A small, but statistically significant, association was found between supernumerary sex chromosome aneuploidy and the risk of developing venous thromboembolism (VTE). This is according to the findings of a study published in JAMA.

Sex chromosome aneuploidy, which involves an atypical X or Y chromosome number, is not an uncommon condition. However, it can be linked to a variety of differences, ranging from stature to biochemical variation, with possible implications for health. Prior research had suggested possible links between sex chromosome aneuploidies and VTE risk.

This study was a retrospective analysis examining X- and Y-chromosome dosage in relation to VTE incidence. Baseline and follow-up data regarding VTE diagnoses were analyzed for 108,461 unrelated individuals with records in the US Geisinger MyCode Community Health Initiative (MyCode) and for 418,725 unrelated individuals with records in the UK Biobank.

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Participants with a sex chromosome aneuploidy were compared with individuals having a 46,XX or 46,XY karyotype for analyses related to VTE incidence. Because of insufficient numbers of participants from varied races and ethnicities for statistical analyses, the researchers limited their analyses to individuals who identified themselves as White.

The MyCode participants had a mean age at last visit of 58.0 years and a median follow-up duration of 15.3 (interquartile range, 9.7) years. The UK Biobank participants had a mean age at baseline interview of 56.9 years and a median follow-up duration of 12.0 (IQR, 1.6) years. Each cohort included 25 individuals who were identified as having a sex chromosome aneuploidy.

In an analysis of VTE incidence with 10-year follow-up, MyCode participants showed a rate of VTE of 1.3 events per 100 person-years among those with supernumerary sex chromosome aneuploidy, whereas the rate for participants with 2 sex chromosomes was 0.25 events per 100 person-years. The difference in these rates corresponded to a hazard ratio (HR) of 5.4 (95% CI, 3.4-8.7) in an analysis adjusted for age, sex, and ancestry.

For the UK Biobank participants, the 10-year VTE rates were 0.42 events per 100 person-years in individuals with supernumerary sex chromosome aneuploidy, compared with 0.11 events per 100 person-years in those with 2 sex chromosomes. The HR for this comparison was 4.1 (95% CI, 2.5-6.8) in an adjusted analysis.

“Adults with supernumerary sex chromosome aneuploidies compared with those having 2 sex chromosomes had a small but statistically significant increased risk of VTE,” the researchers concluded in their report. They highlighted a need for additional research to explore any clinical implications of these findings.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.


Berry ASF, Finucane BM, Myers SM, et al. Association of supernumerary sex chromosome aneuploidies with venous thromboembolism. JAMA. 2023;329(3):235-243. doi:10.1001/jama.2022.23897