Chen Miao, Lin Weimin, Yi Jianru, Zhao Zhihe
State 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.
Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, People's Republic of China.
Pharmgenomics Pers Med. 2021 Oct 27;14:1369-1378. doi: 10.2147/PGPM.S334346. eCollection 2021.
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.
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.
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 3' end of the transcript, is expected to participate in the pathogenesis of T2D by influencing m6A modification to regulate the expression.
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.
全基因组关联研究（GWAS）已广泛探索2型糖尿病（T2D）发病机制中的遗传因素，识别出大量易感位点。随着高分辨率测序技术的发展，N(6)-甲基腺苷（m6A）RNA修饰已被证明受遗传变异影响。在本研究中，我们从T2D的GWAS数据中识别出与T2D相关的m6A单核苷酸多态性（SNP），并探索T2D发病机制的潜在机制。
我们在大规模T2D的GWAS汇总统计数据中检测m6A-SNP与T2D的关联，并进一步进行多组学综合分析，以探索所识别的m6A-SNP在T2D发病机制中的潜在作用。
在15,124个与T2D相关的m6A-SNP中，有71个达到全基因组显著性阈值（5.0e-05）。领先的SNP rs4993986（C>G）位于转录本3'端的m6A修饰位点附近，预计通过影响m6A修饰来调节表达，从而参与T2D的发病机制。
当前研究表明m6A-SNP与T2D发病机制之间存在潜在关联，也为GWAS识别出的T2D易感位点的致病机制提供了新见解。
