Detection and characterization of male sex chromosome abnormalities in the UK Biobank study, 2022, Zhao et al

Abstract

Purpose
The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes.

Methods
We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data.

Results
Only 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = –3.8 nmol/L, all P < 2 × 10–8), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P < 7 × 10–6).

Conclusion
KS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking.

Open access, https://www.sciencedirect.com/science/article/pii/S1098360022007778

 

1 in 500 men with extra sex chromosome at higher risk of disease

Researchers have found that around one in 500 men could be carrying an extra X or Y chromosome putting them at increased risk of several common diseases.

In a study published in Genetics in Medicine, researchers at the universities of Cambridge and Exeter analysed genetic data collected on over 200,000 UK men aged 40 to 70.

The data was collected from UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information from half a million UK participants.

They found 356 men who carried either an extra X chromosome or an extra Y chromosome.

https://www.ukri.org/news/1-in-500-men-with-extra-sex-chromosome-at-higher-risk-of-disease/