Properties of structural variants and short tandem repeats associated with gene expression and complex traits

David Jakubosky(University of California San Diego), Matteo D’Antonio(University of California San Diego), Marc Jan Bonder(European Bioinformatics Institute), Craig Smail(Stanford University), Margaret K. R. Donovan(University of California San Diego), William W. Greenwald(University of California San Diego), Hiroko Matsui(University of California San Diego), Marc Jan Bonder(European Bioinformatics Institute), Na Cai(European Bioinformatics Institute), Ivan Carcamo‐Orive(Cardiovascular Institute of the South), Matteo D’Antonio(University of California San Diego), Kelly A. Frazer(University of California San Diego), William W. Greenwald(University of California San Diego), David Jakubosky(University of California San Diego), Joshua W. Knowles(Cardiovascular Institute of the South), Hiroko Matsui(University of California San Diego), Davis J. McCarthy(European Bioinformatics Institute), Bogdan Mirăuță(European Bioinformatics Institute), Stephen B. Montgomery(Stanford University), Thomas Quertermous(Cardiovascular Institute of the South), Daniel D. Seaton(European Bioinformatics Institute), Craig Smail(Stanford University), Erin N. Smith(University of California San Diego), Oliver Stegle(European Bioinformatics Institute), Agnieszka D’Antonio‐Chronowska(University of California San Diego), Oliver Stegle(European Bioinformatics Institute), Erin N. Smith(University of California San Diego), Stephen B. Montgomery(Stanford University), Christopher DeBoever(University of California San Diego), Kelly A. Frazer(University of California San Diego)
Nature Communications
June 10, 2020
10.1038/s41467-020-16482-4
Cited by 136Open Access
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Abstract

Structural variants (SVs) and short tandem repeats (STRs) comprise a broad group of diverse DNA variants which vastly differ in their sizes and distributions across the genome. Here, we identify genomic features of SV classes and STRs that are associated with gene expression and complex traits, including their locations relative to eGenes, likelihood of being associated with multiple eGenes, associated eGene types (e.g., coding, noncoding, level of evolutionary constraint), effect sizes, linkage disequilibrium with tagging single nucleotide variants used in GWAS, and likelihood of being associated with GWAS traits. We identify a set of high-impact SVs/STRs associated with the expression of three or more eGenes via chromatin loops and show that they are highly enriched for being associated with GWAS traits. Our study provides insights into the genomic properties of structural variant classes and short tandem repeats that are associated with gene expression and human traits.

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