GSE31388
Variation in chromatin accessibility is a key determinant of heritable variation in gene expression
While it is well established that variation in gene expression levels can be influenced by single nucleotide polymorphisms (SNPs), little is known about the regulatory mechanisms by which this occurs. To address this gap, we used DNaseI sequencing to measure genome-wide chromatin accessibility in 70 Yoruba lymphoblastoid cell lines (LCLs), for which genome-wide genotypes and estimates of gene expression levels based on RNA-sequencing are also available. We obtained a total of 2.8 billion uniquely mapped DNase-seq reads, which allowed us to produce genome-wide maps of chromatin accessibility for each individual. We identified 7,759 locations at which DNase-seq read depth correlates significantly with variation at a nearby SNP or indel (FDR=10%). We call such variants ''chromatin accessibility Quantitative Trait Loci'' (or caQTLs). Most caQTLs lie within or very near the target DNaseI hypersensitive sites, and they are strongly enriched within inferred transcription factor binding sites. We find that a substantial fraction (14%) of caQTLs are also significantly associated with variation in the expression levels of nearby genes (namely, these loci are also classified as eQTLs), suggesting that changes in chromatin accessibility or transcription factor binding frequently lead to gene expression changes. Conversely, 12% of eQTL SNPs are also classified as caQTLs and, accounting for incomplete power, we estimate that the true fraction may be as high as 41%. Our observations indicate that caQTLs are abundant in the human genome, and are likely to be significant contributors to phenotypic variation. Overall design: DNaseI-Seq on 70 YRI Hapmap cell lines. Each individual sequenced on several lanes of a flow cell on the Illumina Genome Analyzer II