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

BackgroundThere 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).MethodsWe 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.ResultsAfter 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.ConclusionsIndividuals 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.

Diet Quality and Food Prices Modify Associations between Genetic Susceptibility to Obesity and Adiposity Outcomes

“…Reduced prices of low-energy dense foods may provide motivation to purchase and subsequently consume these foods, which may be intrinsically less appealing to individuals with higher polygenic risk for obesity. A recent study reported an interaction between genetic risk to obesity and proximity to fast-food outlets on BMI [13]. Although the food environment was evaluated with a different measure, the result adds support to our findings of a moderating effect of the food environment on genetic susceptibility to obesity.…”

“…Indeed, previous studies have reported that adherence to healthy dietary patterns and limiting consumption of sugar sweetened beverages and fried food might attenuate the genetic risk associated with elevated BMI [10][11][12]. One recent study reported a significant interaction between genetic risk to obesity and proximity to fast-food outlets on BMI [13]; however, no study has evaluated the interactions between everyday exposures to food cues in the in-store retail food environment and genetic susceptibility to obesity on diet and anthropometric outcomes. Some of the variants implicated in genetic risk for obesity are involved in neurobehavioral circuits related to dopamine reward and food cue responsivity, suggesting that exposures to in-store retailer food cue stimuli may affect ingestive behavior in distinct ways according to genetic background.…”

Investigating childhood maltreatment as a modifier of genetic risk for cardiovascular disease in the UK Biobank

“…Previous studies have typically only tested the additive scale for interaction. 15,16,19,30 Because effect modification can occur on either the additive scale or the multiplicative scale, we analysed both scales. 18,19 Relevance for public health…”

“…14 PGSs have previously been employed to assess gene*environment interactions or effect modifications for cardiovascular traits, including for educational achievement, neighbourhood and obesogenic environments. [15][16][17] Identifying these effects may help to understand the relationship between early life environmental exposures and CVD risk in adult life.…”

Sex and genetic specific effects on behavioral, but not metabolic, responses to a high fat diet in heterogeneous stock rats

“…Importantly, however, gene-environment interactions have been seen in humans [67][68][69][70][71][72] , but there has been controversy around which environmental factors play a role. In fact, Tyrell et al 73 recently identified multiple environmental factors that interacted with obesogenic alleles to affect susceptibility to obesity in humans, but, similar to our findings, "Western" diet was not found to be a significant factor, bringing into question these earlier findings 73 .…”