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Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits

Nature Genetics volume 43, pages 990–995 (2011)Cite this article

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Abstract

To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.

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Figure 1
Figure 2: Regional plot of new variants that reached genome-wide significance (overall meta P < 5 × 10−8).

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Acknowledgements

This work was supported by grants from Korea Centers for Disease Control and Prevention (4845-301, 4851-302, 4851-307) and an intramural grant from the Korea National Institute of Health (2010-N73002-00), the Republic of Korea. The Shanghai study was supported by grants from National 973 Program (2011CB504001), National Natural Science Foundation of China (30800617), China. BioBank Japan project is supported by the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Author notes

  1. Young Jin Kim, Min Jin Go and Hyung-Lae Kim: These authors contributed equally to this work.

Authors and Affiliations

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

    Young Jin Kim, Min Jin Go, Chang Bum Hong, Yun Kyoung Kim, Ji Young Lee, Joo-Yeon Hwang, Ji Hee Oh, Dong-Joon Kim, Nam Hee Kim, Soeui Kim, Eun Jung Hong, Ji-Hyun Kim, Haesook Min, Yeonjung Kim, Hyung-Lae Kim, Bok-Ghee Han, Jong-Young Lee & Yoon Shin Cho

  2. Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China

    Cheng Hu, Rong Zhang & Weiping Jia

  3. Center for Genomic Medicine, RIKEN, Kanagawa, Japan

    Yukinori Okada, Atsushi Takahashi, Michiaki Kubo, Toshihiro Tanaka & Naoyuki Kamatani

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

    Yukinori Okada

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

    Koichi Matsuda

  6. Department of Statistics, College of Natural Science, Seoul National University, Seoul, Korea

    Taesung Park

  7. Department of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul, Korea

    Bermseok Oh

  8. Merck Research Laboratories, External Scientific Affairs, Merck, Sharp & Dohme Korea, Seoul, Korea

    Kuchan Kimm

  9. Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea

    Daehee Kang

  10. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Korea

    Chol Shin

  11. Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea

    Nam H Cho

  12. Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul, Korea

    Hyung-Lae Kim

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  1. Young Jin Kim
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MAGIC consortium

Contributions

The study was supervised by J.-Y.L., Y.S.C., T.T., N.K., K.M., W.J., K.K., B.O., H.-L.K. and B.-G.H. Genotyping experiments were designed by Y.S.C., B.O., M.K., C.H., H.-L.K. and J.-Y.L. Genotyping experiments were performed by J.H.O., D.-J.K., M.K., C.H. and R.Z. DNA sample preparation was carried out by E.J.H. and J.-H.K. Phenotype information was collected by N.H.K., S.K., H.M., Y.K., N.H.C., C.S. and D.K. Statistical analysis was performed by M.J.G., Y.K., Y.K.K., J.Y.L., S.K., Y.O., A.T., C.H. and T.P. Bioinformatic analysis was conducted by Y.J.K., C.B.H., M.J.G., C.H., J.-Y.H. and Y.S.C. The manuscript was written by Y.J.K., M.J.G., Y.O. and Y.S.C. All authors reviewed the manuscript.

Corresponding author

Correspondence to Yoon Shin Cho.

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The authors declare no competing financial interests.

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A list of members is provided in the Supplementary Note.

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Supplementary Note, Supplementary Tables 1–9 and Supplementary Figures 1–5. (PDF 6368 kb)

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Kim, Y., Go, M., Hu, C. et al. Large-scale genome-wide association studies in east Asians identify new genetic loci influencing metabolic traits. Nat Genet 43, 990–995 (2011). https://doi.org/10.1038/ng.939

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