Fat mass and obesity-associated (FTO) rs9939609 polymorphism modifies the relationship between body mass index and affective symptoms through the life course: a prospective birth cohort study

Shinsuke Koike,Rebecca Hardy,Andrew Wong,Marcus Richards

doi:10.1038/s41398-018-0110-1

Abstract

Although bi-directional relationships between high body mass index (BMI) and affective symptoms have been found, no study has investigated the relationships across the life course. There has also been little exploration of whether the fat mass and obesity-associated (FTO) rs9939609 single-nucleotide polymorphism (SNP) is associated with affective symptoms and/or modifies the relationship between BMI and affective symptoms. In the MRC National Survey of Health and Development (NSHD), 4556 participants had at least one measure of BMI and affective symptoms between ages 11 and 60–64 years. A structural equation modelling framework was used with the BMI trajectory fitted as latent variables representing BMI at 11, and adolescent (11–20 years), early adulthood (20–36 years) and midlife (36–53 years) change in BMI. Higher levels of adolescent emotional problems were associated with greater increases in adult BMI and greater increases in early adulthood BMI were associated with higher subsequent levels of affective symptoms in women. The rs9939609 risk variant (A allele) from 2469 participants with DNA genotyping at age 53 years showed mostly protective effect modification of these relationship. Increases in adolescent and early adulthood BMI were generally not associated with, or were associated with lower levels, of affective symptoms in the FTO risk homozygote (AA) group, but positive associations were seen in the TT group. These results suggest bi-directional relationships between higher BMI and affective symptoms across the life course in women, and that the relationship could be ameliorated by rs9939609 risk variant.

Highlights

Obesity and affective symptoms are common conditions; the life-time prevalence of each is estimated to be greater than 20% in the general population in highincome and middle-income countries[1,2]
Male participants had higher body mass index (BMI) compared to female at ages 11–43 years, and fewer affective symptoms at all ages (Table 1)
The model had the main effects of sex on BMI and affective symptoms, as well as sex interactions on the relationship between BMI and affective symptoms (Supplementary Fig. s1)

Summary

Introduction

Obesity and affective symptoms are common conditions; the life-time prevalence of each is estimated to be greater than 20% in the general population in highincome and middle-income countries[1,2]. Both increase the risk of physical and psychiatric diseases such as. Multiple possible explanations have been proposed for the relationship between higher body weight and depressive symptoms Shared biological mechanisms such as immunological deficiencies, oxidative stress, neurotransmitter imbalance, and hypothalamic–pituitary–adrenal (HPA) imbalance are likely to play a role[13,14,15]. Whereas men with adolescent symptoms which continued into adulthood had lower BMI in adolescence and across adulthood

Methods

Results

Conclusion