An xQTL map integrates the genetic architecture of the human brain's transcriptome and epigenome.

An xQTL map integrates the genetic architecture of the human brain's transcriptome and epigenome.
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XQTL图整合了人脑的转录组和表观基因组的遗传结构。

DOI:
10.1038/nn.4632
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发表时间:
2017-10
影响因子:
25
通讯作者:
De Jager PL
De Jager PL
中科院分区:
医学1区
文献类型:
--
作者:
Ng B;White CC;Klein HU;Sieberts SK;McCabe C;Patrick E;Xu J;Yu L;Gaiteri C;Bennett DA;Mostafavi S;De Jager PL

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我们报告了一种新颖的多组学资源,该资源是通过对来自 411 名老年人背外侧前额皮质的 RNA 序列、DNA 甲基化和组蛋白乙酰化数据应用数量性状位点 (xQTL) 分析而生成的,这些数据具有所有三种数据类型。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。其中许多 SNP 影响多种分子特征,我们证明 SNP 对 RNA 表达的影响完全由这些位点中 9% 的表观遗传特征介导。此外,我们通过使用新资源 xQTL Serve 来优先考虑受 xQTL 影响最大的细胞类型,从而说明了它的实用性。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 (GWAS),并识别出 18 种新的精神分裂症和 2 种新的双相易感性变异,这是使用更大的基于血液的 eQTL 资源可以发现的基因座数量的两倍多。
We report a novel 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 adult individuals that 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 re-analyze published genome wide association studies (GWAS) using a 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 eQTL resource.
DOI: 10.1038/nature10405
发表时间: 2011-09-11
期刊: NATURE
影响因子: 64.8
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