Abstract
Short tandem repeats (STRs) have been implicated in a variety of complex traits in humans. However, genome-wide studies of the effects of STRs on gene expression thus far have had limited power to detect associations and elucidate the underlying biological mechanisms. Here, we leverage whole genome sequencing and expression data for 17 tissues from GTEx to identify STRs whose repeat lengths are associated with expression of nearby genes (eSTRs). Our analysis reveals more than 3,000 high-confidence eSTRs, which are enriched in known or predicted regulatory regions. We show eSTRs may act through a variety of mechanisms. We further identify hundreds of eSTRs that potentially drive published GWAS signals and implicate specific eSTRs in height and schizophrenia. Overall, our results demonstrate that eSTRs potentially contribute to a range of human phenotypes. We expect that our comprehensive eSTR catalog will serve as a valuable resource for future studies of complex traits.
