Genetic risk of obesity as a modifier of associations between neighbourhood environment and body mass index: an observational study of 335 046 UK Biobank participants

Abstract

Background: There is growing recognition that recent global increases in obesity are the product of a complex interplay between genetic and environmental factors. However, in gene-environment studies of obesity, 'environment' usually refers to individual behavioural factors that influence energy balance, whereas more upstream environmental factors are overlooked. We examined gene-environment interactions between genetic risk of obesity and two neighbourhood characteristics likely to be associated with obesity (proximity to takeaway/fast-food outlets and availability of physical activity facilities).

Methods: We used data from 335 046 adults aged 40-70 in the UK Biobank cohort to conduct a population-based cross-sectional study of interactions between neighbourhood characteristics and genetic risk of obesity, in relation to body mass index (BMI). Proximity to a fast-food outlet was defined as distance from home address to nearest takeaway/fast-food outlet, and availability of physical activity facilities as the number of formal physical activity facilities within 1 km of home address. Genetic risk of obesity was operationalised by weighted Genetic Risk Scores of 91 or 69 single nucleotide polymorphisms (SNP), and by six individual SNPs considered separately. Multivariable, mixed-effects models with product terms for the gene-environment interactions were estimated.

Results: After accounting for likely confounding, the association between proximity to takeaway/fast-food outlets and BMI was stronger among those at increased genetic risk of obesity, with evidence of an interaction with polygenic risk scores (p=0.018 and p=0.028 for 69-SNP and 91-SNP scores, respectively) and in particular with a SNP linked to MC4R (p=0.009), a gene known to regulate food intake. We found very little evidence of gene-environment interaction for the availability of physical activity facilities.

Conclusions: Individuals at an increased genetic risk of obesity may be more sensitive to exposure to the local fast-food environment. Ensuring that neighbourhood residential environments are designed to promote a healthy weight may be particularly important for those with greater genetic susceptibility to obesity.

Keywords: dietary patterns; malnutrition.

Figure 1

Associations between neighbourhood variables and BMI in the highest and lowest quintiles of genetic risk, based on (A) 69-SNP Genetic Risk Score, and (B) 91-SNP Genetic Risk Score. BMI, body mass index; PA, physical activity; SNP, single-nucleotide polymorphism,

Figure 2

Associations between neighbourhood variables and BMI according to number of risk alleles at individual SNPs where p_interaction<0.10 (rs1558902 and rs6567160 for fast-food proximity; rs13021737 for availability of PA facilities). BMI, body mass index; PA, physical activity; SNP, single-nucleotide polymorphism.