Key result
Depression significantly increases the effect of the FTO polymorphism rs9939609 on body mass index, with risk allele carriers who have depression showing a 2.2% higher BMI per risk allele.
Why the study?
Does depression moderate the effect of the FTO gene polymorphism rs9939609 on body mass index in White European individuals?
Meta-Analysis (n=13,701)
Yes
Does depression moderate the effect of the FTO gene polymorphism rs9939609 on body mass index in White European individuals?
Effect estimate: β = 0.12
p-value: p=0.027
This meta-analysis demonstrates that depression significantly amplifies the BMI-increasing effect of the FTO rs9939609 risk allele, highlighting a shared genetic and biological interaction between obesity and depression.
Suggests a shared biological interaction between obesity and depression; leaves open whether targeted psychiatric interventions could mitigate genetic.
Background Depression and obesity are highly prevalent, and major impacts on public health frequently co-occur. Recently, we reported that having depression moderates the effect of the FTO gene, suggesting its implication in the association between depression and obesity. Aims To confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis. Method The sample consists of 6902 individuals with depression and 6799 controls from three replication cohorts and two original discovery cohorts. Linear regression models were performed to test for association between rs9939609 and body mass index (BMI), and for the interaction between rs9939609 and depression status for an effect on BMI. Fixed and random effects meta-analyses were performed using METASOFT. Results In the replication cohorts, we observed a significant interaction between FTO , BMI and depression with fixed effects meta-analysis (β=0.12, P = 2.7 × 10 −4 ) and with the Han/Eskin random effects method ( P = 1.4 × 10 −7 ) but not with traditional random effects (β = 0.1, P = 0.35). When combined with the discovery cohorts, random effects meta-analysis also supports the interaction (β = 0.12, P = 0.027) being highly significant based on the Han/Eskin model ( P = 6.9 × 10 −8 ). On average, carriers of the risk allele who have depression have a 2.2% higher BMI for each risk allele, over and above the main effect of FTO. Conclusions This meta-analysis provides additional support for a significant interaction between FTO , depression and BMI, indicating that depression increases the effect of FTO on BMI. The findings provide a useful starting point in understanding the biological mechanism involved in the association between obesity and depression.
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Rivera et al. (2017) conducted a meta-analysis in Depression and obesity (n=13,701). FTO polymorphism rs9939609 and depression vs. Controls without depression was evaluated on Interaction between rs9939609 and depression status for an effect on BMI (β = 0.12, p=0.027). Depression significantly increases the effect of the FTO polymorphism rs9939609 on body mass index, with risk allele carriers who have depression showing a 2.2% higher BMI per risk allele.
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