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This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis,<jats:italic>ETV6, BDKRB2, MME<\/jats:italic>, and<jats:italic>PRKCQ<\/jats:italic>were nominally associated with angioedema (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), but did not pass Bonferroni correction for multiple testing (<jats:italic>p<\/jats:italic>\u2009&lt;\u20092.89\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (<jats:italic>KCNMA1<\/jats:italic>) gene on chromosome 10 were significantly associated with angioedema (<jats:italic>p<\/jats:italic>\u2009&lt;\u20095\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). Whilst the top<jats:italic>KCNMA1<\/jats:italic>hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05\u20132.50,<jats:italic>p<\/jats:italic>\u2009=\u20090.030). Associated<jats:italic>KCNMA1<\/jats:italic>variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in<jats:italic>KCNMA1<\/jats:italic>is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in<jats:italic>KCNMA1<\/jats:italic>or other genes contribute to the risk of ACEi- and ARB-induced angioedema.<\/jats:p>","DOI":"10.1038\/s41397-020-0165-2","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T00:04:00Z","timestamp":1582243440000},"page":"770-783","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment"],"prefix":"10.1038","volume":"20","author":[{"given":"Eva Rye","family":"Rasmussen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P\u00e4r","family":"Hallberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina V.","family":"Baranova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niclas","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malgorzata","family":"Karawajczyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Cavalli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cyrielle","family":"Maroteau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abirami","family":"Veluchamy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunilla","family":"Islander","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svante","family":"Hugosson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ingrid","family":"Terreehorst","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-8669","authenticated-orcid":false,"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pia","family":"Norling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Erik","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Kohnke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Christine","family":"Syv\u00e4nen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moneeza K.","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chim C.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7315-7899","authenticated-orcid":false,"given":"Patrik K. 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