RTN4 and FBXL17 Genes are Associated with Coronary Heart Disease in Genome-Wide Association Analysis of Lithuanian Families

Abstract

Coronary heart disease (CHD) is a complex and heterogeneous cardiovascular disease. There are many genome-wide association studies (GWAS) performed worldwide to extract the causative genetic factors. Moreover, each population may have some exceptional genetic characteristic. Thus, the background of our study is from the previous Lithuanian studies (the LiVicordia Project), which demonstrated the differences of the atherosclerosis process between Lithuanian and Swedish male individuals. In this study we performed GWAS of 32 families of Lithuanian origin in search of significant candidate genetic markers [single nucleotide polymorphisms (SNPs)] of CHD in this population. After careful clinical and biochemical phenotype evaluation, the ∼770K SNPs genotyping (Illumina HumanOmniExpress-12 v1.0 array) and familial GWAS analyses were performed. Twelve SNPs were found to be significantly associated with the CHD phenotype (p value <0.0001; the power >0.65). The odds ratio (OR) values were calculated. Two SNPs (rs17046570 in the RTN4 gene and rs11743737 in the FBXL17 gene) stood out and may prove to be important genetic factors for CHD risk. Our results correspond with the findings in other studies, and these two SNPs may be the susceptibility loci for CHD.

Keywords: Atherosclerosis; Coronary heart disease (CHD); Genome-wide association study(ies) (GWAS); Transmission disequilibrium test (TDT).

Figure 1.

Manhattan plot. Single nucleotide polymorphism distribution with logarithmic transformation of the p value. The horizontal line depicts the selected significance level (α = 0.0001). The x axis represents the SNPs’ positions according to each chromosome, the y axis shows −log10(P) values of the SNPs.