The overdue promise of short tandem repeat variation for heritability

Trends Genet. 2014 Nov;30(11):504-12. doi: 10.1016/j.tig.2014.07.008. Epub 2014 Aug 30.


Short tandem repeat (STR) variation has been proposed as a major explanatory factor in the heritability of complex traits in humans and model organisms. However, we still struggle to incorporate STR variation into genotype-phenotype maps. We review here the promise of STRs in contributing to complex trait heritability and highlight the challenges that STRs pose due to their repetitive nature. We argue that STR variants are more likely than single-nucleotide variants to have epistatic interactions, reiterate the need for targeted assays to genotype STRs accurately, and call for more appropriate statistical methods in detecting STR-phenotype associations. Lastly, we suggest that somatic STR variation within individuals may serve as a read-out of disease susceptibility, and is thus potentially a valuable covariate for future association studies.

Keywords: epistasis; heritability; microsatellites; sequencing technologies; short tandem repeats.

Publication types

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

MeSH terms

  • Animals
  • Genetic Association Studies / methods*
  • Genetic Association Studies / trends
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation*
  • Genome-Wide Association Study / methods
  • Genome-Wide Association Study / trends
  • Genotype
  • Humans
  • Microsatellite Repeats / genetics*
  • Mutation Rate
  • Phenotype