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

Romain Charmet, Seamus Duffy, Sareh Keshavarzi, Beata Gyorgy, Michel Marre, Peter Rossing, Amy McKnight, Alexander Maxwell, Tarun veer Singh Ahluwalia, Andrew D. Paterson, David-Alexandre Trégouët, Samy Hadjadj

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Abstract

Objectives: To identify low frequency and common genetic variations associated with coronary artery disease (CAD) in populations of individuals with Type 1 Diabetes (T1D)
Methods and Results: A two stage genome wide association study (GWAS) was conducted. The discovery phase involved the meta-analysis of three GWAS cohorts totaling 434 patients with T1D and CAD (cases) and 3,123 T1D individuals with no evidence of CAD (controls). Replication of the top association signals (p <10-5) was performed in five additional independent cohorts totaling 595 cases and 2,612 controls. No single nucleotide polymorphism (SNP) reached the genome wide threshold of 5 x 10-8 for statistical significance. Nevertheless, three SNPs provided suggestive evidence for association with CAD in the combined studies: CDK18 rs138760780 (OR = 2.55 95% confidence interval [1.72 - 3.79], p = 3.04 10-6), PKD1 rs116092985 (OR = 1.53 [1.27 - 1.84], p = 9.67 10-6) and FAM189A2 rs12344245 (OR = 1.84 [1.41 - 2.41], p = 9.46 10-6). In addition, our analyses suggested that genetic variations at the ANKS1A, COL4A2 and APOE loci previously found associated with CAD in the general population could have significant effects in patients with T1D. 
 Conclusion: This study suggests three novel candidate genes for CAD in the subgroup of patients affected with T1D. The detected associations deserve to be definitively validated in additional epidemiological studies.
Original languageEnglish
Pages (from-to)1-10
JournalCardiovascular diabetology
DOIs
Publication statusPublished - 26 Apr 2018

Keywords

  • Type 1 diabetes
  • Genome-Wide Association Study
  • coronary artery disease

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