Meal Frequencies Modify the Effect of Common Genetic Variants on Body Mass Index in Adolescents of the Northern Finland Birth Cohort 1986

Anne Jääskeläinen,Marjo-Riitta Järvelin,Jaana Laitinen,Philippe Froguel,Marjukka Kolehmainen,Markku J Savolainen,Stéphane Cauchi,Ursula Schwab,Marika Kaakinen,Shengxu Li

doi:10.1371/journal.pone.0073802

Abstract

Recent studies suggest that meal frequencies influence the risk of obesity in children and adolescents. It has also been shown that multiple genetic loci predispose to obesity already in youth. However, it is unknown whether meal frequencies could modulate the association between single nucleotide polymorphisms (SNPs) and the risk of obesity. We examined the effect of two meal patterns on weekdays –5 meals including breakfast (regular) and ≤4 meals with or without breakfast (meal skipping) – on the genetic susceptibility to increased body mass index (BMI) in Finnish adolescents. Eight variants representing 8 early-life obesity-susceptibility loci, including FTO and MC4R, were genotyped in 2215 boys and 2449 girls aged 16 years from the population-based Northern Finland Birth Cohort 1986. A genetic risk score (GRS) was calculated for each individual by summing the number of BMI-increasing alleles across the 8 loci. Weight and height were measured and dietary data were collected using self-administered questionnaires. Among meal skippers, the difference in BMI between high-GRS and low-GRS (<8 and ≥8 BMI-increasing alleles) groups was 0.90 (95% CI 0.63,1.17) kg/m2, whereas in regular eaters, this difference was 0.32 (95% CI 0.06,0.57) kg/m2 (p interaction = 0.003). The effect of each MC4R rs17782313 risk allele on BMI in meal skippers (0.47 [95% CI 0.22,0.73] kg/m2) was nearly three-fold compared with regular eaters (0.18 [95% CI -0.06,0.41] kg/m2) (p interaction = 0.016). Further, the per-allele effect of the FTO rs1421085 was 0.24 (95% CI 0.05,0.42) kg/m2 in regular eaters and 0.46 (95% CI 0.27,0.66) kg/m2 in meal skippers but the interaction between FTO genotype and meal frequencies on BMI was significant only in boys (p interaction = 0.015). In summary, the regular five-meal pattern attenuated the increasing effect of common SNPs on BMI in adolescents. Considering the epidemic of obesity in youth, the promotion of regular eating may have substantial public health implications.

Highlights

Prevention of obesity in children has been proposed as a public health priority to combat the obesity epidemic
The results indicate that regular meal frequency attenuates genetic predisposition to increased body mass index (BMI) in terms of both single gene variants (FTO rs1421085 and MC4R rs17782313) and a multiplelocus indicator
Carrying both of the risk-conferring alleles of rs17782313 at the MC4R locus was associated with a greater BMI (22.2 [95% confidence intervals (CI) 21.6, 22.9] kg/m2) compared with the other two genotypes (TT: 21.1 [95% CI 21.0, 21.2] kg/m2 and CT: 21.3 [95% CI 21.1, 21.5] kg/m2)

Summary

Introduction

Prevention of obesity in children has been proposed as a public health priority to combat the obesity epidemic. The etiology of childhood obesity is multifaceted with both lifestyle and genetic factors playing a role in the susceptibility to excessive weight gain [1]. Numerous obesity-related genetic loci have been identified through genome-wide association studies (GWAS) [2]. Among the well-established genetic factors that influence weight development already in childhood are the common single nucleotide polymorphisms (SNPs) in the FTO and MC4R gene regions [7,8,9,10]. In relation to childhood and adolescent obesity, it has been proposed that the impact of overall eating patterns may be more significant than that of single foods or nutrients [11]. Some studies indicate that higher meal frequencies and regular breakfast consumption are inversely associated with obesity in youth [12,13], while some studies have failed to detect any association [14,15]

Methods

Results

Conclusion