19 October 2016

Your Genes Are More Important Than Environment In Determining If You Get Fat

Your genes have an impact about seven times as great as your socio-economic status on weight gain among people in the United Kingdom. But, note that the U.K. may lack the extreme deprivations found in other places and thus have less variation due to socio-economic status than the U.S. or less developed countries. 

There are 69 known genetic risk factors for obesity that have been reduced to a genetic risk score. On average, each allele in the score that is present increases the weight of a 5'8" person by 0.737 pounds (in theory an average difference of 50.853 pounds between with no risk alleles, and someone with all of the  risk alleles for a 5'8" person). The weight gain associated with the genetic risk is 7% higher than average for someone in the bottom half of the socio-economic scale, and is 7% lower than average in someone in the top half of the socio-economic scale. (The combined 14% difference from top to bottom is about 1/7th of the total.)
Statement of Purpose: Susceptibility to obesity in today’s environment has a strong genetic component. However, little is known about how genetic susceptibility interacts with modern environments and behaviours to predispose some individuals to obesity whilst others remain slim. Social deprivation is associated with a higher risk of obesity but it is not known if it accentuates genetic susceptibility to obesity. Previous gene-obesogenic environment studies have been limited by the need to perform meta-analyses of many heterogeneous studies and studies have not necessarily corrected for statistical artefacts such as different variances between groups (heteroscedasticity). We aimed to use 120,000 individuals from the UK Biobank study to test the hypothesis that objective measures of relative deprivation in the UK accentuate genetic susceptibility to obesity. 
Methods: We used the Townsend deprivation index (TDI) as a measure of deprivation and a 69-variant genetic risk score (GRS) as a measure of genetic susceptibility to obesity. We tested the association of the genetic risk score with BMI in high and low socioeconomic groups and tested for interactions (using the continuous TDI as an exposure measure). To test the specificity of any apparent interactions we repeated analyses using a simulated environment (that was correlated with BMI in the same way as TDI) as an interaction term and using randomly selected groups of individuals of different BMIs.  
Results: We found evidence of gene-environment interactions with TDI (Pinteraction=3x10-10). Within the 50% of most deprived individuals, carrying 10 additional BMI-raising alleles was associated with approximately 3.8 kg extra weight in someone 1.73m tall. In contrast, within the 50% of least deprived individuals carrying 10 additional BMI-raising alleles was associated with approximately 2.9 kg extra weight. When we used a simulated environment or randomly selected groups of individuals to be of different BMIs, we observed only nominal evidence of apparent interaction, (simulated environment Pinteraction = 0.04; randomly selected groups: Pinteraction=9x10-4) suggesting the interaction was specific to TDI.  
Conclusions: Our findings provide evidence that social deprivation accentuates the genetic predisposition to obesity.

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