Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease : Nature Genetics : Nature Publishing Group

Nature Genetics | Letter

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease
Taye H Hamza,Cyrus P Zabetian,Albert Tenesa,Alain Laederach,Jennifer Montimurro,Dora Yearout,Denise M Kay,Kimberly F Doheny,Justin Paschall,Elizabeth Pugh,Victoria I Kusel,Randall Collura,John Roberts,Alida Griffith,Ali Samii,William K Scott,John Nutt,Stewart A Factor& Haydeh Payamihpayami@wadsworth.org

AffiliationsContributionsCorresponding author Journal name:
Nature Genetics
Volume: 42 ,
Pages: 781–785
Year published: (2010)
DOI: doi:10.1038/ng.642
Received09 March 2010
Accepted15 July 2010
Published online15 August 2010

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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leftFigure 1: Genome-wide association P values.

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Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease : Nature Genetics : Nature Publishing Group


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