Evidence that low socioeconomic position accentuates genetic susceptibility to obesity

Jess Tyrrell; Andrew R Wood; Ryan M Ames; Hanieh Yaghootkar; Robin Beaumont; Samuel E Jones; Marcus A Tuke; Katherine S Ruth; Rachel M Freathy; George Davey-Smith; Stephane Joost; Idris Guessous; Anna Murray; David P Strachan; Zoltan Kutalik; Michael N Weedon; Timothy M Frayling

doi:10.1101/074054

bioRxiv · 10.1101/074054

Evidence that low socioeconomic position accentuates genetic susceptibility to obesity

Jess Tyrrell·Andrew R Wood·Ryan M Ames·Hanieh Yaghootkar·Robin Beaumont·Samuel E Jones·Marcus A Tuke·Katherine S Ruth·Rachel M Freathy·George Davey-Smith·Stephane Joost·Idris Guessous·Anna Murray·David P Strachan·Zoltan Kutalik·Michael N Weedon·Timothy M Frayling

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Abstract

Susceptibility to obesity in todays environment has a strong genetic component. Lower socioeconomic position (SEP) is associated with a higher risk of obesity but it is not known if it accentuates genetic susceptibility to obesity. We aimed to use up to 120,000 individuals from the UK Biobank study to test the hypothesis that measures of socioeconomic position accentuate genetic susceptibility to obesity. We used the Townsend deprivation index (TDI) as the main measure of socioeconomic position, and a 69-variant genetic risk score (GRS) as a measure of genetic susceptibility to obesity. We also tested the hypothesis that interactions between BMI genetics and socioeconomic position would result in evidence of interaction with individual measures of the obesogenic environment and behaviours that correlate strongly with socioeconomic position, even if they have no obesogenic role. These measures included self-reported TV watching, diet and physical activity, and an objective measure of activity derived from accelerometers. We performed several negative control tests, including a simulated environment correlated with BMI but not TDI, and sun protection use. We found evidence of gene-environment interactions with TDI (Pinteraction=3x10-10) such that, within the group of 50% living in the most relatively deprived situations, carrying 10 additional BMI-raising alleles was associated with approximately 3.8 kg extra weight in someone 1.73m tall. In contrast, within the group of 50% living in the least deprivation, carrying 10 additional BMI-raising alleles was associated with approximately 2.9 kg extra weight. We also observed evidence of interaction between sun protection use and BMI genetics, suggesting that residual confounding may result in evidence of non-causal interactions. Our findings provide evidence that relative social deprivation best captures aspects of the obesogenic environment that accentuate the genetic predisposition to obesity in the UK.

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Jess Tyrrell, Andrew R Wood, Ryan M Ames, Hanieh Yaghootkar, Robin Beaumont, Samuel E Jones, Marcus A Tuke, Katherine S Ruth, Rachel M Freathy, George Davey-Smith, Stephane Joost, Idris Guessous, Anna Murray, David P Strachan, Zoltan Kutalik, Michael N Weedon, Timothy M Frayling. 2016-09-13. Evidence that low socioeconomic position accentuates genetic susceptibility to obesity. https://doi.org/10.1101/074054

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