Genetic Links between Depression and Obesity Remain Unclear

Studies have shown that major depressive disorder (MDD) has a strong link to genetic factors, and many clinicians and researchers believe the same to be true for obesity.

The recent, large-scale Genetic Investigation of Anthropometric Traits (GIANT) consortium, findings from which were published in the February 2015 edition of Nature, identified many different biological pathways that are important in controlling body weight and fat distribution. It also established a strong genetic connection in neural processes that control appetite and the body’s use of energy.

Other studies have shown that MDD increases the odds for developing obesity, and the condition has been shown to amplify the effect of obesity-related genetic variants on body mass index (BMI). However, the relationship between obesity and certain subtypes of MDD is not well understood. Obesity and MDD appear to share a common genetic architecture, but there are conflicting studies on the actual genetic links between the two. While certain genes — notably the fat-mass- and obesity-associated FTO gene – may be a common genetic indicator of greater possibility for MDD or obesity, there is the possibility that many different single nucleotide polymorphisms (sequence variations in our genetic code) may play a role.

A new study in Translational Psychiatry assessed whether BMI and MDD have an overlapping polygenic architecture using a large population-based cohort: Generation Scotland: the Scottish Family Health Study (GS:SFHS). The authors “hypothesized that the association between BMI polygenic profile scores and BMI would be moderated by the presence of MDD. We also tested whether this extended to current psychological distress or neuroticism by using scores on the General Health Questionnaire (GHQ-28) and the Eysenck personality questionnaire for neuroticism, as these traits are heritable and genetically correlated with MDD in this sample.”

The team found that BMI polygenic profile scores were not significantly associated with MDD or neuroticism; however, an association with GHQ scores was observed at all P-value thresholds.

“Individuals scoring higher on the GHQ were found to carry more BMI-increasing alleles…,” the study authors noted. “There is little evidence for genetic overlap between BMI and MDD in this large population-based cohort using a polygenic profile score approach…BMI polygenic profile scores for BMI were not associated with a lifetime history of MDD in GS:SFHS, and polygenic risk for MDD was not associated with BMI.”

The data did, however, show that MDD status was amplified the effect of BMI polygenic profile scores on BMI. The authors concluded that the genetic overlap between MDD and BMI may be restricted to the FTO gene, or as suggested by earlier research, BMI risk variants may only be relevant for atypical depression.

“There may be genetic overlap between BMI and MDD, but we have greater power to detect an association with GHQ scores due to the trait being continuous versus binary…We also find no association between BMI polygenic profile scores and neuroticism, further suggesting that it is current psychological distress (measured using the GHQ) rather than a tendency to lower mood that overlaps with polygenic risk for BMI,” the team confirmed.

Additional studies are needed to understand the biological mechanisms that cause mood to influence BMI and to more firmly establish a genetic link, if there is one, between obesity and MDD.

“By understanding the relationship between MDD and obesity, we can better understand their mechanisms and develop interventions to reduce their considerable burden on those affected,” the authors concluded.