Researchers from the University of Cambridge collaborated with scientists in Finland and Germany to examine how an extra sex chromosome in men relates to health risks. Their findings indicate that about one in every 500 men carries an additional X or Y chromosome, a genetic variation that appears to increase the likelihood of several health conditions later in life. The researchers reported their observations in a peer‑reviewed article published by Genetics in Medicine, underscoring the importance of understanding how chromosomal differences influence disease risk across populations.
The study drew on records from the UK Biobank, a large repository containing medical and genetic data from more than 200,000 British men aged 40 to 70. In this cohort, 356 individuals were identified as carrying an extra sex chromosome. Because the UK Biobank samples a relatively healthier segment of the population, the investigators concluded that the real prevalence of an extra chromosome among men might lie near one in 500 when accounting for broader population diversity.
Often, clinicians detect the chromosomal anomaly when a man is evaluated for delayed puberty or infertility, but in many cases the individuals themselves are unaware of these genetic variations. The study emphasizes that the presence of an additional X or Y chromosome can go unnoticed for years, highlighting the subtlety with which some genetic differences influence development and health without producing clear, early warning signs.
Detailed analyses revealed distinct patterns by genotype. Men with XXY, the classic Klinefelter profile, showed a markedly higher risk of infertility and a greater likelihood of experiencing delayed puberty. They also tended to have lower testosterone levels, contributing to a range of metabolic and developmental effects. In contrast, those with the XYY genotype did not display the same reproductive challenges, suggesting that different chromosomal configurations carry different risk profiles even within the same broad category of chromosomal aneuploidy.
Beyond reproductive health, the presence of an extra sex chromosome was associated with several other health outcomes. Individuals with an additional chromosome faced a higher probability of metabolic and cardiovascular complications, including type 2 diabetes, where risk appeared increased by up to several fold in comparison with typical male populations. They were also more prone to thrombotic events, such as deep vein thrombosis or pulmonary embolism, and exhibited a greater likelihood of experiencing chronic obstructive pulmonary disease, which can impact daily functioning and quality of life. These associations remained evident even after controlling for common risk factors, pointing to the possible contribution of chromosomal variation to disease pathways independent of lifestyle factors alone.
The authors call for additional research to determine whether broader screening for chromosomal abnormalities in the general population could enable earlier detection and intervention. They note that identifying individuals with this genetic difference might open doors to personalized monitoring and timely lifestyle or medical interventions that could reduce the risk or severity of related conditions over the lifespan. While routine population screening would require careful consideration of ethical, logistical, and cost factors, the study argues that the potential to avert or diminish future health problems makes such exploration worthwhile. The work adds to a growing body of evidence that genetic background can influence multiple-body systems, urging clinicians and researchers to consider chromosomal variation as a component of comprehensive health assessment and risk management.