Evidence that lower socioeconomic position accentuates genetic susceptibility to obesity

Abstract

Susceptibility to obesity in today's 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 BMIraising 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.

Dietary fat and total energy intake modifies the association of genetic profile risk score on obesity: evidence from 48 170 UK Biobank participants

“…The present datawith the most comprehensive genetic profile risk score for obesity available to dateclearly demonstrate that the association of total energy intake, total fat and saturated fat on adiposity outcomes are strongest in those with a high genetic predisposition to obesity. Our finding suggest that fat and total energy intake are other factors which need to be consider, alongside socio-demographic, 31 sleep, 32 physical activity 31,33 and other dietary intake patterns. 11,[13][14][15]31 Evidence of such gene-lifestyle interactions may empower and motivate individuals with high genetic risk for obesity to adopt healthier lifestyle behaviours through knowledge that such behaviour change can be effective in preventing obesity and, therefore, risk of obesity-related non-communicable diseases.…”

“…Our finding suggest that fat and total energy intake are other factors which need to be consider, alongside socio-demographic, 31 sleep, 32 physical activity 31,33 and other dietary intake patterns. 11,[13][14][15]31 Evidence of such gene-lifestyle interactions may empower and motivate individuals with high genetic risk for obesity to adopt healthier lifestyle behaviours through knowledge that such behaviour change can be effective in preventing obesity and, therefore, risk of obesity-related non-communicable diseases. [34][35][36] In conclusion, despite the fact that this 93-SNP genetic profile risk score was robustly associated with BMI and WC, our results show that lower levels of total fat and saturated fat intake attenuates the strength of the association between genetic predisposition to obesity with BMI and waist circumference.…”

Obesity pandemic: causes, consequences, and solutions—but do we have the will?

“…Bray et al recently described the relationship between genes and the environment by stating, ''genes load the gun-the environment pulls the trigger'' (13). Tyrrell et al (14) recently analyzed data from 120,000 adults in a large national data base using BMI as the outcome and genetics (a 69-variant genetic risk score for obesity) and self-reported estimates of nine behavioral measures, such as TV watching, Western diet, and physical inactivity, as exposures. More TV watching and less physical activity were strongly associated with a higher BMI.…”

Communicating evidence about the environment’s role in obesity and support for government policies to tackle obesity: a systematic review with meta-analysis

“…Scientific and policy communities now widely acknowledge that environmental factors are the driving force behind the high and rising rates of obesity worldwide (Brandkvist et al, 2019;Davies, 2019;Swinburn et al, 2011;Tyrrell et al, 2017). Reducing the health and economic burden of obesity would be helped by large scale changes to our physical and fiscal environments that enable healthier food consumption and increased physical activity (Hollands et al, 2019;Marteau et al, 2012).…”