Pharmacogenomics and Personalized Medicine (Oct 2021)
Exploring the Epigenetic Regulatory Role of m6A-Associated SNPs in Type 2 Diabetes Pathogenesis
Abstract
Miao Chen,1,2 Weimin Lin,1 Jianru Yi,1,2 Zhihe Zhao1,2 1State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 2Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Jianru Yi; Zhihe Zhao Tel +86-28-85503040; +86-28-85503645Email [email protected]; [email protected]: Genetic factors in type 2 diabetes (T2D) pathogenesis have been widely explored by the genome-wide association studies (GWAS), identifying a great amount of susceptibility loci. With the development of high-resolution sequencing, the N(6)-methyladenosine (m6A) RNA modification has been proved to be affected by genetic variation. In this study, we identified the T2D-associated m6A-SNPs from T2D GWAS data and explored the underlying mechanism of the pathogenesis of T2D.Methods: We examined the association of m6A-SNPs with T2D among large-scale T2D GWAS summary statistics and further performed multi-omics integrated analysis to explore the potential role of the identified m6A-SNPs in T2D pathogenesis.Results: Among the 15,124 T2D-associated m6A-SNPs, 71 of them reach the genome-wide significant threshold (5.0e-05). The leading SNP rs4993986 (C>G), which is located near the m6A modification site at the 3ʹ end of the HLA-DQB1 transcript, is expected to participate in the pathogenesis of T2D by influencing m6A modification to regulate the HLA-DQB1 expression.Conclusion: The current study has suggested a potential correlation between m6A-SNPs and T2D pathogenesis and also provided new insights into the pathogenic mechanism of the T2D susceptibility loci identified by GWAS.Keywords: type 2 diabetes, single nucleotide polymorphism, epigenetics, m6A, genome-wide association study
