Structural variants (SVs) are an important source of human genome diversity, but their functional effects are poorly understood. We mapped 61,668 SVs in 613 individuals from the GTEx project and measured their effects on gene expression. We estimate that common SVs are causal at 2.66% of eQTLs, a 10.5-fold enrichment relative to their abundance in the genome. Duplications and deletions were the most impactful variant types, whereas the contribution of mobile element insertions was small (0.12% of eQTLs, 1.9-fold enriched). Multitissue analysis of eQTLs revealed that gene-altering SVs show more constitutive effects than other variant types, with 62.09% of coding SV-eQTLs active in all tissues with eQTL activity compared with 23.08% of coding SNV- and indel-eQTLs. Noncoding SVs, SNVs and indels show broadly similar patterns. We also identified 539 rare SVs associated with nearby gene expression outliers. Of these, 62.34% are noncoding SVs that affect gene expression but have modest enrichment at regulatory elements, showing that rare noncoding SVs are a major source of gene expression differences but remain difficult to predict from current annotations. Both common and rare SVs often affect the expression of multiple genes: SV-eQTLs affect an average of 1.82 nearby genes, whereas SNV- and indel-eQTLs affect an average of 1.09 genes, and 21.34% of rare expression-altering SVs show effects on two to nine different genes. We also observe significant effects on rare gene expression changes extending 1 Mb from the SV. This provides a mechanism by which individual SVs may have strong or pleiotropic effects on phenotypic variation.

中文翻译：

---

结构变异是人类基因表达差异的主要来源，通常影响多个附近的基因

结构变异（SV）是人类基因组多样性的重要来源，但对其功能影响却知之甚少。我们绘制了 GTEx 项目中 613 名个体的 61,668 个 SV，并测量了它们对基因表达的影响。我们估计常见的 SV 与 eQTL 的 2.66% 存在因果关系，相对于它们在基因组中的丰度而言，富集了 10.5 倍。重复和缺失是最有影响力的变异类型，而移动元件插入的贡献很小（eQTL 的 0.12%，富集了 1.9 倍）。eQTL 的多组织分析表明，基因改变的 SV 比其他变异类型表现出更多的组成效应，其中 62.09% 的编码 SV-eQTL 在所有具有 eQTL 活性的组织中都具有活性，而编码 SNV 和 indel-eQTL 的这一比例为 23.08%。非编码 SV、SNV 和插入缺失显示出大致相似的模式。我们还鉴定了 539 个与附近基因表达异常值相关的罕见 SV。其中，62.34% 是影响基因表达的非编码 SV，但在调控元件上有适度的富集，这表明罕见的非编码 SV 是基因表达差异的主要来源，但仍然难以从当前的注释中预测。常见和罕见的 SV 常常影响多个基因的表达：SV-eQTL 平均影响 1.82 个附近基因，而 SNV-和 indel-eQTL 平均影响 1.09 个基因，21.34% 的罕见表达改变 SV 表现出影响两到九个不同的基因。我们还观察到对从 SV 延伸 1 Mb 的罕见基因表达变化有显着影响。这提供了一种机制，通过该机制，个体 SV 可以对表型变异产生强烈或多效性影响。