Genetic and epigenetic factors affecting carotid intima-media thickness in monozygotic twins

• EWAS using monozygotic twins detected 14 CpGs associated with IMT-Cmax and 21 CpGs associated with mean IMT. • GWAS using monozygotic twins detected seven SNPs associated with IMT-Cmax and one SNP associated with mean IMT. • Identified genetic and epigenetic factors were related to genes involved in metabolic mechanisms, thrombotic formation, and leukocyte dynamics. The intima-media thickness (IMT) of the carotid artery, an indicator of subclinical atherosclerosis, varies in close association with various factors such as diabetes and immune response. The extent of changes in IMT varies among individuals owing to both genetic and epigenetic factors. In this study, we aimed to identify single nucleotide polymorphisms (SNPs) and DNA methylation patterns that affect carotid IMT in monozygotic (MZ) twins. We measured the maximum IMT (IMT-Cmax) and the mean IMT in the common carotid artery wall using ultrasonography in 107 pairs of MZ twins recruited from the Osaka University Twin Registry. The genotyping of SNPs and the measurement of methylation levels were performed using a beads array, and the expression of each gene was determined by RNA sequencing. Linear regression analysis was performed on each of the two groups: one group consisted of twins randomly selected from each pair, and the other group consisted of co-twins. We identified a CpG site (cg02432467) on HS3ST6 as a significant epigenetic factor in both IMT-Cmax and mean IMT analyses. The methylation level at another site (cg07927379) was negatively correlated with LINC01006 expression and IMT-Cmax. Furthermore, there were significant differences in AP2A2 expression and mean IMT among individuals with each genotype of the rs10902263 polymorphism. We identified genetic and epigenetic factors associated with carotid IMT that may be useful for individualized assessments.