Gene-environment interactions in obesity: results from the multi-ethnic cohort EpiDREAM

Abstract

Background: Obesity is now considered to be a global epidemic and gene-environment interaction studies are crucial to understanding the genetic architecture of this disease. The objectives of this research were to (1) review the current evidence of gene-environment interactions in the field of obesity, (2) examine the interactions between obesity predisposing gene variants and physical activity using precise physical activity data and (3) analyze a novel gene-environment interaction between obesity predisposing gene variants and multiple pregnancies.

Methods: The data for the gene-environment interaction analyses were collected from the EpiDREAM study: a prospective cohort including participants of six ethnic backgrounds from 21 countries worldwide. A subset of 17 423 participants with complete genotype and phenotype information was included in the analysis. Obesity predisposing single nucleotide polymorphisms were analyzed independently and as a genetic risk score. General linear models were used to analyze all main effects and interactions.

Results: Physical activity interacted with FTO rs9939609 to modulate BMI (Pinteraction=0.032) and BAI (Pinteraction=3.26 x 10-4). Increased physical activity attenuated the impact of FTO on obesity. Four SNPs displayed significant associations with physical activity: NTRK2 rs1211166 (P=0.015), BDNF rs6265 (P=0.007), BDNF rs1401635 P=0.003) and NPC1 rs1805081 (P=3.52 x 10-4). Multiple pregnancies was significantly associated with BMI (Pinteraction=1.17 x 10-5) BAI (Pinteraction=3.47 x 10-7) and also interacted with FTO rs9939609 to modulate BMI (Pinteraction=0.014). The impact of FTO on BMI was accentuated by multiple pregnancies in the EpiDREAM cohort.

Discussion: Both physical activity and parity have a significant impact on obesity measures and these effects appear to be relevant on a global scale. Our results confirm the physical activity x FTO interaction in a multi-ethnic context and indicate that parity may also interact with FTO polymorphisms.