Co-occurring expression and methylation QTLs allow detection of common causal variants and shared biological mechanisms

Inherited genetic variation affects local gene expression and DNA methylation in humans. Most expression quantitative trait loci (cis-eQTLs) occur at the same genomic location as methylation QTLs (cis-meQTLs), suggesting a common causal variant and shared mechanism. Using DNA and RNA from peripheral blood of Bangladeshi individuals, here we use co-localization methods to identify eQTL-meQTL pairs likely to share a causal variant. We use partial correlation and mediation analyses to identify >400 of these pairs showing evidence of a causal relationship between expression and methylation (i.e., shared mechanism) with many additional pairs we are underpowered to detect. These co-localized pairs are enriched for SNPs showing opposite associations with expression and methylation, although a many SNPs affect multiple CpGs in opposite directions. This work demonstrates the pervasiveness of co-regulated expression and methylation in the human genome. Applying this approach to other type...遗传性基因变异可影响人类的局部基因表达与DNA甲基化（DNA methylation）。多数顺式表达数量性状位点（cis-eQTLs）与顺式甲基化数量性状位点（cis-meQTLs）位于同一基因组区域，提示二者存在共同的因果变异与共享调控机制。本研究利用孟加拉国个体外周血中的DNA与RNA，通过共定位分析方法筛选出大概率共享因果变异的eQTL-meQTL关联对。我们通过偏相关分析与中介分析，在上述关联对中鉴定出400余对存在基因表达与DNA甲基化间因果关联（即共享调控机制）的位点；另有大量关联对因统计效力不足而未能检出。这些共定位关联对富集于那些与基因表达和DNA甲基化呈现反向关联的单核苷酸多态性（single nucleotide polymorphisms，SNPs）位点，尽管诸多SNPs可对多个CpG位点产生反向调控作用。本研究证实了人类基因组中基因表达与DNA甲基化共调控现象的普遍性。将此分析方法应用于其他类型……