西亞試劑：Common genetic variation in the HLA region is associated wi

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease
Taye H Hamza1, Cyrus P Zabetian2,3, Albert Tenesa4, Alain Laederach1, Jennifer Montimurro1, Dora Yearout1,2,3, Denise M Kay1, Kimberly F Doheny5, Justin Paschall6, Elizabeth Pugh5, Victoria I Kusel1, Randall Collura1, John Roberts7, Alida Griffith8, Ali Samii2,3, William K Scott9, John Nutt10, Stewart A Factor11 & Haydeh Payami1

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)1, 2, 3, 4, 5. We confirmed associations with SNCA2, 6, 7, 8 and MAPT3, 7, 8, 9, replicated an association with GAK9 (using data from the NGRC and a previous study9, 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-DQ10, 11. The brains of individuals with Parkinson's disease show upregulation of DR antigens and the presence of DR-positive reactive microglia12, and nonsteroidal anti-inflammatory drugs reduce Parkinson's disease risk4, 13. The genetic association with HLA supports the involvement of the immune system in Parkinson's disease and offers new targets for drug development.

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