Genetic variations linked to leanness
The Daily Telegraph reported that “slim people could be at a higher risk of heart disease and diabetes than their flattering figures suggest due to a ‘lean gene’ that masks the dangers.”
This report is based on research that pooled data on genetic information and body fat percentages in over 75,000 people. It found that common genetic variations near to three genes, called FTO, IRS1 and SPRY2, were associated with a 0.14–0.33% lower body fat percentage. Variations near to IRS1 have also been shown to be linked to heart disease and diabetes in previous studies.
This research has identified genetic variations linked to body fat. Although one of these variations may also be linked to heart disease, this does not mean that being lean is bad for you, or that everyone who is slim is at greater risk of heart disease. The genetic variation in question only contributes a small amount to differences in body fat, so has a limited influence on whether a person is slim. Research is also needed to confirm that the IRS1 gene affects heart disease risk.
We cannot change our genetics, and being overweight or obese is known to contribute to a person’s risk of heart disease. Therefore, people should aim to maintain a healthy weight, eat a healthy balanced diet and stay active, whatever their size.
Where did the story come from?
The study was carried out by researchers from the Institute of Metabolic Science in Cambridge and other research centres around the world. It was funded by a large number of organisations, including charities, government agencies and universities. The study was published in the peer-reviewed journal Nature Genetics.
The Daily Telegraph, Daily Mirror and Daily Mail covered this research. They all focused on the link between the IRS1 gene and heart disease and diabetes. However, this was not the focus of the research, which was set up to identify genetic variations linked to body fat percentage. The findings regarding heart disease and diabetes come from other, previous studies. The Telegraph mentioned that the findings “don’t detract from the fact that being overweight is bad for your heart health, so we should still try to stay lean and fit”.
What kind of research was this?
The researchers aimed to identify genetic variations associated with body fat percentage. They say that although several genetic variations linked to a person’s body mass index (BMI) have been identified, these only account for a small amount of variation in BMI. Also, BMI does not distinguish what proportion of a person’s mass is fat. Therefore, the researchers wanted to identify genetic variations that were more directly associated with body fat.
This study was a meta-analysis of data from genome-wide association studies, which are used to identify genetic variations linked to traits or diseases that show complex patterns of inheritance. These traits or diseases appear to be caused by several genes that all have an effect, as well as by the environment. By pooling data from multiple studies, the analysis is better able to detect genetic variations that each have a small effect.
What did the research involve?
The researchers first analysed data from 15 genome-wide association studies that looked at body fat percentage. These studies included data on about 2.5 million genetic variations spread across the DNA in 36,626 people. Of these, 29,069 people were of European descent and 7,557 were of Indo-Asian descent.
The researchers looked at whether any genetic variations were more common in people with higher or lower body fat percentages. This allowed them to identify genetic variations that showed an association with body fat percentage. They looked at the 14 variations that showed the strongest associations in another 39,576 European individuals from 11 studies, to see if they could confirm their results.
The researchers then examined which genes were near the associated genetic variations identified, to see which of them might affect body fat percentage. Further analyses looked at which other related traits these genetic variations were associated with.
What were the basic results?
The researchers identified a genetic variation near the FTO gene that was linked to body fat percentage. The variation near this gene was associated with a 0.33% lower body fat percentage for each copy of this variation a person carried. Previous studies had also linked genetic variations near this gene to fat percentage.
They also found an association between body fat percentage and genetic variations in two areas of DNA that had not previously been associated with this trait. One of the areas contained a gene called IRS1 and the other contained a gene called SPRY2. Both these genes potentially play a role in fat cell biology.
The variation near IRS1 was associated with 0.16% lower body fat percentage for each copy of this variation a person carried. The effect appeared to be stronger in men than women. The variation was not associated with BMI, but was associated with lower levels of “good” (HDL) cholesterol in the blood, and increasing resistance to insulin.
When the researchers tested the activity of the IRS1 gene in subcutaneous fat tissue from a sample of individuals, those tissue samples from people carrying the genetic variant associated with lower body fat percentage showed lower activity of the IRS1 gene. Previous studies have found other genetic variations in this area to be associated with metabolic problems, such as lower levels of HDL cholesterol in the blood and poorer response to insulin, as well as increased risk of diabetes and coronary artery disease.
The variation near SPRY2 was associated with 0.14% lower body fat percentage for each copy of this variation a person carried. This genetic variation appeared to have an effect in Europeans, but not in Indo-Asian people. The variation showed a modest association with BMI, but was not associated with the levels of fats in the blood.
How did the researchers interpret the results?
The researchers concluded that they have identified variations in three areas of the genome that are “convincingly associated with body fat percentage”. They say that their findings “provide new insights” into body fat and insulin resistance.
This large study has identified some genetic variations associated with body fat percentage, and confirmed these in a second large sample of people. The researchers have also identified genes (called FTO, IRS1, and SPRY2) near these variations that could affect body fat. Each of these variations is associated with small changes in body fat mass (0.14–0.33% for each copy of the individual variations). This study used data from mostly Europeans, and the results may not apply to other populations.
Other variations near the IRS1 gene have also been linked to heart disease in previous studies. Further research will need to confirm whether the IRS1 gene influences heart disease risk.
The results of this study do not mean that being lean is bad for you. Being a healthy weight makes a person less likely to develop several diseases, including heart disease, than someone who is overweight or obese. We cannot change our genetics, but maintaining a healthy weight, eating a healthy balanced diet and staying active is the best way to avoid disease and live longer.
More research will undoubtedly be carried out to investigate the roles of these genes in regulating body fat, and whether they also play a role in cardiovascular and metabolic diseases.
- View article: ‘Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile’
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