Abundant contribution of short tandem repeats to gene expression variation in humans.
Nat Genet
; 48(1): 22-9, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26642241
ABSTRACT
The contribution of repetitive elements to quantitative human traits is largely unknown. Here we 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. 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 that of linked SNPs and 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, colocalize with regulatory elements and 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, we 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Expressão Gênica
/
Genoma Humano
/
Repetições de Microssatélites
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article