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We investigated whether X\u2010linked variation\u2014common (minor allele frequency [MAF] \u22650.01) and rare (MAF &lt;0.01)\u2014was associated with sporadic TAD in three cohorts of European descent (<jats:italic>Discovery<\/jats:italic>: 364 cases, 874 controls; <jats:italic>Replication<\/jats:italic>: 516 cases, 440,131 controls, and <jats:italic>ARIC<\/jats:italic> [Atherosclerosis Risk in Communities study]: 753 cases, 2247 controls). For analysis of common variants, we applied a sex\u2010stratified logistic regression model followed by a meta\u2010analysis of sex\u2010specific odds ratios. Furthermore, we conducted a meta\u2010analysis of overlapping common variants between the <jats:italic>Discovery<\/jats:italic> and <jats:italic>Replication<\/jats:italic> cohorts. For analysis of rare variants, we used a sex\u2010stratified optimized sequence kernel association test model. Common variants results showed no statistically significant findings in the <jats:italic>Discovery<\/jats:italic> cohort. An intergenic common variant near <jats:italic>SPANXN1<\/jats:italic> was statistically significant in the <jats:italic>Replication<\/jats:italic> cohort (<jats:italic>p<\/jats:italic>\u2009=\u20091.81\u2009\u00d7\u200910<jats:sup>\u22128<\/jats:sup>). The highest signal from the meta\u2010analysis of the <jats:italic>Discovery<\/jats:italic> and <jats:italic>Replication<\/jats:italic> cohorts was a <jats:italic>ZNF182<\/jats:italic> intronic common variant (<jats:italic>p<\/jats:italic>\u2009=\u20093.5\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>). In rare variants results, <jats:italic>RTL9<\/jats:italic> reached statistical significance (<jats:italic>p<\/jats:italic>\u2009=\u20095.15\u2009\u00d7\u200910<jats:sup>\u22125<\/jats:sup>). Although most of our results were statistically insignificant, our analysis is the most comprehensive X\u2010chromosome association analysis of sporadic TAD to date.<\/jats:p>","DOI":"10.1002\/ajmg.a.63644","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T02:15:10Z","timestamp":1714529710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["X\u2010linked genetic associations in sporadic thoracic aortic dissection"],"prefix":"10.1002","volume":"194","author":[{"given":"Fadi I.","family":"Musfee","sequence":"first","affiliation":[{"name":"Human Genetics Center, Department of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston  Houston Texas USA"},{"name":"Department of Epidemiology Fay W. 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Center, Department of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston  Houston Texas USA"},{"name":"Center for Precision Health, School of Biomedical Informatics The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongchuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine McGovern Medical School, The University of Texas Health Science Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siddharth K.","family":"Prakash","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine McGovern Medical School, The University of Texas Health Science Center  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaunak Sanjay","family":"Adkar","sequence":"additional","affiliation":[{"name":"Veterans Affairs Palo Alto Healthcare System  Palo Alto California USA"},{"name":"Department of Surgery Stanford University School of Medicine  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan L.","family":"Grove","sequence":"additional","affiliation":[{"name":"Human Genetics Center, Department of Epidemiology Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryan Bohyun","family":"Choi","sequence":"additional","affiliation":[{"name":"Veterans Affairs Palo Alto Healthcare System  Palo Alto California USA"},{"name":"Department of Surgery Stanford University School of Medicine  Palo Alto California 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