Can Obesity Genes Affect Your Mood?

A bidirectional association between obesity and depression has been evidenced in longitudinal studies. In a meta-analysis of 15 longitudinal studies (N=55,745), obesity (body mass index [BMI] ≥ 30 kg/m2) at baseline was associated with a 1.55-fold increase in the incidence of depression at follow-up. Conversely, depression at baseline was associated with a 1.58-fold increase in the incidence of obesity over time. Environmental factors may account for part of this association (eg, weight increase as a consequence of antidepressant drug use). However, a heritability study suggested that shared genetic architecture may also account, at least in part, for the association between obesity and depression.

My colleagues and I previously reported an inverse association between depression and a gene variant linked to obesity; the obesity-risk FTO rs9939609 A gene variant was associated with an 8% decrease in the risk for depression in 6,561 people with depression and 21,932 controls. In a recent article published in The Journal of Clinical Psychiatry, we studied the effects of 21 additional obesity-predisposing gene variants on depression in the EpiDREAM study (3,209 people with depression and 14,195 controls), and we made two important discoveries. First, the TAL1 rs2984618 obesity risk allele was associated with an 11% higher risk of depression. Second, we identified an ethnic-specific pattern of association between an obesity gene variant and depression. While the BDNF rs1401635 obesity risk allele was associated with a 12% lower risk of depression in non-European populations, the same obesity risk allele was associated with an 11% higher risk of depression in European populations.

To render the picture more complex, five single-nucleotide polymorphisms in the FTO gene have been shown to interact with depression status to increase BMI in 2 independent European populations. Additionally, an interaction between the well-established obesity/type 2 diabetes–predisposing gene TCF7L2 and BMI in people with bipolar disorder has been recently reported.

Altogether, these recent discoveries demonstrate that susceptibility to obesity and depression share common molecular roots. In the long run, this research is expected to improve the prevention and treatment of depression and obesity, two frequent diseases on the rise at the global level.

Financial disclosure:Dr Meyre has no personal affiliations with any commercial interest to disclose.​