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

被引:367
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
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
收藏
页码:97 / 109
页数:13
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