Genome-Wide Association Study Confirms SNPs in SNCA and the MAPT Region as Common Risk Factors for Parkinson Disease

被引：369

作者：

Edwards, Todd L. ^{[1
,2
,3
]}

Scott, William K. ^{[1
,2
]}

Almonte, Cherylyn ^{[1
,2
]}

Burt, Amber ^{[1
,2
]}

Powell, Eric H. ^{[1
,2
]}

Beecham, Gary W. ^{[1
,2
]}

Wang, Liyong ^{[1
,2
]}

Zuchner, Stephan ^{[1
,2
]}

Konidari, Ioanna ^{[1
,2
]}

Wang, Gaofeng ^{[1
,2
]}

Singer, Carlos ^{[5
]}

Nahab, Fatta ^{[5
]}

Scott, Burton ^{[6
]}

Stajich, Jeffrey M. ^{[6
]}

Pericak-Vance, Margaret ^{[1
,2
]}

Haines, Jonathan ^{[4
]}

Vance, Jeffery M. ^{[1
,2
]}

Martin, Eden R. ^{[1
,2
]}

机构：

[1] Univ Miami, John P Hussman Inst Human Genom, Miami, FL 33136 USA

[2] Univ Miami, John T Macdonald Fdn Dept Human Genet, Miller Sch Med, Miami, FL 33136 USA

[3] Vanderbilt Univ, Sch Med, Div Epidemiol, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN USA

[4] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN USA

[5] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA

[6] Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA

来源：

ANNALS OF HUMAN GENETICS | 2010年 / 74卷

基金：

美国国家卫生研究院;

关键词：

Parkinson disease; association study; alpha-synuclein; microtubule associated protein tau; MITOCHONDRIAL-DNA POLYMORPHISMS; PROGRESSIVE SUPRANUCLEAR PALSY; ALPHA-SYNUCLEIN; TAU-GENE; NEUROPATHOLOGIC CRITERIA; LINKAGE DISEQUILIBRIUM; PROTEIN-TAU; HAPLOTYPE; MUTATIONS; SUSCEPTIBILITY;

D O I：

10.1111/j.1469-1809.2009.00560.x

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

P>Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 x 10-8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 x 10-8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genome-wide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.

引用

页码：97 / 109

页数：13

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