Novel risk genes identified in a genome-wide association study for coronary artery disease in patients with type 1 diabetes

Background Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identify low frequency and common genetic variations associated with coronary artery disease in populations of individuals with type 1 diabetes. Methods A two-stage genome wide association study was conducted. The discovery phase involved the meta-analysis of three genome-wide association cohorts totaling 434 patients with type 1 diabetes and coronary artery disease (cases) and 3123 T1D individuals with no evidence of coronary artery disease (controls). Replication of the top association signals (p < 10 −5 ) was performed in five additional independent cohorts totaling 585 cases and 2612 controls. Results One locus (rs115829748, located upstream of the MAP1B gene) reached the statistical threshold of 5 × 10 −8 for genome-wide significance but did not replicate. Nevertheless, three single nucleotide polymorphisms provided suggestive evidence for association with coronary artery disease in the combined studies: CDK18 rs138760780 (OR = 2.60 95% confidence interval [1.75–3.85], p = 2.02 × 10 −6 ), FAM189A2 rs12344245 (OR = 1.85 [1.41–2.43], p = 8.52 × 10 −6 ) and PKD1 rs116092985 (OR = 1.53 [1.27–1.85], p = 1.01 × 10 −5 ). In addition, our analyses suggested that genetic variations at the ANKS1A , COL4A2 and APOE loci previously found associated with coronary artery disease in the general population could have stronger effects in patients with type 1 diabetes. Conclusions This study suggests three novel candidate genes for coronary artery disease in the subgroup of patients affected with type 1 diabetes. The detected associations deserve to be definitively validated in additional epidemiological studies.