The role of family factors in the association between early adulthood BMI and risk of cardiovascular disease. An intergenerational study of BMI in early adulthood and cardiovascular mortality in parents, aunts and uncles

BACKGROUND: High body mass index (BMI) in childhood and adolescence is related to cardiovascular disease (CVD). Causality is not established because common genetic or early life socioeconomic factors (family factors) may explain this relationship. We aimed to study the role of family factors in the association between BMI and CVD by investigating if early adulthood BMI in conscripts and CVD mortality in their parents/aunts/uncles are related. METHODS: Data from the Armed Forces Personnel Database (including height and weight among conscripts) were linked with data from the Norwegian Population Registry, generational data from the Norwegian Family Based Life Course Study, the National Educational Registry and the Cause of Death Registry using unique personal identification numbers. The study sample (N=369 464) was Norwegian males born 1967-1993, who could be linked to both parents and at least one maternal and one paternal aunt or uncle. Subsamples were identified as conscripts whose parents/aunts/uncles had data on cardiovascular risk factors available from Norwegian health surveys. Cox proportional hazards regression models were used to estimate hazard ratios (HR) of CVD mortality in the parental generation according to BMI categories of conscripts. RESULTS: Parents of conscripts with obesity or overweight had a higher hazard of CVD death (fathers HR obese: 1.99 (1.79,2.21), overweight: 1.33 (1.24,1.42) mothers HR obese: 1.65 (1.32,2.07), overweight: 1.23 (1.07,1.42)) than parents of normal- or underweight conscripts. Aunts and uncles of conscripts with obesity and overweight had an elevated hazard of CVD death, but less so than parents. Adjustment for CVD risk factors attenuated the results in parents, aunts and uncles. CONCLUSIONS: Family factors may impact the relationship between early adulthood overweight and CVD in parents. These can be genes with impact on BMI over generations and genes with a pleiotropic effect on both obesity and CVD, as well as shared environment over generations.