{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T23:17:14Z","timestamp":1789082234794,"version":"build-2803163510"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"crossref","award":["2017-02175"],"award-info":[{"award-number":["2017-02175"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"United Kingdom\u2019s Medical Research Council","award":["MC_UU_00019\/2"],"award-info":[{"award-number":["MC_UU_00019\/2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,12,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Parkinson\u2019s disease and inflammatory bowel disease have been increasingly associated, implying shared pathophysiology. To explore biological explanations for the reported connection, we leveraged summary statistics of updated genome-wide association studies and characterized the genetic overlap between the two diseases. Aggregated genetic association data were available for 37 688 cases versus 981 372 controls for Parkinson\u2019s disease and 25 042 cases versus 34 915 controls for inflammatory bowel disease. Genetic correlation was estimated with the high-definition likelihood method. Genetic variants with joint association to both diseases were identified by conditional false discovery rate framework and further annotated to reveal shared loci, genes, and enriched pathways. For both Crohn\u2019s disease and ulcerative colitis, the two main subtypes of inflammatory bowel disease, we detected weak but statistically significant genetic correlations with Parkinson\u2019s disease (Crohn\u2019s disease: rg = 0.06, P = 0.01; ulcerative colitis: rg = 0.06, P = 0.03). A total of 1290 variants in 27 independent genomic loci were detected to associate with Parkinson\u2019s disease and Crohn\u2019s disease at conjunctional false discovery rate under 0.01 and 1359 variants in 15 loci were pleiotropic to Parkinson\u2019s disease and ulcerative colitis. Among the identified pleiotropic loci, 23 are novel and have never been associated with both phenotypes. A mixture of loci conferring either same or opposing genetic effects on two phenotypes was also observed. Positional and expression quantitative trait loci mapping prioritized 296 and 253 genes for Parkinson\u2019s disease with Crohn\u2019s disease and ulcerative colitis, respectively, among which only &amp;lt;10% are differentially expressed in both colon and substantia nigra. These genes were identified to overrepresent in pathways regulating gene expression and post-translational modification beyond several immune-related pathways enriched by major histocompatibility complex genes. In conclusion, we found robust evidence for a genetic link between Parkinson\u2019s disease and inflammatory bowel disease. The identified genetic overlap is complex at the locus and gene levels, indicating the presence of both synergistic and antagonistic pleiotropy. At the functional level, our findings implied a role of immune-centered mechanisms in the reported gut-brain connection.<\/jats:p>","DOI":"10.1093\/braincomms\/fcad002","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T22:00:03Z","timestamp":1672696803000},"source":"Crossref","is-referenced-by-count":27,"title":["Genetic overlap between Parkinson\u2019s disease and inflammatory bowel disease"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1999-9304","authenticated-orcid":false,"given":"Xiaoying","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-8326","authenticated-orcid":false,"given":"Alexander","family":"Ploner","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas F","family":"Ludvigsson","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"},{"name":"Department of Pediatrics, \u00d6rebro University Hospital , SE-70116 \u00d6rebro , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan M","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"},{"name":"MRC Unit for Lifelong Health and Ageing at UCL, University College London , London WC1E 7HE , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Wirdefeldt","sequence":"additional","affiliation":[{"name":"Department of Medical Epidemiology and Biostatistics, Karolinska Institutet , SE-17165 Stockholm , Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet , SE-17177 Stockholm , Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"issue":"11","key":"2023011816245283500_fcad002-B1","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/nrneurol.2015.197","article-title":"Pathogenesis of Parkinson disease\u2014The gut\u2013brain axis and environmental 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