A large study of hundreds of thousands of individual genomes has established the rate of occurrence of an extra sex chromosome. People assigned male at birth usually have XY sex chromosomes, but the new work highlights how many have XYY or XXY instead: around one in 500.

In the study, published in Genetics in Medicine, the anonymized genetic, lifestyle, and health information of over 200,000 self-identified men aged 40 to 70 were collected from the UK Biobank. Researchers discovered 356 men with either an extra X chromosome – known as Klinefelter syndrome – or an extra Y chromosome – Jacob’s syndrome.

The analysis showed that older men with extra sex chromosomes have a higher risk of diabetes, atherosclerosis, and blood clots. The data suggest that men with either XXY or XYY were three times more likely to experience pulmonary embolism, and four times as likely to suffer from chronic obstructive pulmonary disease than men with XY chromosomes. Their risk of developing venous thrombosis (blood clots) was six times higher and they were three times more likely to develop type 2 diabetes.

“Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this. This extra chromosome means that they have substantially higher risks of a number of common metabolic, vascular, and respiratory diseases – diseases that may be preventable,” first author Yajie Zhao, a graduate researcher at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, said in a statement.

The extra chromosome doesn’t generally lead to any obvious or unique changes, which means people with these conditions are often not diagnosed or misdiagnosed. In the databank, 213 men had the XXY configuration. Men with this condition can experience delayed puberty and infertility, although most do not know they have it. Fewer than one in four (23 percent) of the sample was aware before the analysis.

There were 143 men with Jacob's syndrome (XYY) in the analysis. Men with an extra Y chromosome tend to be taller as boys and adults than XY men. Only one of the 143 people in the study had previously known of having an extra Y chromosome.

“Our study is important because it starts from the genetics and tells us about the potential health impacts of having an extra sex chromosome in an older population, without being biased by only testing men with certain features as has often been done in the past,” Professor Anna Murray, at the University of Exeter said.

The work continues to highlight the complexity of human genetics, especially with regard to sex. Sex, just like gender, cannot be considered a binary. A fascinating piece last year told the story of a woman successfully giving birth despite most of her cells having XY chromosomes.