TCF7L2 and type 2 diabetes mellitus: For example, we have shown above that BMI had a risk effect on T2D, which has been confirmed by RCT35, that T2D had a significant reverse effect on BMI and effect size was negative, and that there was a SNP (at the TCF7L2 gene locus) that appeared to have pleiotropic effects on T2D and BMI (Fig. 3), a mixture model of causality, reverse causality and pleiotropy.