Depression Augments Genetic Risks for Excessive Weight Gain, UK Biobank Study Finds
Depression increases the likelihood of gaining excess weight and aggravates the role that genetics plays in people with a high body mass index (BMI), a large study from the U.K. reports.
MC4R, a gene involved in genetic disorders of obesity, seems to be an important link between depression and obesity, and may be a valuable treatment target, its investigators said.
The study, “Depression increases the genetic susceptibility to high body mass index: Evidence from UK Biobank,” was published in the journal Depression & Anxiety.
While obesity continues to become more and more common globally, scientists still have a long way to go in understanding the multiple genetic factors thought to underlie excess weight.
Genome‐wide association studies — which look for associations between genetic variations (mutations) and traits — have identified over 700 mutations related to BMI. Yet, these factors only explain 5% of the variability in BMI seen in the population.
Interaction between genetic variants and lifestyle factors are a likely explanation for other heritable cases, adding further complexity. For instance, diet and physical activity are known to lessen high BMI risk in genetically predisposed individuals.
Another possible factor that may modify genetic susceptibility to excess weight is depression. Depressed individuals tend to be less physically active and have worse dietary habits. Some research also suggests that obesity may both be a risk factor for and a consequence of depression.
To explore this, researchers used a large dataset corresponding to 251,125 UK Biobank participants (ages 37–73). The team also investigated if genetic susceptibility to high BMI is modified by having depression.
Results supported such link. Individuals with a history of depression — either with only a single episode, recurrent depressive disorder, or hospital-diagnosed depression — had higher BMI and a greater prevalence of obesity than those who had never been depressed
The group with a greater genetic predisposition to high BMI, as determined by calculating a genetic risk score comprising 73 mutations, showed a greater frequency of depression. Importantly, this genetic risk contributed more to excess weight among individuals with depression, suggesting an interaction between both factors.
In other words, if two individuals carried the same risk for excess weight, the one who was depressed is more likely to have a higher weight than the one who was not.
For people of average height who carried 10 genetic risk variants for obesity, this difference corresponded to 3.4 kg (about 7.5 lbs.) extra weight in depressed individuals, compared to 2.8 kg (about 6 lbs.) in those without depression.
Among the mutations involved, the effects were stronger for a variant near MC4R, a gene well-known to regulate appetite.
“Our study provides genetic evidence for causal effect of depression on BMI,” the researchers wrote. Their finding also “provides support for a possible role of MC4R in the link between depression and obesity.”
“This result may strengthen the case for MC4R as a potential target for pharmaceutical interventions for obesity,” they added.