BACKGROUND Gene regulation is important for cells and tissues to function. It has been studied from two aspects at the genomic level, the identification of expression quantitative trait loci (eQTLs) and identification of long-range chromatin interactions. It is important to understand their relationship, such as whether eQTLs regulate their target genes through physical chromatin interaction. Although chromatin interactions have been widely believed to be one of the main mechanisms underlying eQTLs, most evidence came from studies of cell lines and yet no direct evidence exists for tissues. RESULTS We performed various joint analyses of eQTL and high-throughput chromatin conformation capture (Hi-C) data from 11 human primary tissue types and 2 human cell lines. We found that chromatin interaction frequency is positively associated with the number of genes that have eQTLs and that eQTLs and their target genes tend to fall into the same topologically associating domain (TAD). These results are consistent across all tissues and cell lines we evaluated. Moreover, in 6 out of 11 tissues (aorta, dorsolateral prefrontal cortex, hippocampus, pancreas, small bowel, and spleen), tissue-specific eQTLs are significantly enriched in tissue-specific frequently interacting regions (FIREs). CONCLUSIONS Our data have demonstrated the close spatial proximity between eQTLs and their target genes among multiple human primary tissues.

中文翻译：

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对多组织Hi-C和eQTL数据的联合分析表明，eQTL及其靶基因之间的空间接近性很高。

背景技术基因调节对于细胞和组织的功能很重要。从基因组水平的两个方面进行了研究，即表达定量性状基因座（eQTL）的鉴定和长距离染色质相互作用的鉴定。重要的是要了解它们之间的关系，例如eQTL是否通过物理染色质相互作用调节其靶基因。尽管人们普遍认为染色质相互作用是eQTL的主要机制之一，但大多数证据来自细胞系研究，但尚无直接的组织证据。结果我们对来自11种人类原代组织类型和2种人类细胞系的eQTL和高通量染色质构象捕获（Hi-C）数据进行了各种联合分析。我们发现染色质相互作用频率与具有eQTL的基因数量呈正相关，并且eQTL及其目标基因倾向于落入相同的拓扑关联域（TAD）。这些结果在我们评估的所有组织和细胞系中都是一致的。此外，在11种组织（主动脉，背外侧前额叶皮层，海马，胰腺，小肠和脾脏）中，有6种组织特异性eQTL在组织特异性频繁相互作用区域（FIREs）中明显富集。结论我们的数据证明了eQTL及其靶基因在多个人类原发组织之间的紧密空间邻近性。这些结果在我们评估的所有组织和细胞系中都是一致的。此外，在11种组织（主动脉，背外侧前额叶皮层，海马，胰腺，小肠和脾脏）中，有6种组织特异性eQTL在组织特异性频繁相互作用区域（FIREs）中明显富集。结论我们的数据证明了eQTL及其靶基因在多个人类原发组织之间的紧密空间邻近性。这些结果在我们评估的所有组织和细胞系中都是一致的。此外，在11种组织（主动脉，背外侧前额叶皮层，海马，胰腺，小肠和脾脏）中，有6种组织特异性eQTL在组织特异性频繁相互作用区域（FIREs）中明显富集。结论我们的数据证明了eQTL及其靶基因在多个人类原发组织之间的紧密空间邻近性。