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

• DOI: 10.1111/j.1469-1809.2009.00560.x
• Publication Date: 2010-01-13T08:32:16Z
• Authors: Todd L. Edwards; William K. Scott; Cherylyn Almonte; Amber Burt; Eric H. Powell; Gary W. Beecham; Liyong Wang; Stephan Züchner; Ioanna Konidari; Gaofeng Wang; Carlos Singer; Fatta Nahab; Burton Scott; Jeffrey M. Stajich; Margaret Pericak‐...; Jonathan Haines; Jeffery M. Vance; Eden R. Martin
• Keywords: 03 medical and health sciences; 0302 clinical medicine; alpha-Synuclein; Humans; Parkinson Disease; tau Proteins; Polymorphism, Single Nucleotide; Genome-Wide Association Study; 3. Good health

SummaryParkinson 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 × 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 × 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.