Abundant contribution of STRs to gene expression variability in humans

Considering the topic of gene-environment interactions, quantitative human traits include phenotypes such as “toxicity to a given environmental toxicant”, “drug-independent adverse drug reactions” (diADRs), and “drug efficacy”.

The contribution of repetitive elements to quantitative human traits is largely unknown. Authors [reference below] report 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. Their survey identified 2,060 significant expression STRs (eSTRs). These eSTRs were replicable in orthogonal populations and expression assays.

They used variance partitioning to disentangle the contribution of eSTRs from that of linked single-nucleotide variants (SNVs) and insertion/deletions (indels) and found that eSTRs contribute 10–15% of the cis heritability mediated by all common variants. Further functional genomic analyses showed that eSTRs are enriched in conserved regions, eSTRs co-localize with regulatory elements, and they 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, authors 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.

 Nat Genet Jan 2o16; 48: 22–29

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