Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease

Ann Hum Genet. 2010 Mar;74(2):97-109. doi: 10.1111/j.1469-1809.2009.00560.x. Epub 2010 Jan 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Genome-Wide Association Study*
  • Humans
  • Parkinson Disease / genetics*
  • Parkinson Disease / metabolism
  • Polymorphism, Single Nucleotide*
  • alpha-Synuclein / genetics*
  • alpha-Synuclein / metabolism
  • tau Proteins / genetics*
  • tau Proteins / metabolism

Substances

  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins