Discrimination Exposure and Polygenic Risk for Obesity in Adulthood: Testing Gene-Environment Correlations and Interactions

Introduction: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene × environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation). Methods: This was an observational study of 4,102 white/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination Scale items. Polygenic risk scores (PRSs) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Results: We found that greater PRS-BMI was significantly associated with more reports of discrimination (β = 0.04 ± 0.02; p = 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively. Conclusion: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population level.