We report a multi-omic resource generated by applying quantitative trait locus (xQTL) analyses to RNA sequence, DNA methylation and histone acetylation data from the dorsolateral prefrontal cortex of 411 older adults who have all three data types. We identify SNPs significantly associated with gene expression, DNA methylation and histone modification levels. Many of these SNPs influence multiple molecular features, and we demonstrate that SNP effects on RNA expression are fully mediated by epigenetic features in 9% of these loci. Further, we illustrate the utility of our new resource, xQTL Serve, by using it to prioritize the cell type(s) most affected by an xQTL. We also reanalyze published genome wide association studies using an xQTL-weighted analysis approach and identify 18 new schizophrenia and 2 new bipolar susceptibility variants, which is more than double the number of loci that can be discovered with a larger blood-based expression eQTL resource.

中文翻译：

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xQTL 图整合了人脑转录组和表观基因组的遗传结构。

我们报告了通过对 RNA 序列、DNA 甲基化和组蛋白乙酰化数据应用数量性状基因座 (xQTL) 分析生成的多组学资源，这些数据来自 411 名具有所有三种数据类型的老年人的背外侧前额叶皮层。我们确定了与基因表达、DNA 甲基化和组蛋白修饰水平显着相关的 SNP。许多这些 SNP 影响多个分子特征，我们证明 SNP 对 RNA 表达的影响完全由 9% 这些位点的表观遗传特征介导。此外，我们通过使用它来确定受 xQTL 影响最大的细胞类型的优先级，从而说明我们的新资源 xQTL Serve 的效用。我们还使用 xQTL 加权分析方法重新分析已发表的全基因组关联研究，并确定了 18 种新的精神分裂症和 2 种新的双相易感性变异，