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

被引：1017

作者：

Satake, Wataru ^{[1
,2
,3
]}

Nakabayashi, Yuko ^{[1
,2
]}

Mizuta, Ikuko ^{[1
,2
]}

Hirota, Yushi ^{[1
,2
]}

Ito, Chiyomi ^{[1
,2
]}

Kubo, Michiaki ^{[4
]}

Kawaguchi, Takahisa ^{[4
]}

Tsunoda, Tatsuhiko ^{[4
]}

Watanabe, Masahiko ^{[5
]}

Takeda, Atsushi ^{[6
]}

Tomiyama, Hiroyuki ^{[7
]}

Nakashima, Kenji ^{[8
]}

Hasegawa, Kazuko ^{[9
]}

Obata, Fumiya ^{[10
]}

Yoshikawa, Takeo ^{[11
]}

Kawakami, Hideshi ^{[12
]}

Sakoda, Saburo ^{[3
]}

Yamamoto, Mitsutoshi ^{[13
]}

Hattori, Nobutaka ^{[7
]}

Murata, Miho ^{[14
]}

Nakamura, Yusuke ^{[4
,15
]}

Toda, Tatsushi ^{[1
,2
]}

机构：

[1] Kobe Univ, Grad Sch Med, Div Neurol Mol Brain Sci, Kobe, Hyogo 657, Japan

[2] Osaka Univ, Grad Sch Med, Div Clin Genet, Suita, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka, Japan

[4] RIKEN, Ctr Genom Med, Yokohama, Kanagawa, Japan

[5] Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Neurol, Tsukuba, Ibaraki, Japan

[6] Tohoku Univ, Grad Sch Med, Div Neurol, Sendai, Miyagi 980, Japan

[7] Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan

[8] Tottori Univ, Fac Med, Dept Neurol, Yonago, Tottori 683, Japan

[9] Sagamihara Natl Hosp, Dept Neurol, Sagamihara, Kanagawa, Japan

[10] Kitasato Univ, Grad Sch Med Sci, Div Clin Immunol, Sagamihara, Kanagawa 228, Japan

[11] RIKEN, Brain Sci Inst, Saitama, Japan

[12] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Epidemiol, Hiroshima, Japan

[13] Kagawa Prefectural Cent Hosp, Dept Neurol, Takamatsu, Kagawa, Japan

[14] Natl Ctr Hosp Neurol & Psychiat, Dept Neurol, Kodaira, Tokyo, Japan

[15] Univ Tokyo, Inst Ind Sci, Ctr Human Genome, Tokyo, Japan

来源：

NATURE GENETICS | 2009年 / 41卷 / 12期

基金：

日本科学技术振兴机构;

关键词：

PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN; TAU GENE; MUTATIONS; LRRK2; SUSCEPTIBILITY; CLONING; DEMENTIA; CALCIUM;

D O I：

10.1038/ng.485

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-12)) and designated this as PARK16, and we also identified BST1 on 4p15 as a second new risk locus (P = 3.94 x 10(-9)). We also detected strong associations at SNCA on 4q22 (P = 7.35 x 10(-17)) and LRRK2 on 12q12 (P = 2.72 x 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.

引用

页码：1303 / U61

页数：6

共 42 条

[41] Crystallographic studies on human BST-1/CD157 with ADP-ribosyl cyclase and NAD glycohydrolase activities [J].

Yamamoto-Katayama, S ;

Ariyoshi, M ;

Ishihara, K ;

Hirano, T ;

Jingami, H ;

Morikawa, K .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 316 (03) :711-723

[42] Mutations in LRRK2 cause autosomal-dominant Parkinsonism with pleomorphic pathology [J].

Zimprich, A ;

Biskup, S ;

Leitner, P ;

Lichtner, P ;

Farrer, M ;

Lincoln, S ;

Kachergus, J ;

Hulihan, M ;

Uitti, RJ ;

Calne, DB ;

Stoessl, AJ ;

Pfeiffer, RF ;

Patenge, N ;

Carbajal, IC ;

Vieregge, P ;

Asmus, F ;

Müller-Myhsok, B ;

Dickson, DW ;

Meitinger, T ;

Strom, TM ;

Wszolek, ZK ;

Gasser, T .

NEURON, 2004, 44 (04) :601-607

← 1 2 3 4 5 →