Introduction: Genome-wide association studies have identified approximately 1000 lipid-associated loci, but functional variants are less known. Materials & methods: The authors identified RNA modification-related single-nucleotide polymorphisms (RNAm-SNPs) in summary data from a genome-wide association study. By applying Mendelian randomization analysis, the authors identified gene expression levels involved in the regulation of RNAm-SNPs on low-density lipoprotein cholesterol (LDL-C) levels. Results: The authors identified 391 RNAm-SNPs that were significantly associated with LDL-C levels. RNAm-SNPs in NPC1L1, LDLR, APOB, MYLIP, LDLRAP1 and ABCA6 were identified. The RNAm-SNPs were associated with gene expression. The expression levels of 112 genes were associated with LDL-C levels, and some of them (e.g., APOB, SMARCA4 and SH2B3) were associated with coronary artery disease. Conclusion: This study identified many RNAm-SNPs in LDL-C loci and elucidated the relationship among the SNPs, gene expression and LDL-C.

Keywords: RNA modification; gene expression; genome-wide association study; lipids.