Abundant Contribution of Short Tandem Repeats to Gene Expression Variation in Humans

• NCJ Number: 249961
• Journal: Nature Genetics Volume: 48 Issue: 1 Dated: January 2016 Pages: 22-29
• Author(s): M. Gymrek; T. Willems; A. Guilmatre; H. Y. Zeng; B. Markus; S. Georgiev; M. J. Daly; A. L. Price; J. K. Pritchard; A. J. Sharp; Y. Erlich
• Date Published: January 2016
• Length: 8 pages
• Grant Number(s): 2014-DN-BX-K089
• Agencies: NIJ-Sponsored
• Publication Type: Research (Applied/Empirical)
• Award: Robust STR calling from High-throughput Sequencing Technologies

Annotation

Since the contribution of repetitive elements to quantitative human traits is largely unknown, this article reports on a genome-wide survey of the contribution of short tandem repeats (STRs), which constitute one of the most polymorphic and abundant repeat classes, to gene expression in humans.

Abstract

The survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays. Variance partitioning was used to disentangle the contribution of eSTRs from that of linked SNPs and indels and found that eSTRs contribute 10-15 percent of the cis heritability mediated by all common variants. Further functional genomic analyses showed that eSTRs are enriched in conserved regions, colocalize with regulatory elements, and may modulate certain histone modifications. By analyzing known genome-wide association study (GWAS) signals and searching for new associations in 1,685 whole genomes from deeply phenotyped individuals, the study found that eSTRs are enriched in various clinically relevant conditions. These results highlight the contribution of STRs to the genetic architecture of quantitative human traits. 17 figures and 78 references (Publisher abstract modified)