Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease (original) (raw)

Nature Genetics volume 41, pages 1303–1307 (2009)Cite this article

Abstract

To identify susceptibility variants for Parkinson's disease (PD), we performed a genome-wide association study (GWAS) and two replication studies in a total of 2,011 cases and 18,381 controls from Japan. We identified a new susceptibility locus on 1q32 (P = 1.52 × 10−12) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 × 10−9). We also detected strong associations at SNCA on 4q22 (P = 7.35 × 10−17) and LRRK2 on 12q12 (P = 2.72 × 10−8), both of which are implicated in autosomal dominant forms of parkinsonism. By comparing results of a GWAS performed on individuals of European ancestry, we identified PARK16, SNCA and LRRK2 as shared risk loci for PD and BST1 and MAPT as loci showing population differences. Our results identify two new PD susceptibility loci, show involvement of autosomal dominant parkinsonism loci in typical PD and suggest that population differences contribute to genetic heterogeneity in PD.

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Acknowledgements

We are grateful to the individuals with PD who participated in this study. We also thank T. Takeshima and E. Ohta for PD samples, H. Inoko and K. Tokunaga for control samples, M. Kanagawa and K. Ura for editing, K. Yasuno and R. Ashida for analyses, and K. Yamada for genotyping. We appreciate all the volunteers and participating institutions of BioBank Japan for samples. This work was supported by a grant from Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST); by the Global COE program and KAKENHI (17019044 and 19590990), both from the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by the Grant-in-Aid for 'the Research Committee for the Neurodegenerative Diseases' of the Research on Measures for Intractable Diseases and Research Grant (H19-Genome-Ippan-001), all from the Ministry of Health, Labor and Welfare of Japan.

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Authors and Affiliations

  1. Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan
    Wataru Satake, Yuko Nakabayashi, Ikuko Mizuta, Yushi Hirota, Chiyomi Ito & Tatsushi Toda
  2. Division of Clinical Genetics, Osaka University Graduate School of Medicine, Suita, Japan
    Wataru Satake, Yuko Nakabayashi, Ikuko Mizuta, Yushi Hirota, Chiyomi Ito & Tatsushi Toda
  3. Department of Neurology, Osaka University Graduate School of Medicine, Suita, Japan
    Wataru Satake & Saburo Sakoda
  4. Center for Genomic Medicine, RIKEN, Yokohama, Japan
    Michiaki Kubo, Takahisa Kawaguchi, Tatsuhiko Tsunoda & Yusuke Nakamura
  5. Department of Neurology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
    Masahiko Watanabe
  6. Division of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
    Atsushi Takeda
  7. Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan
    Hiroyuki Tomiyama & Nobutaka Hattori
  8. Department of Neurology, Tottori University Faculty of Medicine, Yonago, Japan
    Kenji Nakashima
  9. Department of Neurology, Sagamihara National Hospital, Sagamihara, Japan
    Kazuko Hasegawa
  10. Division of Clinical Immunology, Graduate School of Medical Sciences, Kitasato University, Sagamihara, Japan
    Fumiya Obata
  11. RIKEN Brain Science Institute, Saitama, Japan
    Takeo Yoshikawa
  12. Department of Epidemiology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
    Hideshi Kawakami
  13. Department of Neurology, Kagawa Prefectural Central Hospital, Takamatsu, Japan
    Mitsutoshi Yamamoto
  14. Department of Neurology, National Center Hospital of Neurology and Psychiatry, Kodaira, Japan
    Miho Murata
  15. Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Yusuke Nakamura

Authors

  1. Wataru Satake
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  2. Yuko Nakabayashi
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  3. Ikuko Mizuta
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  4. Yushi Hirota
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  5. Chiyomi Ito
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  6. Michiaki Kubo
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  7. Takahisa Kawaguchi
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  8. Tatsuhiko Tsunoda
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  9. Masahiko Watanabe
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  10. Atsushi Takeda
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  11. Hiroyuki Tomiyama
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  12. Kenji Nakashima
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  13. Kazuko Hasegawa
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  14. Fumiya Obata
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  15. Takeo Yoshikawa
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  16. Hideshi Kawakami
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  17. Saburo Sakoda
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  18. Mitsutoshi Yamamoto
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  19. Nobutaka Hattori
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  20. Miho Murata
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  21. Yusuke Nakamura
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  22. Tatsushi Toda
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Contributions

T. Toda conceived the study. W.S., I.M. and T. Toda designed the study. W.S., Y.N., C.I., M.K. and T.Y. performed genotyping. W.S. and T. Toda wrote the manuscript. W.S., T.K. and T. Tsunoda performed data analysis. W.S., I.M., Y.H., M.W., A.T., H.T., K.N., K.H., F.O., H.K., S.S., M.Y., N.H., M.M. and T. Toda managed Parkinson clinical information and DNA samples. M.K. and Y.N. managed DNA samples belonging to BioBank Japan. T. Toda obtained funding for the study.

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Correspondence toTatsushi Toda.

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Satake, W., Nakabayashi, Y., Mizuta, I. et al. Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease.Nat Genet 41, 1303–1307 (2009). https://doi.org/10.1038/ng.485

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