ABSTRACT
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.
Subject(s)
Life Style , Mortality/trends , Obesity , Social Factors , Body Mass Index , Female , Humans , Male , Middle Aged , Multifactorial Inheritance , Obesity/diagnosis , Obesity/mortality , Proportional Hazards Models , Psychology, Social , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Severity of Illness Index , Sex Factors , United States/epidemiologyABSTRACT
This study evaluates changes in genetic penetrance-defined as the association between an additive polygenic score and its associated phenotype-across birth cohorts. Situating our analysis within recent historical trends in the U.S., we show that, while height and BMI show increasing genotypic penetrance over the course of 20(th) Century, education and heart disease show declining genotypic effects. Meanwhile, we find genotypic penetrance to be historically stable with respect to depression. Our findings help inform our understanding of how the genetic and environmental landscape of American society has changed over the past century, and have implications for research which models gene-environment (GxE) interactions, as well as polygenic score calculations in consortia studies that include multiple birth cohorts.