Jan 17, 2019

Fine-mapping cis -regulatory variants in diverse human populations

ELife
Ashley TehranchiHunter B Fraser

Abstract

Genome-wide association studies (GWAS) are a powerful approach for connecting genotype to phenotype. Most GWAS hits are located in cis-regulatory regions, but the underlying causal variants and their molecular mechanisms remain unknown. To better understand human cis-regulatory variation, we mapped quantitative trait loci for chromatin accessibility (caQTLs)-a key step in cis-regulation-in 1000 individuals from 10 diverse populations. Most caQTLs were shared across populations, allowing us to leverage the genetic diversity to fine-map candidate causal regulatory variants, several thousand of which have been previously implicated in GWAS. In addition, many caQTLs that affect the expression of distal genes also alter the landscape of long-range chromosomal interactions, suggesting a mechanism for long-range expression QTLs. In sum, our results show that molecular QTL mapping integrated across diverse populations provides a high-resolution view of how worldwide human genetic variation affects chromatin accessibility, gene expression, and phenotype. This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that minor is...Continue Reading

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Mentioned in this Paper

Genome-Wide Association Study
Quantitative Trait Loci
Regulation of Biological Process
Gene Expression
Evaluation
Genes, Regulator
Distal Muscle
Drug Interactions
Gene Regulatory Networks
Mapping, Vessel

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