Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL, USA.
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.
Science. 2020 Sep 11;369(6509). doi: 10.1126/science.aba3066.
Many complex human phenotypes exhibit sex-differentiated characteristics. However, the molecular mechanisms underlying these differences remain largely unknown. We generated a catalog of sex differences in gene expression and in the genetic regulation of gene expression across 44 human tissue sources surveyed by the Genotype-Tissue Expression project (GTEx, v8 release). We demonstrate that sex influences gene expression levels and cellular composition of tissue samples across the human body. A total of 37% of all genes exhibit sex-biased expression in at least one tissue. We identify cis expression quantitative trait loci (eQTLs) with sex-differentiated effects and characterize their cellular origin. By integrating sex-biased eQTLs with genome-wide association study data, we identify 58 gene-trait associations that are driven by genetic regulation of gene expression in a single sex. These findings provide an extensive characterization of sex differences in the human transcriptome and its genetic regulation.
许多复杂的人类表型表现出性别差异的特征。然而，这些差异背后的分子机制在很大程度上仍然未知。我们生成了一个目录，其中包含了 44 个人体组织来源的基因表达和基因表达遗传调控的性别差异，这些组织来源是通过基因型-组织表达项目（GTEx，v8 版本）调查的。我们证明，性会影响全身组织样本的基因表达水平和细胞组成。在至少一种组织中，总共有 37%的基因表现出性别偏倚表达。我们确定了具有性别差异效应的顺式表达数量性状基因座（eQTLs），并描述了它们的细胞起源。通过将性别偏倚的 eQTL 与全基因组关联研究数据相结合，我们确定了 58 个基因-性状关联，这些关联是由单个性别对基因表达的遗传调控所驱动的。这些发现为人类转录组及其遗传调控中的性别差异提供了广泛的特征描述。
