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Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations

Nature Genetics volume 44, pages 302–306 (2012)Cite this article

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Abstract

Obesity is a disorder with a complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index, the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here we report a genome-wide association study and replication studies with 62,245 east Asian subjects, which identified two new body mass index–associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 × 10−11) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 × 10−9), as well as several previously reported loci (the SEC16B, BDNF, FTO, MC4R and GIPR loci, P < 5.0 × 10−8). We subsequently performed gene-gene interaction analyses and identified an interaction (P = 2.0 × 10−8) between a SNP in the KLF9 locus (rs11142387) and one in the MSTN (also known as GDF8) locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.

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Figure 1: Results of the GWAS for BMI.
Figure 2: Gene-gene interactions between the KLF9 and MSTN loci.

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Acknowledgements

We thank K. Tobe and M. Iwata at the First Department of Internal Medicine, Faculty of Medicine, Toyama University, H. Hirose at Health Center, Keio University School of Medicine and all the staff of the Laboratory for Endocrinology, Metabolism and Statistical Analysis at CGM, RIKEN for their assistance. This study was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Laboratory for Statistical Analysis, Center for Genomic Medicine (CGM), RIKEN, Yokohama, Japan

    Yukinori Okada, Hiroko Ohmiya, Atsushi Takahashi, Natsuhiko Kumasaka & Naoyuki Kamatani

  2. Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan

    Yukinori Okada & Kazuhiko Yamamoto

  3. Laboratory for Genotyping Development, CGM, RIKEN, Yokohama, Japan

    Michiaki Kubo & Naoya Hosono

  4. Laboratory for Endocrinology and Metabolism, CGM, RIKEN, Yokohama, Japan

    Shiro Maeda

  5. Department of Medicine, Division of Epidemiology, Vanderbilt Center of Epidemiology and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA

    Wanqing Wen & Wei Zheng

  6. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore

    Rajkumar Dorajoo

  7. Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK

    Rajkumar Dorajoo

  8. Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Korea

    Min Jin Go

  9. Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan

    Norihiro Kato

  10. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan

    Jer-Yuarn Wu

  11. School of Chinese Medicine, China Medical University, Taichung, Taiwan

    Jer-Yuarn Wu

  12. Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA

    Qi Lu

  13. Laboratory for Medical Informatics, CGM, RIKEN, Yokohama, Japan

    Tatsuhiko Tsunoda

  14. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

    Yusuke Nakamura

  15. Laboratory for Cardiovascular Diseases, CGM, RIKEN, Yokohama, Japan

    Toshihiro Tanaka

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  1. Yukinori Okada
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Consortia

GIANT consortium

Contributions

Y.O. and T. Tanaka designed the study and drafted the manuscript. N.H. and M.K. performed the genotyping. Y.O., H.O., A.T., N. Kumasaka and T. Tsunoda performed the statistical analyses. Y.O. and M.K. managed the clinical information. W.W., R.D., M.J.G., W.Z., N. Kato, J.-Y.W. and Q.L. managed replication study set 3. The GIANT consortium managed the association study in Europeans. S.M., K.Y., Y.N., N. Kamatani and T. Tanaka supervised the study.

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Correspondence to Yukinori Okada.

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The authors declare no competing financial interests.

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A full list of members is provided in the Supplementary Note.

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Supplementary Tables 1–6, Supplementary Figures 1–5 and Supplementary Note. (PDF 593 kb)

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Okada, Y., Kubo, M., Ohmiya, H. et al. Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. Nat Genet 44, 302–306 (2012). https://doi.org/10.1038/ng.1086

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