Dataset Information

Gene-obesogenic environment interactions in the UK Biobank study.

ABSTRACT:

Background

Previous studies have suggested that modern obesogenic environments accentuate the genetic risk of obesity. However, these studies have proven controversial as to which, if any, measures of the environment accentuate genetic susceptibility to high body mass index (BMI).

Methods

We used up to 120 000 adults from the UK Biobank study to test the hypothesis that high-risk obesogenic environments and behaviours accentuate genetic susceptibility to obesity. We used BMI as the outcome and a 69-variant genetic risk score (GRS) for obesity and 12 measures of the obesogenic environment as exposures. These measures included Townsend deprivation index (TDI) as a measure of socio-economic position, TV watching, a 'Westernized' diet and physical activity. We performed several negative control tests, including randomly selecting groups of different average BMIs, using a simulated environment and including sun-protection use as an environment.

Results

We found gene-environment interactions with TDI (Pinteraction = 3 × 10 -10 ), self-reported TV watching (Pinteraction = 7 × 10 -5 ) and self-reported physical activity (Pinteraction = 5 × 10 -6 ). 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 1.73 m 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. The interactions were weaker, but present, with the negative controls, including sun-protection use, indicating that residual confounding is likely.

Conclusions

Our findings suggest that the obesogenic environment accentuates the risk of obesity in genetically susceptible adults. Of the factors we tested, relative social deprivation best captures the aspects of the obesogenic environment responsible.

SUBMITTER: Tyrrell J

PROVIDER: S-EPMC5837271 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND:Gene-obesogenic environment interactions influence body mass index (BMI) across the life course; however, limited research examines how these interactions may differ by race and sex. METHODS:Utilizing mixed-effects models, we examined the interaction effects of a polygenic risk score (PGS) generated from BMI-associated single-nucleotide polymorphisms, and environmental factors, including age, physical activity, alcohol intake, and childhood socioeconomic status on measured longitudinal BMI from the Health and Retirement Study (HRS). HRS is a population representative survey of older adults in the United States. This study used a subsample of genotyped Black (N?=?1796) and White (N?=?4925) men and women (50-70 years) with measured BMI. RESULTS:Higher PGS was associated with higher BMI. The association between PGS and BMI weakened as individuals aged among White men (Pinteraction?=?0.0383) and White women (Pinteraction?=?0.0514). The mean BMI difference between the 90th and 10th PGS percentile was 4.25?kg/m2 among 50-year-old White men, and 3.11?kg/m2 among the 70 years old's, i.e., a 1.14?kg/m2 (95% CI: -0.27, 2.82) difference. The difference among 50- and 70-year-old White women was 1.34?kg/m2 (95% CI: 0.09, 2.60). In addition, the protection effect of physical activity was stronger among White women with higher PGS (Pinteraction?=?0.0546). Vigorous physical activity (compared with never) was associated with 1.66?kg/m2 (95% CI: 1.06, 2.29) lower mean BMI among those in the 90th PGS percentile, compared with 0.83?kg/m2 (95% CI: 0.37, 1.29) lower among those in the 10th PGS percentile. Interactions were also observed between both PGS and alcohol intake among White men (Pinteraction?=?0.0034) and women (Pinteraction?=?0.0664) and Black women (Pinteraction?=?0.0108), and PGS and childhood socioeconomic status among White women (Pinteraction?=?0.0007). CONCLUSIONS:Our findings reinforce the importance of physical activity among those with an elevated genetic risk; additionally, other detected interactions may underscore the influence of broader social environments on obesity-promoting genes.