Association between Parkinson's disease and the HLA-DRB1 locus

Mov Disord. 2012 Aug;27(9):1104-10. doi: 10.1002/mds.25035. Epub 2012 Jul 13.


Two genome-wide association studies (GWASs) recently highlighted the HLA-DRA and HLA-DRB5 genes as associated with Parkinson disease (PD). However, because HLA-DRA displays a low level of polymorphisms and HLA-DRB5 is only present in approximately 20% of the population, these findings are difficult to interpret. Our aims were: (1) to replicate and investigate in greater detail the association between PD and the HLA-DR region; (2) to identify PD-associated HLA alleles; and (3) to perform a meta-analysis of our top finding. As part of 2 French population-based case-control studies of PD including highly ethnically homogeneous participants, we investigated the association between PD and 51 Single-nucleotide polymorphisms (SNPs) in the HLA-DR region. HLA-DRB1 alleles were imputed using the HLA(*) IMP software. HLA typing was performed in a subsample of the participants. We performed a meta-analysis of our top finding based on 4 GWAS data sets. Among 499 cases and 1123 controls, after correction for multiple testing, we found an association with rs660895 (OR/minor allele, 0.70; 95% CI, 0.57-0.87) within the HLA-DRB1 gene, which encodes the most polymorphic HLA-DR chain (DRβ). A meta-analysis (7996 cases, 36455 controls) confirmed this association (OR, 0.86; 95% CI, 0.82-0.91; P < .0001). SNP-based imputation of HLA alleles showed an inverse association between PD and the HLA-DRB1(*) 04 allele. We replicated an association between PD and the HLA-DR region and provided further insight into the loci and alleles involved. The highly polymorphic HLA-DRB1 locus contains rs660895, which represents a more legitimate candidate than previous ones. Our finding is in agreement with the hypothesis of an immune component in PD pathophysiology.

Publication types

  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA / genetics
  • Female
  • France / epidemiology
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • HLA-DRB1 Chains / genetics*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / epidemiology
  • Parkinson Disease / genetics*
  • Polymorphism, Single Nucleotide
  • Socioeconomic Factors


  • HLA-DRB1 Chains
  • DNA