Genome-wide association studies have identified many susceptible loci to explore the genetic factors of adiposity. However, the specific mechanisms by which these SNPs (single nucleotide polymorphism), particularly in the non-coding region, are involved in the pathogenesis of adiposity remain unclear. Recently, genetic variation is thought to affect N⁶-methyladenosine (m6A) RNA modification, which is the most common post-transcriptional messenger RNA modification. In this study, we identified a large number of BMI (body mass index)-associated m6A-SNPs from published GWAS summary statistics through a public database and explored their potential mechanisms involved in the pathogenesis of adiposity. In summary, the integrative analysis detected 20,993 BMI-associated m6A-SNPs and 230 m6A-SNPs which reached the genome-wide suggestive threshold (5.0E-05), while 215 of them showed eQTL signals and 167 are the corresponding genes. The leading SNP rs8024 (C/A) was located next to the m6A modification site of 3′UTR of the IPO9 gene, which was predicted to affect the m6A modification site and regulate the expression of the IPO9 gene to participate in the pathogenesis of adiposity. This m6A-SNP/gene expression/adiposity triplets provide a new annotation for the pathogenic mechanism of adiposity risk loci identified by GWAS.

全基因组关联研究已经确定了许多易感基因座，以探索肥胖的遗传因素。然而，这些SNP（单核苷酸多态性），特别是在非编码区，参与肥胖病发病机制的具体机制仍不清楚。最近，人们认为遗传变异会影响ñ⁶-甲基腺苷（m6A）RNA修饰，这是最常见的转录后信使RNA修饰。在这项研究中，我们通过公共数据库从已发布的GWAS汇总统计数据中识别了大量与BMI（体重指数）相关的m6A-SNP，并探讨了其与肥胖症发病机制有关的潜在机制。总之，综合分析检测到20,993个与BMI相关的m6A-SNP和230个m6A-SNPs达到了全基因组提示阈值（5.0E-05），而其中有215个显示eQTL信号，而167个显示了相应的基因。领先的SNP rs8024（C / A）位于IPO9基因3'UTR的m6A修饰位点附近，预计会影响m6A修饰位点并调节IPO9基因的表达以参与肥胖的发病机理。