Tobacco and type 2 diabetes: is the association explained by genetic factors?

Background: Smoking and use of Swedish smokeless tobacco (snus) are associated with increased risk of type 2 diabetes (T2D). Our aim was to estimate the unique and shared genetic components of these traits and to what extent the association is explained by shared genetic factors.

Methods: We used twins of the Swedish Twin Registry who responded to a questionnaire between 1998 and 2006 (n = 40 247) and were followed until 2015 in the National Prescription and Patient Registries. We estimated hazard ratios (HRs) and odds ratios (ORs) for the association between smoking/snus use and T2D (n = 2130) and used structural equation models to estimate genetic and environmental variance components and genetic correlations.

Results: Current smokers [HR 1.69, 95% confidence interval (CI), 1.49-1.92] and snus users (HR 1.19, 95% CI 1.01-1.41) had an increased risk of T2D. In within-pair analyses of monozygotic twins, corresponding ORs were 1.36, 95% CI 0.75-2.46 (smoking) and 1.54, 95% CI 0.80-2.99 (snus). Heritability was 43% (95% CI 36-51) for ever smoking, 58% (95% CI 44- 70) for ever snus use and 66% (95% CI 59-72) for T2D. The genetic correlation with T2D was 18% (95% CI 1-35) for smoking and -6% (95% CI -24 to 4) for snus use, indicating that only a small fraction of the genetic influence is shared.

Conclusions: We could confirm that consumers of snus and cigarettes are at increased risk of T2D. Both snus use and smoking have strong genetic components, which appears to be attributable primarily to genes that are distinct from those promoting T2D.