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We aimed to investigate whether pharmacogenomic variation contributes to the risk of bleeding during DOAC treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Cases were recruited from reports of bleeding sent to the Swedish Medical Products Agency (<jats:italic>n<\/jats:italic>\u2009=\u2009129, 60% men, 93% Swedish, 89% on factor Xa inhibitors) and compared with population controls (<jats:italic>n<\/jats:italic>\u2009=\u20094891) and a subset matched for exposure to DOACs (<jats:italic>n<\/jats:italic>\u2009=\u2009353). We performed a genome-wide association study, with analyses of candidate single nucleotide polymorphisms (SNPs) and candidate gene set analyses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Forty-four cases had major, 37 minor, and 48 clinically relevant non-major (CRNM) bleeding. When cases were compared with matched controls, <jats:italic>BAIAP2L2<\/jats:italic> rs142001534 was significantly associated with any bleeding and major\/CRNM bleeding (<jats:italic>P<\/jats:italic>\u2009=\u20094.66\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup> and <jats:italic>P<\/jats:italic>\u2009=\u20093.28\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>, respectively). The candidate SNP <jats:italic>CYP3A5<\/jats:italic> rs776746 was significantly associated with major and major\/CRNM bleeding (<jats:italic>P<\/jats:italic>\u2009=\u20090.00020 and <jats:italic>P<\/jats:italic>\u2009=\u20090.00025, respectively), and <jats:italic>ABCG2<\/jats:italic> rs2231142 was nominally associated with any bleeding (<jats:italic>P<\/jats:italic>\u2009=\u20090.01499). Rare coding variants in the candidate gene <jats:italic>VWF<\/jats:italic> were significantly associated with any bleeding (<jats:italic>P<\/jats:italic>\u2009=\u20090.00296).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>\n              <jats:italic>BAIAP2L2<\/jats:italic>, <jats:italic>CYP3A5<\/jats:italic>, <jats:italic>ABCG2<\/jats:italic>, and <jats:italic>VWF<\/jats:italic> may be associated with bleeding in DOAC-treated patients. The risk estimates of the candidate variants in <jats:italic>CYP3A5<\/jats:italic> and <jats:italic>ABCG2<\/jats:italic> were in the same direction as in previous studies. The Von Willebrand Factor gene (<jats:italic>VWF<\/jats:italic>) is linked to hereditary bleeding disorders, while there is no previous evidence of bleeding associated with <jats:italic>BAIAP2L2.<\/jats:italic>\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00228-025-03821-x","type":"journal-article","created":{"date-parts":[[2025,3,23]],"date-time":"2025-03-23T01:09:50Z","timestamp":1742692190000},"page":"771-783","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome-wide association study of direct oral anticoagulants and their relation to bleeding"],"prefix":"10.1007","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7631-7376","authenticated-orcid":false,"given":"Sofia","family":"Attelind","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2152-4343","authenticated-orcid":false,"given":"Niclas","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6368-2622","authenticated-orcid":false,"given":"Mia","family":"Wadelius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3465-3280","authenticated-orcid":false,"given":"P\u00e4r","family":"Hallberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"3821_CR1","unstructured":"The European Public Assessment Reports Summary of Product Characteristics (2025) Available from the European Medicines Agency Web Page: https:\/\/www.ema.europa.eu\/en\/medicines. 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