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Structural equation models (SEM) and polygenic risk score (PRS) analyses are applied to three Swedish twin cohorts (<jats:italic>n<\/jats:italic>\u2009=\u200946,582) and reveal a modest genetic correlation between GERD and asthma of 0.18 and bidirectional PRS and phenotypic associations ranging between OR 1.09-1.14 and no correlations for eczema and allergic rhinitis. Linkage disequilibrium score regression is applied to summary statistics of recently published GERD and asthma\/allergic disease genome wide association studies and reveals a genetic correlation of 0.48 for asthma and GERD, and Genomic SEM supports a single latent factor. A gene-\/gene-set analysis using MAGMA reveals six pleiotropic genes (two at 12q13.2) associated with asthma and GERD. This study provides evidence that there is a common genetic architecture unique to asthma and GERD that may explain comorbidity and requires further investigation.<\/jats:p>","DOI":"10.1038\/s42003-024-06795-1","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T20:21:38Z","timestamp":1725308498000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Shared genetic architecture between gastro-esophageal reflux disease, asthma, and allergic diseases"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6887-9432","authenticated-orcid":false,"given":"Tong","family":"Gong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3765-2067","authenticated-orcid":false,"given":"Ralf","family":"Kuja-Halkola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvid","family":"Harder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Lundholm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-6615","authenticated-orcid":false,"given":"Awad I.","family":"Smew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelli","family":"Lehto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0203-7977","authenticated-orcid":false,"given":"Anna","family":"Andreasson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-3654","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2537-3092","authenticated-orcid":false,"given":"Nicholas J.","family":"Talley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00eblle A.","family":"Pasman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1045-1898","authenticated-orcid":false,"given":"Catarina","family":"Almqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9885-8261","authenticated-orcid":false,"given":"Bronwyn K.","family":"Brew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"6795_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-12-204","volume":"12","author":"T To","year":"2012","unstructured":"To, T. et al. 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NJTs involvement is all outside the submitted work: Norgine (2021)(IBS interest group), personal fees from Allakos (gastroduodenal eosinophilic disease) (2021), twoXAR Viscera Labs, (USA 2021) (IBS-diarrhea), IsoThrive (2021) (esophageal microbiome), BluMaiden (microbiome advisory board) (2021), Rose Pharma (IBS) (2021), Intrinsic Medicine (2022) (human milk oligosaccharide), Comvita M\u0101nuka Honey (2021) (digestive health), Astra Zeneca (2022). In addition, Dr. Talley has a patent Nepean Dyspepsia Index (NDI) 1998, a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo\/Talley, \u201cDiagnostic marker for functional gastrointestinal disorders\u201d Australian Provisional Patent Application 2021901692, \u201dMethods and compositions for treating age-related neurodegenerative disease associated with dysbiosis\u201d US Application No. 63\/537,725.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1077"}}