title: Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.
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 x 10(-9)) and detected a new association with the HLA region (using data from the NGRC only, P = 2.9 x 10(-8)), which replicated in two datasets (meta-analysis P = 1.9 x 10(-10)). The HLA association was uniform across all genetic and environmental risk strata and was strong in sporadic (P = 5.5 x 10(-10)) and late-onset (P = 2.4 x 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.
authors: New York State Department of Health Wadsworth Center, Albany, New York, USA.
authors: Taye H
authors: TH
authors: Hamza
authors: Cyrus P
authors: CP
authors: Zabetian
authors: Albert
authors: A
authors: Tenesa
authors: Alain
authors: A
authors: Laederach
authors: Jennifer
authors: J
authors: Montimurro
authors: Dora
authors: D
authors: Yearout
authors: Denise M
authors: DM
authors: Kay
authors: Kimberly F
authors: KF
authors: Doheny
authors: Justin
authors: J
authors: Paschall
authors: Elizabeth
authors: E
authors: Pugh
authors: Victoria I
authors: VI
authors: Kusel
authors: Randall
authors: R
authors: Collura
authors: John
authors: J
authors: Roberts
authors: Alida
authors: A
authors: Griffith
authors: Ali
authors: A
authors: Samii
authors: William K
authors: WK
authors: Scott
authors: John
authors: J
authors: Nutt
authors: Stewart A
authors: SA
authors: Factor
authors: Haydeh
authors: H
authors: Payami
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000502:physiology; D055106:Genome-Wide Association Study; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D016017:Odds Ratio; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics*; D055815:Young Adult
chemical_list: D006680:HLA Antigens