Twice as many men carry an extra sex chromosome as previously thought, according to researchers who called for more genetic testing to identify people at greater risk of related medical problems.

Research on more than 200,000 men enrolled with the UK Biobank suggests that about one in 500 in the general population has an extra X or Y chromosome, double the number found in earlier work, though only a fraction are likely to be aware of it.

While most men have one X and one Y chromosome, some are born XXY or XYY, putting them at increased risk of health issues ranging from type 2 diabetes, blocked blood vessels and chronic obstructive pulmonary disease (COPD), a lung condition, the study found.

“We were surprised at how common this is,” said Prof Ken Ong, a paediatric endocrinologist at the MRC epidemiology unit at Cambridge and a senior author on the study. “It had been thought to be pretty rare.”

Working with colleagues at the University of Exeter, the Cambridge team examined DNA from 207,067 men of European ancestry aged from 40 to 70 years old. They identified 231 men with an extra X chromosome and 143 men with an extra Y chromosome. Those enrolled with the UK Biobank tend to be healthier than average, but from the data, the scientists estimate that 1 in 500 men in the general population carry an extra X or Y chromosome.

Among the men flagged up in the study, published in Genetics in Medicine, only 23% of those XXY and 0.7% of those XYY had a known diagnosis of an extra chromosome, suggesting there was little awareness of the condition.

Men with an additional X chromosome are often diagnosed when it has an impact on puberty and fertility, though it is also linked to higher body fat, cognitive problems and personality disorders. In the study, XXY men had substantially lower testosterone than XY men, a threefold greater risk of delayed puberty, and a fourfold higher risk of being childless. The effects of an extra Y chromosome are less well understood. XYY men tend to be taller as boys and adults, but appear to have normal reproductive function.

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Previous research suggests that about 1 in 1,000 women carry an additional X chromosome, which can lead to similar effects, ranging from faster growth until puberty, delayed language development and reduced IQ compared with their XX peers.

Analysis of the men’s health records found that carrying either extra sex chromosome raised the risks of several medical conditions. Compared with XY men, carrying an extra sex chromosome tripled the risk of type 2 diabetes and blocked blood vessels in the lungs, quadrupled the risk of COPD, and raised the risk of blocked veins sixfold, the researchers found. It is unclear why the extra chromosomes have such an impact, and why it is similar regardless of the chromosome that is duplicated.

“We should be embracing more genetic tests, particularly around delayed puberty and infertility, and also some men presenting with diabetes and clotting problems,” Ong said. “Some of these conditions do prompt genetic tests, but doctors probably aren’t looking for this. We need to encourage broader genetic tests when patients present with these conditions.”


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