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.

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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).

Author information

Author notes

    • Wanqing Wen
    • , Yoon-Shin Cho
    • , Wei Zheng
    • , Rajkumar Dorajoo
    • , Norihiro Kato
    • , Lu Qi
    •  & Chien-Hsiun Chen

    These authors contributed equally to this work.

    • Jer-Yuarn Wu
    • , Jong-Young Lee
    • , Frank B Hu
    • , Toshihiro Tanaka
    • , E Shyong Tai
    •  & Xiao-Ou Shu

    These authors jointly directed this work.


  1. Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Wanqing Wen
    • , Wei Zheng
    • , Ryan J Delahanty
    • , Jirong Long
    • , Qiuyin Cai
    • , Jiajun Shi
    •  & Xiao-Ou Shu
  2. Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Wanqing Wen
    • , Wei Zheng
    • , Ryan J Delahanty
    • , Jirong Long
    • , Qiuyin Cai
    • , Jiajun Shi
    •  & Xiao-Ou Shu
  3. Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Wanqing Wen
    • , Wei Zheng
    • , Ryan J Delahanty
    • , Jirong Long
    • , Qiuyin Cai
    • , Jiajun Shi
    •  & Xiao-Ou Shu
  4. Center for Genome Science, National Institute of Health, Cheongwon-gun, Republic of Korea.

    • Yoon-Shin Cho
    • , Min-Jin Go
    • , Bok-Ghee Han
    •  & Jong-Young Lee
  5. Department of Biomedical Science, Hallym University, Chuncheon, Republic of Korea.

    • Yoon-Shin Cho
  6. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.

    • Rajkumar Dorajoo
    • , Rick T H Ong
    • , Jian-Jun Liu
    •  & Mark Seielstad
  7. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.

    • Rajkumar Dorajoo
  8. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.

    • Norihiro Kato
    •  & Fumihiko Takeuchi
  9. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.

    • Lu Qi
    •  & Frank B Hu
  10. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.

    • Chien-Hsiun Chen
    • , Li-Ching Chang
    • , Mei-Hsin Su
    • , Cathy S J Fann
    •  & Jer-Yuarn Wu
  11. School of Chinese Medicine, China Medical University, Taichung, Taiwan.

    • Chien-Hsiun Chen
    • , Fuu-Jen Tsai
    •  & Jer-Yuarn Wu
  12. Laboratory for Statistical Analysis, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan.

    • Yukinori Okada
    •  & Naoyuki Kamatani
  13. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

    • Yukinori Okada
  14. Department of Basic Medical Research and Education, Ehime University Graduate School of Medicine, Toon, Japan.

    • Yasuharu Tabara
  15. Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

    • Dongfeng Gu
  16. State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Dingliang Zhu
    •  & Yi Zhang
  17. Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Dingliang Zhu
    •  & Yi Zhang
  18. Sino-French Research Center for Life Science and Genomics, Shanghai, China.

    • Dingliang Zhu
    •  & Yi Zhang
  19. Shanghai Key Laboratory of Vascular Biology, Shanghai, China.

    • Dingliang Zhu
  20. Department of Preventive Medicine, University of Southern California Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.

    • Christopher A Haiman
    • , Brian E Henderson
    •  & Gary K Chen
  21. Institute of Urology and Nephrology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.

    • Zengnan Mo
  22. Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.

    • Yu-Tang Gao
    •  & Yong-Bing Xiang
  23. Saw Swee Hock School of Public Health, National University of Singapore, Singapore.

    • Seang-Mei Saw
    • , Daniel P-K Ng
    •  & E Shyong Tai
  24. Department of Preventive Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan.

    • Yoshihiro Kokubo
  25. Department of Endocrinology, The Central Hospital of Xuzhou, Affiliated Hospital of Southeast University, Xuzhou, China.

    • Jun Liang
  26. Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.

    • Mei Hao
    •  & Jiang He
  27. Epidemiology Program, Cancer Research Center, University of Hawaii, Honolulu, Hawaii, USA.

    • Loïc Le Marchand
  28. Medical Scientific Research Center, Guangxi Medical University, Nanning, China.

    • Yanling Hu
  29. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.

    • Tien-Yin Wong
    •  & Tin Aung
  30. Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • Tien-Yin Wong
    •  & Tin Aung
  31. Center for Eye Research Australia, The University of Melbourne, East Melbourne, Victoria, Australia.

    • Tien-Yin Wong
  32. Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan.

    • Michiaki Kubo
  33. Division of Genome Analysis, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.

    • Ken Yamamoto
  34. Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Japan.

    • Tetsuro Miki
  35. State Key Laboratory of Medical Genomics, Molecular Medical Center, Shanghai Institute of Endocrinology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

    • Huaidong Song
  36. Center for Metabolic Disease and Diabetes, First Affiliated Hospital of Guangxi Medical University, Nanning, China.

    • Aihua Tan
  37. Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan.

    • Tatsuhiko Tsunoda
  38. Department of Genomic Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.

    • Naoharu Iwai
  39. Center for Cancer Genomics, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.

    • Jianfeng Xu
  40. Centre for Molecular Epidemiology, National University of Singapore, Singapore.

    • Xueling Sim
  41. Laboratory for Endocrinology and Metabolism, CGM, RIKEN, Yokohama, Japan.

    • Shiro Maeda
  42. National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.

    • Rick T H Ong
  43. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

    • Chun Li
  44. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

    • Yusuke Nakamura
  45. Shanghai Municipal Center for Disease Control and Prevention, Shanghai, China.

    • Wei Lu
  46. Department of Genome Science, Aichi-Gakuin University, School of Dentistry, Nagoya, Japan.

    • Mitsuhiro Yokota
  47. Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.

    • Mark Seielstad
  48. Department of Epidemiology, Harvard University School of Public Health, Boston, Massachusetts, USA.

    • Frank B Hu
  49. Laboratory for Cardiovascular Diseases, CGM, RIKEN, Yokohama, Japan.

    • Toshihiro Tanaka
  50. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

    • E Shyong Tai
  51. Duke–National University of Singapore Graduate Medical School, Singapore.

    • E Shyong Tai


  1. The Genetic Investigation of ANthropometric Traits (GIANT) Consortium

    A complete list of authors is provided in the Supplementary Note.


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T.A., Y.-S.C., Y.-T.G., D.G., B.-G.H., J.H., F.B.H., N. Kamatani, N. Kato, L.-L.-M., J.-Y.L., W.L., Z.M., Y.N., D.P.-K.N., L.Q., S.-M.S., X.-O.S., E.-S.T., F.-J.T., T. Tanaka, F.J.T., T.-Y.W., J.-Y.W., Y.-B.X., J.X., W.Z. and D.Z. supervised the research. Y.-S.C., D.G., J.H., Y.H., N. Kato, J. Liang, Z.M., Y.N., L.Q., M.S., X.-O.S., H.S., E.S.T., T. Tanaka, T.-Y.W., W.Z. and D.Z. conceived and designed the experiments. J.H., Y.H., M.K., J. Liang, M.S., J.S., M.Y. and Y.Z. performed the experiments. L.-C.C., C.-H.C., G.K.C., R.D., M.-J.G., M.H., Y.H., C.L., J. Long, Y.O., L.Q., M.-H.S., Y.T., A.T., T. Tsunoda and W.W. performed the statistical analyses. The GIANT Consortium, Q.C., L.-C.C., C.-H.C., R.J.D., R.D., M.-J.G., M.H., Y.H., N.I., J. Long, T.M., Y.O., R.T.H.O., L.Q., X.S., M.-H.S. and Y.T. analyzed the data. T.A., Q.C., Y.-T.G., C.A.H., B.E.H., N.I., N. Kato, Y.K., L.L.-M., J. Liang, J.-J.L., W.L., D.P.-K.N., L.Q., S.-M.S., M.S., X.-O.S., H.S., E.S.T., F.-J.T., T.-Y.W., J.-Y.W., Y.-B.X., K.Y., M.Y., C.S.J.F. and W.Z. contributed reagents, materials and/or analysis tools. R.J.D., Y.O., X.-O.S., E.S.T., T. Tanaka, W.W. and W.Z. wrote the manuscript. S.M. reviewed the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Xiao-Ou Shu.

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