Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases

摘要: Importance Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an between immune-mediated diseases Parkinson disease (PD). The post-GWAS era provides opportunity for cross-phenotype different complex phenotypes. Objectives To test the hypothesis that there are common genetic risk variants conveying both PD autoimmune (ie, pleiotropy) to identify new shared their pathways by applying a novel statistical framework in approach. Design, Setting, Participants Using conjunction false discovery rate method, this study analyzed GWAS data from selection archetypal among 138 511 individuals European ancestry systemically investigated pleiotropy type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac psoriasis, multiple sclerosis. NeuroX (6927 cases 6108 controls) were used replication. biological correlation top loci through protein-protein interaction changes gene expression methylation levels. dates analysis June 10, 2015, March 4, 2017. Main Outcomes Measures primary outcome was list involved diseases. Results Genome-wide conjunctional identified 17 at less than 0.05 with overlap diseases, including known adjacent GAK , HLA-DRB5 LRRK2 MAPT colitis disease. Replication confirmed involvement HLA TRIM10 SE TD1A PD. Among genes discovered, WNT3 KANSL1 CRHR1 BOLA2 GUCY1A3 within network genes. A subset significantly associated or levels Conclusions Relevance findings provide mechanistic insights into these results may have implications future therapeutic trials involving anti-inflammatory agents.