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

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.

Association of the Anxiogenic and Alerting Effects of Caffeine with ADORA2A and ADORA1 Polymorphisms and Habitual Level of Caffeine Consumption

“…Both rs2298383 and rs3761422 are located in potential promoter regions upstream of several newly identified variants of ADORA2A exon 1 (Yu et al, 2004) near the corresponding transcription start sites. SNPs located within or immediately around these sites have been highlighted as having high potential to alter gene function (Veyrieras et al, 2008). In contrast to ADORA2A SNPs, no association of caffeineinduced anxiety was found with ADORA1 SNPs.…”

RNA-Seq and human complex diseases: recent accomplishments and future perspectives

“…80 RNA-Seq studies, and our recent work among them, 43 revealed that many genes annotated in currently available databases (ie, RefSeq, UCSC and Ensembl) have extended 3' UTRs, containing putative affecting donor and acceptor splice sites (GU and AG) altering the splicing of the coding exons. In detail, in (1) a canonically spliced pre-mRNA following the GU-AG rule; (2) an example of nucleotide variation/s occurring within the introns and generating a novel acceptor 'cryptic' splice site.…”

ATP2C2andDYX1C1are putative modulators of dyslexia‐related MMR

“…To identify eQTL effects, eQTL databases were analyzed (Borel et al., 2011; Dimas et al., 2009; Dixon et al., 2007; Fehrmann et al., 2011; Greenawalt et al., 2011; Grundberg et al., 2009; GTEx Consortium, 2015; Kim, Cho, Lee, & Webster, 2012; Kirsten et al., 2015; Mehta et al., 2013; Myers et al., 2007; Ramasamy et al., 2014; Schadt et al., 2008; Schröder et al., 2011; Veyrieras et al., 2008; Westra et al., 2013; Xia et al., 2012; Zeller et al., 2010). We only considered SNPs identified in brain or blood tissue and eQTLs had to be replicated in at least one study.…”