Genetic Predisposition to Type 2 Diabetes and Risk of Subclinical Atherosclerosis and Cardiovascular Diseases Among 160,000 Chinese adults.
Gan W., Bragg F., Walters RG., Millwood IY., Lin K., Chen Y., Guo Y., Vaucher J., Bian Z., Bennett D., Lv J., Yu C., Mahajan A., Clarke RJ., Li L., Holmes MV., McCarthy MI., Chen Z., China Kadoorie Biobank Collaborative Group (members listed in the online supplemental materials) None.
In observational studies, type 2 diabetes is associated with 2- to 4-fold higher risks of cardiovascular diseases (CVD). Using data from the China Kadoorie Biobank, we examined associations of genetically-predicted type 2 diabetes with CVD among ∼160,000 participants, to assess whether these relationships are causal. A type 2 diabetes genetic risk score (comprising 48 established risk variants) was associated with the presence of carotid plaque (OR 1.17 [95% CI 1.05, 1.29] per 1 unit higher log-odds of type 2 diabetes; n=6,819), and elevated risk of ischaemic stroke (IS) (1.08 [1.02, 1.14]; n=17,097), non-lacunar IS (1.09 [1.03, 1.16]; n=13,924) and major coronary event (1.12 [1.02, 1.23]; n= 5,081). There was no significant association with lacunar IS (1.03 [0.91, 1.16], n=3,173) or intracerebral haemorrhage (ICH) (1.01 [0.94, 1.10], n=6,973), although effect estimates were imprecise. These associations were consistent with observational associations of type 2 diabetes with CVD in CKB (p for heterogeneity>0.3), and with the associations of type 2 diabetes with IS, ICH and coronary heart disease in two-sample Mendelian randomisation analyses based on summary statistics from European population GWAS (p for heterogeneity>0.2). In conclusion, among Chinese adults, genetic predisposition to type 2 diabetes was associated with atherosclerotic CVD, consistent with a causal association.