Genome-wide Pleiotropy Between Parkinson Disease and Autoimmune Diseases.
Aree Witoelar,Iris E. Jansen,Yunpeng Wang,Rahul S. Desikan,J. Raphael Gibbs,Cornelis Blauwendraat,Wesley K. Thompson,Dena G. Hernandez,Srdjan Djurovic,Andrew J. Schork,Francesco Bettella,David Ellinghaus,Andre Franke,Benedicte A. Lie,Linda K. McEvoy,Tom H. Karlsen,Suzanne Lesage,Huw R. Morris,Alexis Brice,Nicholas W. Wood,Peter Heutink,John Hardy,Andrew B. Singleton,Anders M. Dale,Thomas Gasser,Ole A. Andreassen,Manu Sharma +26 more
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TLDR
The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes, which may have implications for future therapeutic trials involving anti-inflammatory agents.Abstract:
Importance Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an association between immune-mediated diseases and Parkinson disease (PD). The post-GWAS era provides an opportunity for cross-phenotype analyses between different complex phenotypes. Objectives To test the hypothesis that there are common genetic risk variants conveying risk of both PD and autoimmune diseases (ie, pleiotropy) and to identify new shared genetic variants and their pathways by applying a novel statistical framework in a genome-wide approach. Design, Setting, and Participants Using the conjunction false discovery rate method, this study analyzed GWAS data from a selection of archetypal autoimmune diseases among 138 511 individuals of European ancestry and systemically investigated pleiotropy between PD and type 1 diabetes, Crohn disease, ulcerative colitis, rheumatoid arthritis, celiac disease, psoriasis, and multiple sclerosis. NeuroX data (6927 PD cases and 6108 controls) were used for replication. The study investigated the biological correlation between the top loci through protein-protein interaction and changes in the gene expression and methylation levels. The dates of the analysis were June 10, 2015, to March 4, 2017. Main Outcomes and Measures The primary outcome was a list of novel loci and their pathways involved in PD and autoimmune diseases. Results Genome-wide conjunctional analysis identified 17 novel loci at false discovery rate less than 0.05 with overlap between PD and autoimmune diseases, including known PD loci adjacent to GAK , HLA-DRB5 , LRRK2 , and MAPT for rheumatoid arthritis, ulcerative colitis and Crohn disease. Replication confirmed the involvement of HLA , LRRK2 , MAPT , TRIM10 , and SE TD1A in PD. Among the novel genes discovered, WNT3 , KANSL1 , CRHR1 , BOLA2 , and GUCY1A3 are within a protein-protein interaction network with known PD genes. A subset of novel loci was significantly associated with changes in methylation or expression levels of adjacent genes. Conclusions and Relevance The study findings provide novel mechanistic insights into PD and autoimmune diseases and identify a common genetic pathway between these phenotypes. The results may have implications for future therapeutic trials involving anti-inflammatory agents.read more
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Association between Microscopic Colitis and Parkinson's Disease in a Swedish Population
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TL;DR: In this article, the authors examined the association of Microscopic colitis (MC) with Parkinson's disease (PD) using Cox regression models and found that MC was associated with an adjusted HR of 1.76 for PD, but the association attenuated substantially during follow-up.
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Etude des mécanismes cellulaires et moléculaires impliqués dans les effets neuroprotecteurs du gliopeptide OctaDecaNeuropeptide (ODN) dans un model murin de la Maladie de Parkinson
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Epidemiological Evidence for an Immune Component of Parkinson’s Disease
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Fire prevention in the Parkinson’s disease brain
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The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis
TL;DR: Parkinson's disease (PD) is a neurodegenerative disorder that frequently occurs in the older population as mentioned in this paper , however, some studies have shown conflicting results regarding the association between PD and AIDs.
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TL;DR: The results identify several novel loci associated with plasma lipids that are also associated with CAD and provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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Mutations in LRRK2 Cause Autosomal-Dominant Parkinsonism with Pleomorphic Pathology
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TL;DR: High-resolution recombination mapping and candidate gene sequencing in 46 families found six disease-segregating mutations in a gene encoding a large, multifunctional protein, LRRK2 (leucine-rich repeat kinase 2), which may be central to the pathogenesis of several major neurodegenerative disorders associated with parkinsonism.
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