In silico genome-wide identification of m6A-associated SNPs as potential functional variants for periodontitis

Abstract

Genetic variation is considered to affect the N⁶ -methyladenosine (m6A) RNA transcript modification, which is the most prevalent posttranscriptional messenger RNA modification. This study aimed to identify m6A-associated single-nucleotide polymorphisms (m6A-SNPs) that may affect m6A methylation from numerous periodontitis (PD) SNPs. We identified an abundance of m6A-SNPs by analyzing raw data of published PD genome-wide association studies and m6A-SNPs list from the m6AVar database. Other evidence was found in public databases for expression quantitative trait loci (eQTL) and differential gene expression analysis. Accordingly, 1938 m6A-SNPs were identified, 104 of which appeared to be associated with PD (p < .05) while 65 showed eQTL signals. Lastly, the leading SNP rs2723183 (p = 3.93E-07) was predicted to regulate local gene IL-37 expression in PD (p = 2.64E-05; in GSE10334) and change regulatory motif RXRA. In summary, dozens of PD-associated m6A-SNPs were identified and their possible functions were demonstrated in this study.

Keywords: genome-wide association study; m6A; periodontitis; single-nucleotide polymorphism.