{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:37:53Z","timestamp":1790804273650,"version":"4.1.0"},"reference-count":31,"publisher":"American Medical Association (AMA)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2023,1,17]]},"abstract":"Importance<\/jats:title>An increased risk of venous thromboembolism (VTE) has been reported in men with an additional sex chromosome. The association between other sex chromosome aneuploidies and VTE is not well characterized.<\/jats:p><\/jats:sec>Objective<\/jats:title>To determine if sex chromosome aneuploidy is associated with VTE.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>Retrospective cohort study of sex chromosome aneuploidy and VTE, performed by analyzing X- and Y-chromosome dosage and VTE incidence in 642\u202f544 individuals from 2 population-scale biobanks: the US Geisinger MyCode Community Health Initiative (N\u2009=\u2009154\u202f519) and the UK Biobank (N\u2009=\u2009488\u202f025); analysis was limited to participants self-identified as White because of inadequate sample sizes for other race and ethnicity groups. A total of 108\u202f461 unrelated MyCode participants with electronic health record follow-up ranging from September 1996 to December 2020 and 418\u202f725 unrelated British and Irish UK Biobank participants who attended the baseline assessment between March 2006 and October 2010, with follow-up extending to November 2020, were included in analyses of VTE.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Sex chromosome aneuploidies.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Individuals with 1 primary inpatient VTE diagnosis, 2 primary outpatient VTE diagnoses, or a self-reported VTE diagnosis were defined as VTE cases. P<\/jats:italic> values were adjusted for multiple comparisons.<\/jats:p><\/jats:sec>Results<\/jats:title>Identification of sex chromosome aneuploidy was undertaken among 642\u202f544 individuals aged 18 to 90 years. Identification of a diagnosis of VTE was undertaken among 108\u202f461 unrelated MyCode participants (65\u202f565 [60.5%] female; mean age at last visit, 58.0 [SD, 17.6] years; median follow-up, 15.3 [IQR, 9.7] years) and among 418\u202f725 unrelated UK Biobank participants (224\u202f695 [53.7%] female; mean age at baseline interview, 56.9 [SD, 8.0] years; median follow-up, 12.0 [IQR, 1.6] years). Among MyCode participants, during 10 years of follow-up, 17 incident VTE events per 1353 person-years were detected among those with supernumerary sex chromosome aneuploidy (1.3% per person-year) compared with 2060 per 816\u202f682 person-years among those with 46,XX or 46,XY (0.25% per person-year) (hazard ratio, 5.4 [95% CI, 3.4-8.7]; 10-year risk difference, 8.8% [95% CI, 4.2%-14.0%]; P<\/jats:italic>\u2009&amp;lt;\u2009.001). Among UK Biobank participants, during 10 years of follow-up, 16 incident VTE events per 3803 person-years were detected among those with supernumerary sex chromosome aneuploidy (0.42% per person-year) compared with 4491 per 3\u202f970\u202f467 person-years among those with 46,XX or 46,XY (0.11% per person-year) (hazard ratio, 4.1 [95% CI, 2.5-6.7]; 10-year risk difference, 3.7% [95% CI, 1.4%-5.9%]; P<\/jats:italic>\u2009&amp;lt;\u2009.001).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>Adults with supernumerary sex chromosome aneuploidies compared with 2 sex chromosomes had a small but statistically significant increased risk of VTE. Further research is needed to understand the clinical implications of this association.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jama.2022.23897","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T16:10:26Z","timestamp":1673971826000},"page":"235","source":"Crossref","is-referenced-by-count":16,"title":["Association of Supernumerary Sex Chromosome Aneuploidies With Venous Thromboembolism"],"prefix":"10.1001","volume":"329","author":[{"given":"Alexander S. 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