Genetic variation, gene expression and DNA methylation influence each other in a complex way. To study the impact of sequence variation and DNA methylation on gene expression, we generated geno5mC, a database that contains statistically significant SNP-CpG associations that are biologically classified either through co-localization with known regulatory regions (promoters and enhancers), or through known correlations with the expression levels of nearby genes.

The SNP rs727563 can be used to illustrate the usefulness of this approach. This SNP has been associated with inflammatory bowel disease through GWAS, but it is not located near any gene related to this phenotype. However, geno5mC reveals that rs727563 is associated with the methylation state of several CpGs located in promoter regions of genes reported to be involved in inflammatory processes. This case exemplifies how geno5mC can be used to infer relevant and previously unknown interactions between described disease-associated SNPs and their functional targets.

遗传变异、基因表达和 DNA 甲基化以复杂的方式相互影响。为了研究序列变异和 DNA 甲基化对基因表达的影响，我们生成了 geno5mC，该数据库包含具有统计学意义的 SNP-CpG 关联，这些关联通过与已知调控区（启动子和增强子）的共定位或通过已知的与附近基因表达水平的相关性。

SNP rs727563 可用于说明此方法的有用性。该 SNP 通过 GWAS 与炎症性肠病相关，但它不位于与该表型相关的任何基因附近。然而，geno5mC 揭示 rs727563 与位于据报道参与炎症过程的基因启动子区域中的几个 CpG 的甲基化状态相关。该案例举例说明了如何使用 geno5mC 来推断所描述的疾病相关 SNP 与其功能目标之间的相关和以前未知的相互作用。