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

Wataru Satake, Yuko Nakabayashi, Ikuko Mizuta, Yushi Hirota, Chiyomi Ito, Michiaki Kubo, Takahisa Kawaguchi, Tatsuhiko Tsunoda, Masahiko Watanabe, Atsushi Takeda, Hiroyuki Tomiyama, Kenji Nakashima, Kazuko Hasegawa, Fumiya Obata, Takeo Yoshikawa, Hideshi Kawakami, Saburo Sakoda, Mitsutoshi Yamamoto, Nobutaka Hattori, Miho MurataYusuke Nakamura, Tatsushi Toda

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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.

Original languageEnglish
Pages (from-to)1303-1307
Number of pages5
JournalNature Genetics
Volume41
Issue number12
DOIs
Publication statusPublished - 2009 Dec

ASJC Scopus subject areas

  • Genetics

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    Satake, W., Nakabayashi, Y., Mizuta, I., Hirota, Y., Ito, C., Kubo, M., Kawaguchi, T., Tsunoda, T., Watanabe, M., Takeda, A., Tomiyama, H., Nakashima, K., Hasegawa, K., Obata, F., Yoshikawa, T., Kawakami, H., Sakoda, S., Yamamoto, M., Hattori, N., ... Toda, T. (2009). Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease. Nature Genetics, 41(12), 1303-1307. https://doi.org/10.1038/ng.485