Fine mapping of the HLA locus in Parkinson's disease in Europeans.

ABSTRACT: We fine mapped the leukocyte antigen (HLA) region in 13,770 Parkinson's disease (PD) patients, 20,214 proxy-cases, and 490,861 controls of European origin. Four HLA types were associated with PD after correction for multiple comparisons, HLA-DQA1*03:01, HLA-DQB1*03:02, HLA-DRB1*04:01, and HLA-DRB1*04:04. Haplotype analyses followed by amino acid analysis and conditional analyses suggested that the association is protective and primarily driven by three specific amino acid polymorphisms present in most HLA-DRB1*04 subtypes-11V, 13H, and 33H (OR = 0.87, 95% CI: 0.83-0.90, p < 8.23 × 10^-9 for all three variants). No other effects were present after adjustment for these amino acids. Our results suggest that specific HLA-DRB1 variants are associated with reduced risk of PD, providing

SUBMITTER: Yu E 

PROVIDER: S-EPMC8455634 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature