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.