{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T05:29:30Z","timestamp":1734499770498,"version":"3.30.2"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aims to investigate the potential causal relationship, shared genomic loci, as well as potential molecular pathways and tissue\u2010specific expression patterns between gastroesophageal reflux disease (GERD) and the risk of hospitalized\/severe 2019 coronavirus disease (COVID\u201019).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employed linkage disequilibrium score regression and bidirectional Mendelian randomization (MR) analysis to explore potential genetic associations between GERD (<jats:italic>N<\/jats:italic>\u00a0=\u00a0602,604) and hospitalized COVID\u201019 (<jats:italic>N<\/jats:italic>\u00a0=\u00a02095,324) as well as severe COVID\u201019 (<jats:italic>N<\/jats:italic>\u00a0=\u00a01086,211). Additionally, shared genomic loci were extracted from common pivotal regions, further confirmed through corresponding colocalization analyses. GERD\u2010driven molecular pathway network was constructed using extensive literature data mining to understand the molecular\u2010level impacts of GERD on COVID\u201019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed a significant positive genetic correlation between GERD and both hospitalized (<jats:italic>r<jats:sub>g<\/jats:sub><\/jats:italic>\u2009\u00a0=\u00a0\u20090.418) and severe COVID\u201019 (<jats:italic>r<jats:sub>g<\/jats:sub><\/jats:italic>\u2009\u00a0=\u00a0\u20090.314). Furthermore, the MR analysis demonstrated a unidirectional causal effect of genetic predisposition to GERD on COVID\u201019 outcomes, including hospitalized COVID\u201019 (odds ratio [OR]: 1.33, 95% confidence interval [CI]: 1.27\u20131.44, <jats:italic>p<\/jats:italic>\u00a0=\u00a09.17e\u00a0\u2212\u00a012) and severe COVID\u201019 (OR: 1.27, 95% CI: 1.18\u20131.37, <jats:italic>p<\/jats:italic>\u00a0=\u00a01.20e\u00a0\u2212\u00a005). Additionally, GERD and both COVID\u201019 conditions shared one genomic locus with lead\u2010SNPs rs1011407 and rs1123573, corresponding to the transcription factor BCL11A. Colocalization analysis further demonstrated a significant positive correlation between genome\u2010wide association study and expression quantitative trait locus (eQTL) abnormalities, including rs1011407 (eQTL_<jats:italic>p<\/jats:italic>\u00a0=\u00a02.35e\u00a0\u2212\u00a007) and rs1123573 (eQTL_<jats:italic>p<\/jats:italic>\u00a0=\u00a02.74e\u00a0\u2212\u00a005). Molecular pathway analysis indicated that GERD might promote the progression of COVID\u201019 by inducting immune\u2010activated and inflammation\u2010related pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings confirm that genetically determined GERD may increase the susceptibility to hospitalized\/severe COVID\u201019. The shared genetic loci and the potential molecular pathways offer valuable insights into causal connections between GERD and COVID\u201019.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12584","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T11:23:54Z","timestamp":1731410634000},"page":"54-65","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastroesophageal reflux disease increases predisposition to severe COVID\u201019: Insights from integrated Mendelian randomization and genetic analysis"],"prefix":"10.1111","volume":"89","author":[{"given":"Jingjing","family":"Pan","sequence":"first","affiliation":[{"name":"Department of Microbiology Zhejiang Provincial Centers for Disease Control and Prevention  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology Zhejiang Provincial Centers for Disease Control and Prevention  Hangzhou China"},{"name":"Zhejiang Key Laboratory of Public Health Detection and Pathogenesis Research  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2144\/fsoa-2023-0042"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-023-02638-7"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.586308"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.2023.2257458"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28431"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.28107"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3211"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21758"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i24.3502"},{"key":"e_1_2_11_11_1","first-page":"195","article-title":"The effects of the COVID\u201019 pandemic on community respiratory virus activity","volume":"21","author":"Chow E. 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