai Institute of Endocrinology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 27 Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan, Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan.
  • 28 Laboratory for Medical Science Mathematics.
  • 29 Department of Health Science, Shiga University of Medical Science, Otsu, Japan.
  • 30 Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea, Department of Biomedical Science, Hallym University, Gangwon-do, Republic of Korea.
  • 31 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore, NUS Graduate School for Integrative Science and Engineering, Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
  • 32 School of Chinese Medicine, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • 33 Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China.
  • 34 Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
  • 35 Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.
  • 36 Department of Family and Preventive Medicine.
  • 37 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Department of Social Work, Tunghai University, Taichung, Taiwan.
  • 38 Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
  • 39 Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, Yokohama, Japan.
  • 40 Institute of Human Genetics, University of California, San Francisco, USA.
  • 41 Human Genetics Center, University of Texas School of Public Health, Houston, TX, USA.
  • 42 Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 43 Centre for Molecular Epidemiology, National University of Singapore, Singapore, Singapore.
  • 44 Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.
  • 45 Saw Swee Hock School of Public Health.
  • 46 Department of Epidemiology, Shanghai Cancer Institute, Shanghai Jiao Tong University, Shanghai, China.
  • 47 Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
  • 48 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 49 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore, Department of Ophthalmology, Yong Loo Lin School of Medicine.
  • 50 Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.
  • 51 Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
  • 52 Department of Preventive Medicine, College of Medicine, Hanyang University, Seoul, Republic of Korea.
  • 53 Department of Epidemiology, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA.
  • 54 Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
  • 55 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
  • 56 Department of Preventive Medicine & Institute of Wonkwang Medical Science, Wonkwang University College of Medicine, Iksan, Republic of Korea.
  • 57 Department of Ophthalmology, Duke University Medical Center, Durham, NC, USA, Division of Neuroscience, Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
  • 58 Department of Preventive Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
  • 59 Department of Preventive Medicine, School of Medicine, and Health Promotion Research Center, Kyungpook National University, Daegu, Republic of Korea.
  • 60 National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
  • 61 School of Medicine, National Yang-Ming University, Taipei, Taiwan, Section of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
  • 62 Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
  • 63 HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA.
  • 64 NShiley Eye Center, Department of Ophthalmology, University of California at San Diego, La Jolla, CA, USA.
  • 65 Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA, Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
  • 66 Department of Evidence Based Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, and National Center for Cardiovascular Diseases, Beijing, China.
  • 67 Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi, China, Institute of Urology and Nephrology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  • 68 Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan.
  • 69 Saw Swee Hock School of Public Health, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, and National University Health System, Singapore, Singapore Duke-National University of Singapore Graduate Medical School, Singapore, Singapore.
  • 70 Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37203, USA, xiao-ou.shu@vanderbilt.edu.
  • 71 Department of Human Genetics and Disease Diversity, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan, Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, Division of Disease Diversity, Bioresource Research Center, Tokyo Medical and Dental University, Tokyo, Japan.

摘要

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.

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