BackgroundAccumulating evidence has shown that type 2 diabetes (T2D) and coronary artery disease (CAD) may stem from a ‘common soil’. The aim of our study was to examine the association between genetic predisposition to T2D and the risk of severe CAD among patients with acute coronary syndromes (ACS) undergoing angiography.MethodsThe current case–control study included 1414 ACS patients with at least one major epicardial vessel stenosis > 50% enrolled in the ACS Genetic Study. The severity of CAD was quantified by the number of coronary arteries involved. Genetic risk score (GRS) was calculated using 41 common variants that robustly associated with increased risk of T2D in East Asians. Logistic regression models were used to estimate the association between GRS and the severity of CAD.ResultsIn the age-, sex- and BMI-adjusted model, each additional risk allele was associated with a 6% increased risk of multi-vessel disease (OR = 1.06, 95% CI 1.02–1.09). The OR was 1.43 (95% CI 1.08–1.89) for the risk of severe CAD when comparing the extreme tertiles of T2D-GRS. The association was not reduced after further adjustment for conventional cardiovascular risk factors. Additional adjustment for T2D status in our regression model attenuated the association by approximately one quarter. In subgroup analysis, the strengths of the associations between GRS and the severity of CAD were broadly similar in terms of baseline demographic information and disease characteristics.ConclusionsOur data indicated that genetic predisposition to T2D is associated with elevated risk of severe CAD. This association revealed a possible causal relationship and is partially mediated through diabetic status.