High-Resolution Mapping of Expression-QTLs Yields Insight into Human Gene Regulation

TLDR

Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). The study aims to generate a high‑resolution map of cis‑regulatory eQTL locations using a novel Bayesian hierarchical model. The authors reanalyzed HapMap lymphoblastoid cell line data with a Bayesian hierarchical model to map cis‑eQTLs. They found strong enrichment of cis‑eQTLs within 250 bp upstream of the transcription end site and around the transcription start site, with most eQTLs located inside or near genes (only 5 % more than 20 kb upstream), exonic SNPs twice as likely as intronic ones, and evidence that mRNA stability plays a key role in steady‑state mRNA levels.

Abstract

Recent studies of the HapMap lymphoblastoid cell lines have identified large numbers of quantitative trait loci for gene expression (eQTLs). Reanalyzing these data using a novel Bayesian hierarchical model, we were able to create a surprisingly high-resolution map of the typical locations of sites that affect mRNA levels in cis. Strikingly, we found a strong enrichment of eQTLs in the 250 bp just upstream of the transcription end site (TES), in addition to an enrichment around the transcription start site (TSS). Most eQTLs lie either within genes or close to genes; for example, we estimate that only 5% of eQTLs lie more than 20 kb upstream of the TSS. After controlling for position effects, SNPs in exons are ∼2-fold more likely than SNPs in introns to be eQTLs. Our results suggest an important role for mRNA stability in determining steady-state mRNA levels, and highlight the potential of eQTL mapping as a high-resolution tool for studying the determinants of gene regulation.