The impact of short tandem repeat variation on gene expression

Nat Genet. 2019 Nov;51(11):1652-1659. doi: 10.1038/s41588-019-0521-9. Epub 2019 Nov 1.


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 provide insights into putative mechanisms. Here, we leverage whole-genome sequencing and expression data for 17 tissues from the Genotype-Tissue Expression Project to identify more than 28,000 STRs for which repeat number is associated with expression of nearby genes (eSTRs). We use fine-mapping to quantify the probability that each eSTR is causal and characterize the top 1,400 fine-mapped eSTRs. We identify hundreds of eSTRs linked with published genome-wide association study signals and implicate specific eSTRs in complex traits, including height, schizophrenia, inflammatory bowel disease and intelligence. Overall, our results support the hypothesis that eSTRs contribute to a range of human phenotypes, and our data should serve as a valuable resource for future studies of complex traits.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Body Height / genetics
  • Computational Biology
  • Gene Expression Regulation*
  • Genome, Human*
  • Genome-Wide Association Study*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Intelligence / genetics
  • Microsatellite Repeats / genetics*
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci*
  • Schizophrenia / genetics