Body Mass Index and Mortality Is the Association Explained by Genetic Factors?

Background: Numerous studies have shown that higher body mass index (BMI) is associated with higher mortality. We investigated the extent to which this association might be explained by genetic factors. Methods: We used data from the Swedish Twin Registry on twins born 1886-1958 who answered a questionnaire in 1969/1970 or 1972 (n = 44,258). Information on mortality from all-causes (n = 14,217), cardiovascular disease (CVD; n = 9009), and coronary heart disease (CHD; n = 3564) was obtained by linkage to the national Causes of Death Registry for the years 1972-2004. The association between BMI and mortality was studied without control for genetic factors in cohort analyses and with control for genetic factors in co-twin control analyses. Results: In cohort analyses, there was a clear dose-response relationship between BMI and mortality. Hazard ratios per 1 unit increase in BMI in subjects with BMI >= 18.5 were 1.05 (95% confidence interval = 1.05-1.06) for all-cause mortality, 1.07 (1.07-1.09) for CVD mortality, and 1.09 (1.08-1.10) for CHD mortality. Similar results were seen in co-twin control analyses of dizygotic twins. However, within monozygotic twins, BMI was associated with death from CHD (OR = 1.06; 1.00-1.12), whereas the association with all-cause mortality (1.01, 0.98-1.04) and CVD mortality (1.02, 0.98-1.06) was weak. Conclusions: Our findings indicate that there is an association between high BMI and mortality from CHD that is not explained by genetic confounding. However, a large part of the association between BMI and other causes of death may be explained by genes rather than by a causal link between these factors.