Abundant contribution of short tandem repeats to gene expression variation in humans.
Abundant contribution of short tandem repeats to gene expression variation in humans.
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DOI：
10.1038/ng.3461
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发表时间：
2016-01
期刊：
影响因子：
30.8
通讯作者：
Erlich Y
中科院分区：
文献类型：
--
作者：
Gymrek M;Willems T;Guilmatre A;Zeng H;Markus B;Georgiev S;Daly MJ;Price AL;Pritchard JK;Sharp AJ;Erlich Y
重复元素对人类定量特征的贡献在很大程度上是未知的。在这里，我们报告了一项全基因组调查，研究短串联重复序列 (STR) 对人类基因表达的贡献，STR 是多态性最高、最丰富的重复序列之一。我们的调查确定了 2,060 个显着表达 STR (eSTR)。这些 eSTR 在正交群体和表达测定中是可复制的。我们使用方差划分将 eSTR 的贡献与相连的 SNP 和插入缺失分开，发现 eSTR 贡献了所有常见变异介导的顺式遗传力的 10%–15%。进一步的功能基因组分析表明，eSTR 在保守区域富集，与调控元件共定位，并且可以调节某些组蛋白修饰。通过分析已知的 GWAS 命中并在 1,685 个深度表型全基因组中寻找新的关联，我们发现 eSTR 在各种临床相关条件下丰富。这些结果强调了短串联重复对人类定量性状遗传结构的贡献。
The contribution of repetitive elements to quantitative human traits is largely unknown. Here, we report a genome-wide survey of the contribution of Short Tandem Repeats (STRs), one of the most polymorphic and abundant repeat classes, to gene expression in humans. Our survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays. We used variance partitioning to disentangle the contribution of eSTRs from linked SNPs and indels and found that eSTRs contribute 10%–15% of the cis-heritability mediated by all common variants. Further functional genomic analyses showed that eSTRs are enriched in conserved regions, co-localize with regulatory elements, and can modulate certain histone modifications. By analyzing known GWAS hits and searching for new associations in 1,685 deeply-phenotyped whole-genomes, we found that eSTRs are enriched in various clinically-relevant conditions. These results highlight the contribution of short tandem repeats to the genetic architecture of quantitative human traits.