Genome-wide association study confirms extant PD risk loci among the Dutch

Eur J Hum Genet. 2011 Jun;19(6):655-61. doi: 10.1038/ejhg.2010.254. Epub 2011 Jan 19.

Abstract

In view of the population-specific heterogeneity in reported genetic risk factors for Parkinson's disease (PD), we conducted a genome-wide association study (GWAS) in a large sample of PD cases and controls from the Netherlands. After quality control (QC), a total of 514,799 SNPs genotyped in 772 PD cases and 2024 controls were included in our analyses. Direct replication of SNPs within SNCA and BST1 confirmed these two genes to be associated with PD in the Netherlands (SNCA, rs2736990: P = 1.63 × 10(-5), OR = 1.325 and BST1, rs12502586: P = 1.63 × 10(-3), OR = 1.337). Within SNCA, two independent signals in two different linkage disequilibrium (LD) blocks in the 3' and 5' ends of the gene were detected. Besides, post-hoc analysis confirmed GAK/DGKQ, HLA and MAPT as PD risk loci among the Dutch (GAK/DGKQ, rs2242235: P = 1.22 × 10(-4), OR = 1.51; HLA, rs4248166: P = 4.39 × 10(-5), OR = 1.36; and MAPT, rs3785880: P = 1.9 × 10(-3), OR = 1.19).

Publication types

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

MeSH terms

  • ADP-ribosyl Cyclase / biosynthesis
  • ADP-ribosyl Cyclase / genetics*
  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics*
  • Case-Control Studies
  • DNA Fingerprinting
  • Female
  • GPI-Linked Proteins / biosynthesis
  • GPI-Linked Proteins / genetics
  • Gene Frequency
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Middle Aged
  • Netherlands
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Protein-Serine-Threonine Kinases / biosynthesis
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk Factors
  • alpha-Synuclein / biosynthesis
  • alpha-Synuclein / genetics*
  • tau Proteins / biosynthesis
  • tau Proteins / genetics*

Substances

  • Antigens, CD
  • GPI-Linked Proteins
  • Intracellular Signaling Peptides and Proteins
  • MAPT protein, human
  • SNCA protein, human
  • alpha-Synuclein
  • tau Proteins
  • GAK protein, human
  • Protein-Serine-Threonine Kinases
  • ADP-ribosyl Cyclase
  • ADP-ribosyl cyclase 2