Impact of common regulatory single-nucleotide variants on gene expression profiles in whole blood
Impact of common regulatory single-nucleotide variants on gene expression profiles in whole blood
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DOI：
10.1038/ejhg.2012.106
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发表时间：
2013-01-01
影响因子：
5.2
通讯作者：
Prokisch, Holger
中科院分区：
文献类型：
--
作者：
Mehta, Divya;Heim, Katharina;Prokisch, Holger
全基因组关联研究（GWASs）已经发现了大量复杂性状的易感基因座。GWAS鉴定的候选基因的功能解释和因果变异的可靠分配仍然是一个重大挑战。表达数量性状（eQTL）定位促进了数量性状的风险位点的识别，并可能允许GWAS候选基因的优先级。eQTL研究的一个主要挑战是需要更大的样本数量和重复。本研究的目的是评估人类全血eQTL的稳健性和可重复性，并测试其在鉴定复杂性状病因学中涉及的推定功能变体中的价值。在本研究中，我们从全血中进行了综合eQTL定位。发现样本包括来自一般人群样本（KORA F3）的322名高加索人。经过严格的Bonferroni校正后，共检测到363个顺式和8个反式eQTL。其中，98.6%和50%的顺式和反式eQTL分别可以在两个独立的群体（KORA F4（n = 740）和SHIP-TREND（n = 653））中复制。此外，我们发现了以前报道的与疾病基因座（n = 59）或数量性状基因座（n = 20）相关的SNPs的调节变异的证据，表明这些eSNPs可能的功能机制。我们的数据表明，全血中的eQTL在研究中是高度稳健和可重复的，并强调了全血eQTL定位在人类GWAS候选基因优先级排序中的相关性。European Journal of Human Genetics（2013）21，48-54; doi：10.1038/ejhg.2012.106; 2012年6月13日在线发表
Genome-wide association studies (GWASs) have uncovered susceptibility loci for a large number of complex traits. Functional interpretation of candidate genes identified by GWAS and confident assignment of the causal variant still remains a major challenge. Expression quantitative trait (eQTL) mapping has facilitated identification of risk loci for quantitative traits and might allow prioritization of GWAS candidate genes. One major challenge of eQTL studies is the need for larger sample numbers and replication. The aim of this study was to evaluate the robustness and reproducibility of whole-blood eQTLs in humans and test their value in the identification of putative functional variants involved in the etiology of complex traits. In the current study, we performed comphrehensive eQTL mapping from whole blood. The discovery sample included 322 Caucasians from a general population sample (KORA F3). We identified 363 cis and 8 trans eQTLs after stringent Bonferroni correction for multiple testing. Of these, 98.6% and 50% of cis and trans eQTLs, respectively, could be replicated in two independent populations (KORA F4 (n = 740) and SHIP-TREND (n = 653)). Furthermore, we identified evidence of regulatory variation for SNPs previously reported to be associated with disease loci (n = 59) or quantitative trait loci (n = 20), indicating a possible functional mechanism for these eSNPs. Our data demonstrate that eQTLs in whole blood are highly robust and reproducible across studies and highlight the relevance of whole-blood eQTL mapping in prioritization of GWAS candidate genes in humans. European Journal of Human Genetics (2013) 21, 48-54; doi: 10.1038/ejhg.2012.106; published online 13 June 2012