Instrumental variable analysis using offspring BMI in childhood as an indicator of parental BMI in relation to mortality.

Childhood BMI shows associations with adult mortality, but these may be influenced by effects of ill health in childhood on BMI and later mortality. To avoid this, we used offspring childhood BMI as an instrumental variable (IV) for own BMI in relation to mortality and compared it with conventional associations of own childhood BMI and own mortality. We included 36,097 parent-offspring pairs with measured heights and weights from the Copenhagen School Health Records Register and register-based information on death. Hazard ratios (HR) were estimated using adjusted Cox regression models. For all-cause mortality, per zBMI at age 7 the conventional HR = 1.07 (95%CI: 1.04-1.09) in women and 1.02 (95%CI: 0.92-1.14) in men, whereas the IV HR = 1.23 (95%CI: 1.15-1.32) in women and 1.05 (95%CI: 0.94-1.17) in men. Per zBMI at age 13, the conventional HR = 1.11 (95%CI: 1.08-1.15) in women and 1.03 (95%CI: 0.99-1.06) in men, whereas the IV HR = 1.30 (95%CI: 1.19-1.42) in women and 1.15 (95%CI: 1.04-1.29) in men. Only conventional models showed indications of J-shaped associations. Our IV analyses suggest that there is a causal relationship between BMI and mortality that is positive at both high and low BMI values.