Background Characteristics of the built environment such as neighbourhood fast-food outlet exposure, are increasingly recognised as risk factors for unhealthy diet and obesity. Obesity also has a genetic component, with common genetic variants explaining a substantial proportion of population-level obesity susceptibility. However, it is not known whether and to what extent associations between fast-food outlet exposure and body weight are modified by genetic predisposition to obesity.

Methods We used data from the Fenland study, a population-based sample of 12,435 UK adults (mean age 48.6 years). We derived a genetic risk score associated with BMI (BMI-GRS) from 96 BMI-associated single nucleotide polymorphisms. Neighbourhood fast-food exposure was defined as quartiles of counts of outlets around the home address. We used multivariable regression models to estimate the associations of each exposure, independently and in combination, with measured BMI, overweight and obesity, and investigated interactions.

Results We found independent associations between BMI-GRS and risk of overweight (RR=1.34, 95% CI 1.23-1.47) and obesity (RR=1.73, 95% CI 1.55-1.93), and between fast-food outlet exposure and risk of obesity (highest vs lowest quartile RR=1.58, 95% CI 1.21-2.05). There was no evidence of an interaction of fast-food outlet exposure and genetic risk on BMI (P=0.09), risk of overweight (P=0.51), or risk of obesity (P=0.27). The combination of higher BMI-GRS and highest fast-food outlet exposure was associated with 2.70 (95% CI 1.99-3.66) times greater risk of obesity.

Conclusions Our study demonstrated independent associations of both genetic obesity risk and neighbourhood fast-food outlet exposure with adiposity. These important drivers of the obesity epidemic have to date been studied in isolation. Neighbourhood fast-food outlet exposure remains a potential target of policy intervention to prevent obesity and promote the public’s health.