{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:25:54Z","timestamp":1790115954183,"version":"4.0.1"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,11,19]],"date-time":"2021-11-19T00:00:00Z","timestamp":1637280000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014653","name":"Manchester Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014653","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["RG\/14\/5\/30893"],"award-info":[{"award-number":["RG\/14\/5\/30893"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["eBioMedicine"],"published-print":{"date-parts":[[2021,12]]},"DOI":"10.1016\/j.ebiom.2021.103728","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T06:39:04Z","timestamp":1638427144000},"page":"103728","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":12,"special_numbering":"C","title":["Genome-Wide association between EYA1 and Aspirin-induced peptic ulceration"],"prefix":"10.1016","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9245-9510","authenticated-orcid":false,"given":"Stephane","family":"Bourgeois","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Carr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crispin O.","family":"Musumba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Penrose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Celestine","family":"Esume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Jorgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Eunice","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Mark","family":"Pritchard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panos","family":"Deloukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2021.103728_bib0001","first-page":"183","article-title":"Recent trends in the prevalence of low-dose aspirin use for primary and secondary prevention of cardiovascular disease in the United States, 2012-2015","volume":"5","author":"Stuntz","year":"2017","journal-title":"Prevent. Med. Rep."},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0002","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1007\/s00296-011-2263-6","article-title":"A turbulent decade for NSAIDs: update on current concepts of classification, epidemiology, comparative efficacy, and toxicity","volume":"32","author":"Conaghan","year":"2012","journal-title":"Rheumatol Int"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0003","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1097\/00045391-200007020-00008","article-title":"Gastrointestinal complications of prescription and over-the-counter nonsteroidal anti-inflammatory drugs: a view from the ARAMIS database. Arthritis, Rheumatism, and Aging Medical Information System","volume":"7","author":"Singh","year":"2000","journal-title":"Am J Ther"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103728_bib0004","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/aje\/kwh005","article-title":"Risk of uncomplicated peptic ulcer among users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs","volume":"159","author":"Garcia Rodriguez","year":"2004","journal-title":"Am J Epidemiol"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0005","doi-asserted-by":"crossref","first-page":"161","DOI":"10.7326\/0003-4819-136-2-200201150-00016","article-title":"Aspirin for the primary prevention of cardiovascular events: a summary of the evidence for the U.S. preventive services task force","volume":"136","author":"Hayden","year":"2002","journal-title":"Ann Intern Med"},{"issue":"10093","key":"10.1016\/j.ebiom.2021.103728_bib0006","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/S0140-6736(17)30770-5","article-title":"Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study","volume":"390","author":"Li","year":"2017","journal-title":"Lancet"},{"issue":"7456","key":"10.1016\/j.ebiom.2021.103728_bib0007","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1136\/bmj.329.7456.15","article-title":"Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients","volume":"329","author":"Pirmohamed","year":"2004","journal-title":"BMJ"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0008","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1136\/gut.52.4.600","article-title":"Non-steroidal anti-inflammatory drugs: overall risks and management. Complementary roles for COX-2 inhibitors and proton pump inhibitors","volume":"52","author":"Hawkey","year":"2003","journal-title":"Gut"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103728_bib0009","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/pds.561","article-title":"Ulcer complications associated with anti-inflammatory drug use. What is the extent of the disease burden?","volume":"10","author":"Langman","year":"2001","journal-title":"Pharmacoepidemiol Drug Saf"},{"issue":"24","key":"10.1016\/j.ebiom.2021.103728_bib0010","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJM199906173402407","article-title":"Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs","volume":"340","author":"Wolfe","year":"1999","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ebiom.2021.103728_bib0011","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2021.684162","article-title":"Pharmacogenomics of NSAID-induced upper gastrointestinal toxicity","volume":"12","author":"McEvoy","year":"2021","journal-title":"Front Pharmacol"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0012","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1038\/sj.bjp.0705623","article-title":"Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use","volume":"141","author":"Martinez","year":"2004","journal-title":"Br J Pharmacol"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0013","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1053\/j.gastro.2007.05.025","article-title":"Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms","volume":"133","author":"Pilotto","year":"2007","journal-title":"Gastroenterology"},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0014","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1046\/j.0306-5251.2001.01398.x","article-title":"Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration?","volume":"51","author":"Martin","year":"2001","journal-title":"Br J Clin Pharmacol"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0015","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1080\/17425255.2020.1744563","article-title":"An update on the pharmacogenomics of NSAID metabolism and the risk of gastrointestinal bleeding","volume":"16","author":"Macias","year":"2020","journal-title":"Expert Opin Drug Metab Toxicol"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0016","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/clpt.2012.215","article-title":"CYP2C19*17 gain-of-function polymorphism is associated with peptic ulcer disease","volume":"93","author":"Musumba","year":"2013","journal-title":"Clin Pharmacol Ther"},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0017","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/j.1365-2036.2009.04086.x","article-title":"Review article: cellular and molecular mechanisms of NSAID-induced peptic ulcers","volume":"30","author":"Musumba","year":"2009","journal-title":"Aliment Pharmacol Ther"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103728_bib0018","first-page":"373","article-title":"Association between genetic polymorphisms in the cyclooxygenase-1 gene promoter and peptic ulcers in Japan","volume":"20","author":"Arisawa","year":"2007","journal-title":"Int J Mol Med"},{"issue":"12","key":"10.1016\/j.ebiom.2021.103728_bib0019","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1007\/s10620-006-9475-8","article-title":"Effect of a specific cyclooxygenase-gene polymorphism (A-842G\/C50T) on the occurrence of peptic ulcer hemorrhage","volume":"51","author":"van Oijen","year":"2006","journal-title":"Dig Dis Sci"},{"key":"10.1016\/j.ebiom.2021.103728_bib0020","doi-asserted-by":"crossref","first-page":"860","DOI":"10.3389\/fphar.2020.00860","article-title":"Influence of polymorphisms involved in platelet activation and inflammatory response on aspirin-related upper gastrointestinal bleeding: a case-control study","volume":"11","author":"Mallah","year":"2020","journal-title":"Front Pharmacol"},{"issue":"20","key":"10.1016\/j.ebiom.2021.103728_bib0021","doi-asserted-by":"crossref","first-page":"2741","DOI":"10.1093\/bioinformatics\/btm443","article-title":"A genotype calling algorithm for the Illumina BeadArray platform","volume":"23","author":"Teo","year":"2007","journal-title":"Bioinformatics"},{"issue":"7311","key":"10.1016\/j.ebiom.2021.103728_bib0022","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1038\/nature09298","article-title":"Integrating common and rare genetic variation in diverse human populations","volume":"467","author":"International HapMap","year":"2010","journal-title":"Nature"},{"issue":"3","key":"10.1016\/j.ebiom.2021.103728_bib0023","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: a tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.ebiom.2021.103728_bib0024","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"Gigascience"},{"issue":"2","key":"10.1016\/j.ebiom.2021.103728_bib0025","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nmeth.1785","article-title":"A linear complexity phasing method for thousands of genomes","volume":"9","author":"Delaneau","year":"2012","journal-title":"Nat Methods"},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1000529","article-title":"A flexible and accurate genotype imputation method for the next generation of genome-wide association studies","volume":"5","author":"Howie","year":"2009","journal-title":"PLoS Genet"},{"issue":"7571","key":"10.1016\/j.ebiom.2021.103728_bib0027","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Genomes Project","year":"2015","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0028","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1111\/j.1360-0443.1993.tb02093.x","article-title":"Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol Consumption\u2013II","volume":"88","author":"Saunders","year":"1993","journal-title":"Addiction"},{"key":"10.1016\/j.ebiom.2021.103728_bib0029","unstructured":"R Development Core Team. R: A language and environment for statistical computing 2011."},{"issue":"7","key":"10.1016\/j.ebiom.2021.103728_bib0030","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1038\/ng2088","article-title":"A new multipoint method for genome-wide association studies by imputation of genotypes","volume":"39","author":"Marchini","year":"2007","journal-title":"Nat Genet"},{"issue":"18","key":"10.1016\/j.ebiom.2021.103728_bib0031","doi-asserted-by":"crossref","first-page":"2336","DOI":"10.1093\/bioinformatics\/btq419","article-title":"LocusZoom: regional visualization of genome-wide association scan results","volume":"26","author":"Pruim","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.ebiom.2021.103728_bib0032","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1186\/1471-2105-11-288","article-title":"GWAMA: software for genome-wide association meta-analysis","volume":"11","author":"Magi","year":"2010","journal-title":"BMC Bioinformatics"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0033","doi-asserted-by":"crossref","first-page":"R36","DOI":"10.1186\/gb-2013-14-4-r36","article-title":"TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions","volume":"14","author":"Kim","year":"2013","journal-title":"Genome Biol"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0034","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat Methods"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0035","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/tpj.2015.47","article-title":"Pharmacogenomic variants have larger effect sizes than genetic variants associated with other dichotomous complex traits","volume":"16","author":"Maranville","year":"2016","journal-title":"Pharmacogenomics J"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0036","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1038\/ng.1109","article-title":"A genome-wide association study identifies two susceptibility loci for duodenal ulcer in the Japanese population","volume":"44","author":"Tanikawa","year":"2012","journal-title":"Nat Genet"},{"issue":"6","key":"10.1016\/j.ebiom.2021.103728_bib0037","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/humu.20048","article-title":"Branchio-oto-renal syndrome: the mutation spectrum in EYA1 and its phenotypic consequences","volume":"23","author":"Chang","year":"2004","journal-title":"Hum Mutat"},{"issue":"14","key":"10.1016\/j.ebiom.2021.103728_bib0038","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1002\/ajmg.a.31561","article-title":"Branchio-oto-renal syndrome","volume":"143A","author":"Kochhar","year":"2007","journal-title":"Am J Med Genet A"},{"issue":"6964","key":"10.1016\/j.ebiom.2021.103728_bib0039","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nature02083","article-title":"Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis","volume":"426","author":"Li","year":"2003","journal-title":"Nature"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103728_bib0040","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ydbio.2013.07.019","article-title":"Abrogation of Eya1\/Six1 disrupts the saccular phase of lung morphogenesis and causes remodeling","volume":"382","author":"Lu","year":"2013","journal-title":"Dev Biol"},{"issue":"7","key":"10.1016\/j.ebiom.2021.103728_bib0041","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1002\/dvdy.24282","article-title":"Eya-six are necessary for survival of nephrogenic cord progenitors and inducing nephric duct development before ureteric bud formation","volume":"244","author":"Xu","year":"2015","journal-title":"Dev Dyn"},{"issue":"7238","key":"10.1016\/j.ebiom.2021.103728_bib0042","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1038\/nature07849","article-title":"Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions","volume":"458","author":"Cook","year":"2009","journal-title":"Nature"},{"issue":"4","key":"10.1016\/j.ebiom.2021.103728_bib0043","doi-asserted-by":"crossref","first-page":"e34806","DOI":"10.1371\/journal.pone.0034806","article-title":"The EYA tyrosine phosphatase activity is pro-angiogenic and is inhibited by benzbromarone","volume":"7","author":"Tadjuidje","year":"2012","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.ebiom.2021.103728_bib0044","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/s41467-021-21280-7","article-title":"GWAS of peptic ulcer disease implicates Helicobacter pylori infection, other gastrointestinal disorders and depression","volume":"12","author":"Wu","year":"2021","journal-title":"Nat Commun"}],"container-title":["eBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396421005223?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396421005223?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T16:38:26Z","timestamp":1764866306000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396421005223"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":44,"alternative-id":["S2352396421005223"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103728","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2021,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Genome-Wide association between EYA1 and Aspirin-induced peptic ulceration","name":"articletitle","label":"Article Title"},{"value":"eBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2021.103728","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"103728"}}