Mortality and Obesity Among US Older Adults: The Role of Polygenic Risk

Objectives: To examine the relationship between obesity and mortality as a function of polygenic risk for obesity among older U.S. adults. Method: Using data from the 1994-2014 Health and Retirement Study in conjunction with genome-wide data, we evaluated the risk of mortality as a function of obesity classification, an individual's polygenic risk score (PGS) for obesity, and their interaction, stratified by sex. We conducted our analyses using cox proportional hazard models. Results: Among those with an average PGS for obesity (8,143 [68.8%]), obese I (hazard ratio [HR] = 0.79, p = .336) adults show no difference in their risk for mortality and obese II/III (HR = 3.17, p = .000) adults present higher risk of mortality relative to non-obese adults. The interaction of obesity classification and PGS suggests that obese II/III respondents with low PGS in the total sample (HR = 2.71, p = .006) and among women (HR = 3.02, p = .023) are at significantly higher risk of death when compared to obese II/III respondents with average or high PGS. Discussion: We posit that these findings suggest that the pathway to obesity, in this case, more socio-behavioral rather than genetic, may influence subsequent risk of death in older adults. We suggest that practitioners and population researchers be mindful of these pathways as to better identify and understand mortality risk.