Heavy inheritance: Genetic pathways from excess weight to biological aging and health in old age

In this paper, we investigate the impact of excess body weight on biological aging and health in old age. Drawing on a large sample of U.S. adults from the Health and Retirement Study, we construct a frailty index, defined as the proportion of age-related health deficits present in a person. Our findings reveal a positive association between BMI (and other indicators of excess weight) and the frailty index. To identify a causal relationship, we use a polygenic risk score (PRS) for BMI as an instrumental variable for excess weight. We further demonstrate that the effect of the PRS on BMI strengthens with later birth years, indicating that, for given age, younger cohorts have experienced longer exposure to obesogenic environments. This trend allows us to construct a gene-environment instrument for excess weight. Our results show a significant, substantial, and nearly log-linear effect of excess weight on health in old age: on average, each additional unit increase in BMI leads to a 4 to 5 percent rise in the frailty index.