RT Journal Article
SR Electronic
T1 Abundant contribution of short tandem repeats to gene expression variation in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 017459
DO 10.1101/017459
A1 Melissa Gymrek
A1 Thomas Willems
A1 Haoyang Zeng
A1 Barak Markus
A1 Mark J. Daly
A1 Alkes L. Price
A1 Jonathan Pritchard
A1 Yaniv Erlich
YR 2015
UL http://biorxiv.org/content/early/2015/04/02/017459.abstract
AB Expression quantitative trait loci (eQTLs) are a key tool to dissect cellular processes mediating complex diseases. However, little is known about the role of repetitive elements as eQTLs. 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. Functional genomic analyses showed that eSTRs are enriched in conserved regions, co-localize with regulatory elements, and are predicted to modulate histone modifications. Our results show that eSTRs provide a novel set of regulatory variants and highlight the contribution of repeats to the genetic architecture of quantitative human traits.