TY - JOUR
T1 - Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease
AU - Satake, Wataru
AU - Nakabayashi, Yuko
AU - Mizuta, Ikuko
AU - Hirota, Yushi
AU - Ito, Chiyomi
AU - Kubo, Michiaki
AU - Kawaguchi, Takahisa
AU - Tsunoda, Tatsuhiko
AU - Watanabe, Masahiko
AU - Takeda, Atsushi
AU - Tomiyama, Hiroyuki
AU - Nakashima, Kenji
AU - Hasegawa, Kazuko
AU - Obata, Fumiya
AU - Yoshikawa, Takeo
AU - Kawakami, Hideshi
AU - Sakoda, Saburo
AU - Yamamoto, Mitsutoshi
AU - Hattori, Nobutaka
AU - Murata, Miho
AU - Nakamura, Yusuke
AU - Toda, Tatsushi
N1 - Funding Information:
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 GrantinAid for ‘the Research Committee for the Neurodegenerative Diseases’ of the Research on Measures for Intractable Diseases and Research Grant (H19GenomeIppan001), all from the Ministry of Health, Labor and Welfare of Japan.
PY - 2009/12
Y1 - 2009/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=70549084415&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70549084415&partnerID=8YFLogxK
U2 - 10.1038/ng.485
DO - 10.1038/ng.485
M3 - Article
C2 - 19915576
AN - SCOPUS:70549084415
SN - 1061-4036
VL - 41
SP - 1303
EP - 1307
JO - Nature Genetics
JF - Nature Genetics
IS - 12
ER -