Interaction between the FTO gene, body mass index and depression: meta-analysis of 13701 individuals

Abstract

BackgroundDepression 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.AimsTo confirm these findings by investigating the FTO polymorphism rs9939609 in new cohorts, and subsequently in a meta-analysis.MethodThe 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.ResultsIn 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.ConclusionsThis 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.

Maternal early pregnancy obesity and depressive symptoms during and after pregnancy

“…According to a recent systematic review of genome-wide association and candidate gene studies pleiotropic genes, such as the FTO gene, may underlie (Amare et al 2017), but findings are however, inconsistent (Walter et al 2015). Also interactions between genotype, such as the FTO gene, depression and BMI have been reported (Clarke et al 2015;Rivera et al 2017). On the other hand, both depression (Osborne et al 2016;Chen et al 2017;Edvinsson et al 2017) and BMI (Dick et al 2014;Ligthart et al 2016) Behavioral mechanisms may also be involved, including sleep problems and pain that may be aggravated in higher BMI pregnancies and that may induce more depressed feelings.…”

The role of mRNA m6A methylation in the nervous system

“…The homozygous mutation of FTO gene can reduce the brain capacity of healthy elderly people, increase the susceptibility to brain atrophy during aging, and even affect the brain volume of adolescents [117,118]. The genetic polymorphism of FTO is related to attention-deficit/hyperactivity disorder (ADHD), Alzheimer's disease and depression [119][120][121][122][123][124]. Whether it is as demethylase that affects these diseases, is worthy of further study.…”

Preliminary findings on the relationship between gender, FTO rs9939609, leptin & ghrelin levels and eating behaviours of adults

“…In addition, the situation of being diagnosed with depression of the individuals was investigated based on a personal declaration in this study. In one study, it was reported that the BMI of individuals with depression who had risk allele was 2.2% higher and increased the effect of FTO [27]. Therefore, it is considered that it will be useful to evaluate this situation by considering the depression status in the future studies.…”