Epigenetics is a reversible molecular mechanism that plays a critical role in many developmental, adaptive, and disease processes. DNA methylation has been shown to regulate gene expression and the advent of high throughput technologies has made genome-wide DNA methylation analysis possible. We investigated the effect of DNA methylation in eQTL mapping (methylation-adjusted eQTLs), by incorporating DNA methylation as a SNP-based covariate in eQTL mapping in African American derived hepatocytes. We found that the addition of DNA methylation uncovered new eQTLs and eGenes. Previously discovered eQTLs were significantly altered by the addition of DNA methylation data suggesting that methylation may modulate the association of SNPs to gene expression. We found that methylation-adjusted eQTLs which were less significant compared to PC-adjusted eQTLs were enriched in lipoprotein measurements (FDR = 0.0040), immune system disorders (FDR = 0.0042), and liver enzyme measurements (FDR = 0.047), suggesting a role of DNA methylation in regulating the genetic basis of these phenotypes. Our methylation-adjusted eQTL analysis also uncovered novel SNP-gene pairs. For example, our study found the SNP, rs11546996, was associated to PNKP. In a previous GWAS, this SNP was associated with primary biliary cirrhosis although the causal gene was thought to be SPIB. Our methylation-adjusted method potentially adds new understanding to the genetic basis of complex diseases that disproportionally affect African Americans.

中文翻译：

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在非裔美国人中将DNA甲基化纳入eQTL作图。

表观遗传学是一种可逆的分子机制，在许多发育，适应和疾病过程中起着至关重要的作用。DNA甲基化已被证明可以调节基因表达，并且高通量技术的出现使全基因组DNA甲基化分析成为可能。我们通过将DNA甲基化作为基于SNP的协变量纳入非洲裔美国人来源的肝细胞的eQTL映射中，研究了DNA甲基化在eQTL映射（甲基化调整的eQTL）中的作用。我们发现，DNA甲基化的添加揭示了新的eQTL和eGenes。通过添加DNA甲基化数据，以前发现的eQTL发生了显着变化，这表明甲基化可能会调节SNP与基因表达的关联。我们发现，与PC调整后的eQTL相比，甲基化调整后的eQTL的重要性较低，脂蛋白测量值（FDR = 0.0040），免疫系统异常（FDR = 0.0042）和肝酶测量值（FDR = 0.047）丰富，表明了这一作用DNA甲基化调节这些表型的遗传基础。我们的甲基化调整后的eQTL分析还发现了新的SNP基因对。例如，我们的研究发现SNP rs11546996与PNKP相关。在先前的GWAS中，尽管该SNP与原发性胆汁性肝硬化有关，但因果基因被认为是SPIB。我们经过甲基化调整的方法可能会为复杂影响非裔美国人的复杂疾病的遗传基础增加新的理解。和肝酶的测定（FDR = 0.047），表明DNA甲基化在调节这些表型的遗传基础中的作用。我们的甲基化调整后的eQTL分析还发现了新的SNP基因对。例如，我们的研究发现SNP rs11546996与PNKP相关。在先前的GWAS中，该SNP与原发性胆汁性肝硬化有关，尽管其因果基因被认为是SPIB。我们经过甲基化调整的方法可能会为复杂影响非裔美国人的复杂疾病的遗传基础增加新的理解。和肝酶的测定（FDR = 0.047），表明DNA甲基化在调节这些表型的遗传基础中的作用。我们的甲基化调整后的eQTL分析还发现了新的SNP基因对。例如，我们的研究发现SNP rs11546996与PNKP相关。在先前的GWAS中，尽管该SNP与原发性胆汁性肝硬化有关，但因果基因被认为是SPIB。我们经过甲基化调整的方法可能会为复杂影响非裔美国人的复杂疾病的遗传基础增加新的理解。在先前的GWAS中，尽管该SNP与原发性胆汁性肝硬化有关，但因果基因被认为是SPIB。我们经过甲基化调整的方法可能会为复杂影响非裔美国人的复杂疾病的遗传基础增加新的理解。在先前的GWAS中，尽管该SNP与原发性胆汁性肝硬化有关，但因果基因被认为是SPIB。我们经过甲基化调整的方法可能会为复杂影响非裔美国人的复杂疾病的遗传基础增加新的理解。