Genome-wide eQTLs and heritability for gene expression traits in unrelated individuals.
Genome-wide eQTLs and heritability for gene expression traits in unrelated individuals.
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DOI：
10.1186/1471-2164-15-13
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发表时间：
2014-01-09
期刊：
影响因子：
4.4
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Yang S;Liu Y;Jiang N;Chen J;Leach L;Luo Z;Wang M
虽然近年来在复杂性状的全基因组关联研究（GWAS）中明显存在的所谓“缺失遗传力”的潜在可能来源一直在积极探索，但解决这个谜团仍然是一项具有挑战性的任务。研究全基因组基因表达性状的遗传力有助于理解表型和基因型之间的关系。在这里，我们使用微阵列基因表达测量的淋巴母细胞系和全基因组SNP基因型数据从210个HapMap个人研究基因表达性状的遗传性。应用方差分量模型分析了10,720个基因的遗传力，检测到1,043个表达量QTL。我们的研究结果表明，基因表达性状的遗传力呈双峰分布，一个峰值接近0%，另一个峰值接近100%。这种基因表达遗传力的群体内变异模式在不同无关个体的HapMap群体中很常见，但与CEU和YRI三个样本中获得的结果不同。管家基因和顺式eQTL相关基因显示出更高的遗传力水平。顺式和反式eQTL对遗传力的累积贡献相当。最后，我们模拟了多个eQTL的基因的基因-基因相互作用（上位性），并揭示上位性并不是在所有基因中普遍存在，但在解释总遗传力的一些基因分析作出了重大贡献。我们利用混合效应模型分析来估计基于群体的样本的遗传成分。基于对4个HapMap群体全基因组基因表达的分析，我们展示了对不同群体表达性状遗传遗传力分布的详细利用，并强调了研究基因表达水平上的相互作用作为缺失遗传力变异的重要来源的重要性。本文的在线版本（doi：10.1186/1471-2164-15-13）包含补充材料，可供授权用户使用。
While the possible sources underlying the so-called ‘missing heritability’ evident in current genome-wide association studies (GWAS) of complex traits have been actively pursued in recent years, resolving this mystery remains a challenging task. Studying heritability of genome-wide gene expression traits can shed light on the goal of understanding the relationship between phenotype and genotype. Here we used microarray gene expression measurements of lymphoblastoid cell lines and genome-wide SNP genotype data from 210 HapMap individuals to examine the heritability of gene expression traits. Heritability levels for expression of 10,720 genes were estimated by applying variance component model analyses and 1,043 expression quantitative loci (eQTLs) were detected. Our results indicate that gene expression traits display a bimodal distribution of heritability, one peak close to 0% and the other summit approaching 100%. Such a pattern of the within-population variability of gene expression heritability is common among different HapMap populations of unrelated individuals but different from that obtained in the CEU and YRI trio samples. Higher heritability levels are shown by housekeeping genes and genes associated with cis eQTLs. Both cis and trans eQTLs make comparable cumulative contributions to the heritability. Finally, we modelled gene-gene interactions (epistasis) for genes with multiple eQTLs and revealed that epistasis was not prevailing in all genes but made a substantial contribution in explaining total heritability for some genes analysed. We utilised a mixed effect model analysis for estimating genetic components from population based samples. On basis of analyses of genome-wide gene expression from four HapMap populations, we demonstrated detailed exploitation of the distribution of genetic heritabilities for expression traits from different populations, and highlighted the importance of studying interaction at the gene expression level as an important source of variation underlying missing heritability. The online version of this article (doi:10.1186/1471-2164-15-13) contains supplementary material, which is available to authorized users.
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