Heart and lungs

One in five men 'carries heart risk gene'

“Men can inherit heart disease from their father,” BBC News has reported. The broadcaster said that a specific version of the Y chromosome, a genetic structure passed from father to son, can raise a man’s heart disease risk by 50%.

This story is based on research that examined variation in the Y chromosome, a Y-shaped bundle of genetic material that makes a foetus develop into a male. Only men have a Y chromosome, and researchers thought that it may account for some of the variation in rates of heart disease between men and women. The researchers looked at the genetic variation in this chromosome in over 3,000 unrelated men, grouped them based on common variations, and then looked at associations between genetic type and risk of coronary artery disease. They found that in men with one particular variation, the odds of developing heart disease were 56% higher than in men from the other main genetic groups identified. This increase was independent of known risk factors for heart disease, including lifestyle and economic factors.

The results suggest that the genetics of the Y chromosome may contribute to a man’s heart disease risk. However, this does not diminish the role of lifestyle and socioeconomic factors, many of which can be modified. The lifestyle changes required to reduce heart disease risk, such as not smoking, are well known and apply to everyone regardless of their genetic make-up.

Where did the story come from?

The study was carried out by researchers from the Universities of Leicester, Glasgow, Leeds and Cambridge, King’s College London and other universities and institutes in Australia, France and Germany. The research was funded by the British Heart Foundation.

The study was published in the peer-reviewed medical journal The Lancet.

This research was covered appropriately by the media. The Independent, for example, emphasised that the results do not mean that men should ignore heart-healthy lifestyle advice based on their genetic risk factors. Genetics only contributes to part of a man’s risk of developing heart disease, and adopting a healthier lifestyle can play a key part in preventing major cardiovascular problems.

What kind of research was this?

Human cells carry 23 pairs of chromosomes. These bundles of DNA together contain a person’s full genetic code. Among them is one pair of chromosomes that determines gender, known as the sex chromosomes. We all carry at least one X-shaped sex chromosome. Women carry a second X chromosome and men instead have a shorter Y chromosome. So women have an XX combination, and men carry an XY combination.

As well as determining sex, the Y chromosome has also been linked to the cardiovascular system. In this study, researchers used a variety of techniques to look at the role of the Y chromosome in cardiovascular health. The research was performed as a series of case-control studies that used data from three separate studies:

  • cross-sectional study – a type of study that looks at various factors at a single point in time
  • prospective clinical trial – a type of study where participants are assigned a treatment or medication and then followed over time to see how they compare to participants using no treatment or an alternative treatment (in this case the trial involved people using statins, a type of cholesterol-lowering medication)
  • genome-wide association study – a type of study that looks for patterns linking people’s genetic make-up to their risk of a particular disease (in this case it aimed to identify genetic variations that lead to developing coronary artery disease, or CAD)

What did the research involve?

The researchers examined the association between variation in the Y chromosome and risk of CAD. The study included 3,233 unrelated British men who were enrolled in one of three ongoing studies. Participants were either:

  • cases – those who had a validated history of CAD or who developed CAD during the course of the original studies, or
  • controls – participants who were matched to the cases based on age group and other factors

Both cases and controls had their genetic information mapped.

The researchers sorted the men into subgroups, called “haplogroups”, according to genetic variation on their Y chromosomes. There are 13 major European haplogroups, each descended from different common genetic ancestors. The participants in these studies were found to belong to nine of these 13 major groups. The researchers then determined how the odds of having or developing heart disease varied across these main haplogroups.

The researchers adjusted their analysis to account for factors associated with heart disease, including age, blood pressure, body mass index, cholesterol levels, blood sugar levels, a history of diabetes, smoking status, alcohol consumption, and socioeconomic, education and employment status.

What were the basic results?

The study showed that:

  • 17% of the men (both cases and controls) in the first study belonged to an ancestral group called haplogroup I. In the second study, 14.5% of the men belonged to this group.
  • Men in haplogroup I had a 56% increased odds of developing coronary artery disease compared to men in any other genetic group (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.24 to 1.97, p=0.0002).
  • Further analysis revealed that this increased risk was independent of other known risk factors. After calculations were carried out to account for these established factors, being in haplogroup I was the most significant predictor of heart disease.
  • When analysing data from the genome-wide association study, the researchers found that, compared to the other haplogroups, men in haplogroup I had genetic differences in genes involved in immunity and inflammation responses.

How did the researchers interpret the results?

The researchers said that of all the main European Y chromosome lineages, “haplogroup I is associated with significantly increased risk of coronary artery disease compared to other ancient lineages”, and that this may be due to a difference in genes related to immunity and the inflammation response.


The results of this study indicate that a specific genetic variation on the Y chromosome is associated with an increased risk of coronary artery disease (CAD). However, heart disease is a complicated condition with a wide variety of risk factors, including some that can be modified.

While genetic variation on the Y chromosome has been identified as a risk factor in this study, it is unlikely to be a predictor of heart disease on its own. The researchers themselves highlight that single risk factors are common in people with and without CAD, and that any single factor (either genetic or non-genetic) is unlikely to predict an individual’s risk of developing the disease. In a positive step, many news sources prominently stated that the Y chromosome is likely to account for only part of a man’s risk.

The researchers also say that their results need to be validated by further prospective studies, which would presumably examine participants’ Y chromosome status and lifestyle factors and then follow them over time to see whether they developed CAD. According to the researchers, future research could help explain how genetic variation puts groups at risk by examining the role of differences in the immune and inflammatory responses. They also say that this finding may lead to the identification of targets for future CAD treatments. However, this would be a long way off.

While this research gives an insight into genetic variation and its role in CAD, it is unlikely to play an immediate part in addressing CAD in the UK. First, men are unlikely to know their specific haplogroup, so are unlikely to know whether they may be at increased risk of CAD. Second, there are many risk factors for CAD, and individuals cannot alter genetic factors. On the other hand, several lifestyle factors can be modified to try to reduce the risk of heart disease.

While no single factor can predict whether a person will develop CAD, people can reduce their risk by not smoking, eating healthy food, exercising regularly and maintaining a healthy weight.

NHS Attribution