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

Journal

ANNALS OF HUMAN GENETICS
Volume 74, Issue -, Pages 97-109

Publisher

WILEY
DOI: 10.1111/j.1469-1809.2009.00560.x

Keywords

Parkinson disease; association study; alpha-synuclein; microtubule associated protein tau

Funding

  1. National Institutes of Health [NS39764]
  2. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [P50NS039764] Funding Source: NIH RePORTER
  3. NATIONAL INSTITUTE ON AGING [U24AG021886] Funding Source: NIH RePORTER

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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.

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