Cambridge Researchers Find That One in 500 Men Have an Extra Sex Chromosome, Providing New Precision Medicine Testing Target

High prevalence of previously underreported genetic variation indicates that routine genetic screening may offer a means of preventing diseases before they occur

British researchers at University of Cambridge and University of Exeter have found that one in 500 men have an extra sex chromosome that increases the risk of multiple diseases, making it an ideal precision medicine testing target for identifying genetic risk early and intervening before disease develops.

To conduct their study, the scientists analyzed a genetic database of more than 200,000 men in the United Kingdom. They found that one in 500 of the men had either an extra X chromosome or an extra Y chromosome. This new finding is surprising because the high prevalence of men with an extra sex chromosome had never been tested for or discovered.

The researchers published the full results of their study in Genetics in Medicine, titled, “Detection and Characterization of Male Sex Chromosome Abnormalities in the UK Biobank Study.” 

Extra Chromosomes Known to Increase Risk for Certain Diseases

Yajie Zhao of Cambridge University: Zhao is a PhD student at the University of Cambridge and first author of a chromosome abnormality study in males.
“Even though a significant number of men carry an extra sex chromosome, very few of them are likely to be aware of this,” said Yajie Zhao (above) in a Cambridge University news release. Zhao is a PhD student at the University of Cambridge and first author of the chromosome abnormality study. “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.” (Photo: Cambridge University)

Extra chromosomes can cause disability or death in some cases and be relatively benign in others, depending on the chromosome that is overrepresented. While extra sex chromosomes are not likely to cause a severe disability, they are known to increase risk for type 2 diabetes, blood clots, and heart disease.

The previously-unknown high prevalence of extra sex chromosomes indicates that genetic screening for this abnormality may be helpful. This precision medicine approach would enable physicians to detect the genetic abnormality early, before disease states have developed, and intervene to reduce the individual-specific risks for those patients.

“Genetic testing can detect chromosomal abnormalities fairly easily, so it might be helpful if XXY and XYY were more widely tested for in men who present to their doctor with a relevant health concern,” observed Ken Ong, PhD, a professor at Cambridge’s MRC Epidemiology Unit and a senior author of the study.

“We’d need more research to assess whether there is additional value in wider screening for unusual chromosomes in the general population,” Ong continued, “but this could potentially lead to early interventions to help them avoid the related diseases.”

Genetic Screening for Disease Risk

One of the potential benefits of using a genetic-based screen is that it might detect long-term health risks in all men with extra sex chromosomes, not just in those who have symptoms from it. “Our study is important because it starts from the genetics,” said Anna Murray, PhD, a professor at the University of Exeter and senior author of the study. “[It] 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.”

Genetic screening for diseases that have not yet begun to develop is a concept that is growing in popularity as precision medicine research advances. Another recent study led by Rosalind Eeles, PhD, Professor of Oncogenetics at the Institute of Cancer Research (ICR) London, found that routine genetic testing could detect a risk of cancer in one in four patients and is feasible to implement as part of routine wellness exams.

“We feel that this work could place us at the start of a revolution for healthcare, by helping to pave the way for a future where genomic screening is provided routinely to patients in primary care,” Eeles said in an ICR news release. “Our findings suggest that integrating whole-genome sequencing into primary care could change the way most patients and their families are managed by their GPs.”

Precision medicine research continues to reveal new genetic variations that affect an individual’s risk of disease, but that can allow for treatment to occur before disease develops. While healthcare leaders may benefit from individual advances in precision medicine screening options, it is important to recognize that there is a growing push toward integrating genetic screening into routine patient care. 

—Caleb Williams

Related Information:

Detection and Characterization of Male Sex Chromosome Abnormalities in the UK Biobank Study

One in 500 Men Carry Extra Sex Chromosome, Putting Them at Higher Risk of Several Common Diseases

ASCO 2022: Screening of Patients’ Genomes for GPS to Assess Disease Risk Is ‘Feasible’

Ken Ong, PhD

Rosalind Eeles, PhD

Anna Murray, PhD

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