{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T04:35:37Z","timestamp":1792298137229,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T00:00:00Z","timestamp":1470182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Gastroesophageal reflux disease (<jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>), the regurgitation of gastric acids often accompanied by heartburn, affects up to 20% of the general population. Genetic predisposition is suspected from twin and family studies but gene\u2010hunting efforts have so far been scarce and no conclusive genome\u2010wide study has been reported. We exploited data available from general population samples, and studied self\u2010reported reflux symptoms in relation to genome\u2010wide single nucleotide polymorphism (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>) genotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a <jats:styled-content style=\"fixed-case\">GWAS<\/jats:styled-content> meta\u2010analysis of three independent population\u2010based cohorts from Sweden, Finland, and <jats:styled-content style=\"fixed-case\">UK<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> cases (n=2247) and asymptomatic controls (n=4503) were identified using questionnaire\u2010derived symptom data. Upon stringent quality controls, genotype data for more than 2.5M markers were used for association testing. Bioinformatic characterization of genomic regions associated with <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> included gene\u2010set enrichment analysis (<jats:styled-content style=\"fixed-case\">GSEA<\/jats:styled-content>), in silico prediction of genetic risk effects on gene expression, and computational analysis of drug\u2010induced gene expression signatures using Connectivity Map (<jats:styled-content style=\"fixed-case\">cM<\/jats:styled-content>ap).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results<\/jats:title><jats:p>We identified 30 <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> suggestive risk loci (P\u22645\u00d710<jats:sup>\u22125<\/jats:sup>), with concordant risk effects in all cohorts, and predicted functional effects on gene expression in relevant tissues. <jats:styled-content style=\"fixed-case\">GSEA<\/jats:styled-content> revealed involvement of <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> risk genes in biological processes associated with the regulation of ion channel and cell adhesion. From <jats:styled-content style=\"fixed-case\">cM<\/jats:styled-content>ap analysis, omeprazole had significant effects on <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content> risk gene expression, while antituberculosis and anti\u2010inflammatory drugs scored highest among the repurposed compounds.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We report a large\u2010scale genetic study of <jats:styled-content style=\"fixed-case\">GERD<\/jats:styled-content>, and highlight genes and pathways that contribute to further our understanding of its pathogenesis and therapeutic opportunities.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12923","type":"journal-article","created":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T05:07:06Z","timestamp":1470200826000},"source":"Crossref","is-referenced-by-count":24,"title":["A meta\u2010analysis of reflux genome\u2010wide association studies in 6750 Northern Europeans from the general population"],"prefix":"10.1111","volume":"29","author":[{"given":"F.","family":"Bonfiglio","sequence":"first","affiliation":[{"name":"Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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V.","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"M\u00e4nnikk\u00f6","sequence":"additional","affiliation":[{"name":"Center for Life Course Health Research University of Oulu Oulu Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Nordenstedt","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Zucchelli","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bresso","sequence":"additional","affiliation":[{"name":"Department of Biosciences and Nutrition Karolinska Institutet Stockholm Sweden"},{"name":"Department of Medicine Solna Karolinska Institutet Center for Digestive Diseases Karolinska University Hospital Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Twin Research &amp; Genetic Epidemiology King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Tornblom","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Nutrition Institute of Medicine Sahlgrenska Academy University of Gothenburg Gothenburg Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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