Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites.
Top associated SNPs in prostate cancer are significantly enriched in cis-expression quantitative trait loci and at transcription factor binding sites.
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前列腺癌中最相关的 SNP 在顺式表达数量性状位点和转录因子结合位点显着富集。
DOI：
10.18632/oncotarget.2179
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发表时间：
2014-08-15
期刊：
影响因子：
--
通讯作者：
Zhao Z
中科院分区：
文献类型：
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作者：
Jiang J;Jia P;Shen B;Zhao Z
虽然全基因组关联研究（GWAS）已经揭示了数千种疾病风险单核苷酸多态性（SNP），但它们的功能在很大程度上仍然未知。最近的研究表明GWAS风险变异在几种常见疾病中的调节作用;然而，前列腺癌中复杂的调节结构尚不清楚。我们研究了两个前列腺癌GWAS数据集中风险变异的潜在调控作用，通过它们与三个群体中的表达数量性状位点（eQTL）和/或转录因子结合位点（TFBS）的相互作用。我们的研究结果表明，中度相关的GWAS SNP在高加索人（CEU）中显著富集了cis-eQTL和TFBS，但在非洲裔美国人（AA）或日本人（JPT）中没有;这也在GWAS目录中的独立泛癌症相关SNP中观察到。我们发现CEU群体中eQTL的富集对来自CEU淋巴母细胞系的eQTL具有组织特异性。重要的是，我们通过将cis-eQTL和TFBS的结果重叠应用于CEU数据，确定了两个SNP，rs 2861405和rs 4766642。这些结果表明，前列腺癌相关的SNPs和泛癌相关的SNPs可能在CEU中发挥调节作用。然而，负富集导致AA或JPT，潜在的机制仍有待于在其他样品中阐明。
While genome-wide association studies (GWAS) have revealed thousands of disease risk single nucleotide polymorphisms (SNPs), their functions remain largely unknown. Recent studies have suggested the regulatory roles of GWAS risk variants in several common diseases; however, the complex regulatory structure in prostate cancer is unclear. We investigated the potential regulatory roles of risk variants in two prostate cancer GWAS datasets by their interactions with expression quantitative trait loci (eQTL) and/or transcription factor binding sites (TFBSs) in three populations. Our results indicated that the moderately associated GWAS SNPs were significantly enriched with cis-eQTLs and TFBSs in Caucasians (CEU), but not in African Americans (AA) or Japanese (JPT); this was also observed in an independent pan-cancer related SNPs from the GWAS Catalog. We found that the eQTL enrichment in the CEU population was tissue-specific to eQTLs from CEU lymphoblastoid cell lines. Importantly, we pinpointed two SNPs, rs2861405 and rs4766642, by overlapping results from cis-eQTL and TFBS as applied to the CEU data. These results suggested that prostate cancer associated SNPs and pan-cancer associated SNPs are likely to play regulatory roles in CEU. However, the negative enrichment results in AA or JPT and the potential mechanisms remain to be elucidated in additional samples.