DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Parkinson's disease. The EFO term Parkinson's disease was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: Parkinson's disease

SCORE TYPE:

P-Value

THRESHOLD:

<= 0.05

GENES IN THRESHOLD:

5

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-10-22

SPECIES:

AUTHORS:

TH Hamza, CP Zabetian, A Tenesa, A Laederach, J Montimurro, D Yearout, DM Kay, KF Doheny, J Paschall, E Pugh, VI Kusel, R Collura, J Roberts, A Griffith, A Samii, WK Scott, J Nutt, SA Factor, H Payami

TITLE:

Common genetic variation in the HLA region is associated with late-onset sporadic Parkinson's disease.

JOURNAL:

Nature genetics Sep 2010, Vol 42, pp. 781-5

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. PUBMED: 20711177
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