We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
- Authors
Hamza, Taye H.; Zabetian, Cyrus P.; Tenesa, Albert; Laederach, Alain; Montimurro, Jennifer; Yearout, Dora; Kay, Denise M.; Doheny, Kimberly F.; Paschall, Justin; Pugh, Elizabeth; Kusel, Victoria I.; Collura, Randall; Roberts, John; Griffith, Alida; Samii, Ali; Scott, William K.; Nutt, John; Factor, Stewart A.; Payami, Haydeh
- Abstract
Parkinson's disease is a common disorder that leads to motor and cognitive disability. We performed a genome-wide association study of 2,000 individuals with Parkinson's disease (cases) and 1,986 unaffected controls from the NeuroGenetics Research Consortium (NGRC). We confirmed associations with SNCA and MAPT, replicated an association with GAK (using data from the NGRC and a previous study, P = 3.2 × 10−9) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 × 10−8), which replicated in two datasets (meta-analysis P = 1.9 × 10−10). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 × 10−10) and late-onset (P = 2.4 × 10−8) disease. The association peak we found was at rs3129882, a noncoding variant in HLA-DRA. Two studies have previously suggested that rs3129882 influences expression of HLA-DR and HLA-DQ. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.
- Subjects
HUMAN genetic variation; HLA histocompatibility antigens; COGNITIVE ability; PARKINSON'S disease; RESEARCH institutes; DATA analysis
- Publication
Nature Genetics, 2010, Vol 42, Issue 9, p781
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.642