%0 Journal Article %A Natsuhiko Kumasaka %A Andrew Knights %A Daniel Gaffney %T Fine-mapping cellular QTLs with RASQUAL and ATAC-seq %D 2015 %R 10.1101/018788 %J bioRxiv %P 018788 %X When cellular traits are measured using high-throughput DNA sequencing quantitative trait loci (QTLs) manifest at two levels: population level differences between individuals and allelic differences between cis-haplotypes within individuals. We present RASQUAL (Robust Allele Specific QUAntitation and quality controL), a novel statistical approach for association mapping that integrates genetic effects and robust modelling of biases in next generation sequencing (NGS) data within a single, probabilistic framework. RASQUAL substantially improves causal variant localisation and sensitivity of association detection over existing methods in RNA-seq, DNaseI-seq and ChIP-seq data. We illustrate how RASQUAL can be used to maximise association detection by generating the first map of chromatin accessibility QTLs (caQTLs) in a European population using ATAC-seq. Despite a modest sample size, we identified 2,706 independent caQTLs (FDR 10%) and illustrate how RASQUAL’s improved causal variant localisation provides powerful information for fine-mapping disease-associated variants. We also map “multipeak” caQTLs, identical genetic associations found across multiple, independent open chromatin regions and illustrate how genetic signals in ATAC-seq data can be used to link distal regulatory elements with gene promoters. Our results highlight how joint modelling of population and allele-specific genetic signals can improve functional interpretation of noncoding variation. %U https://www.biorxiv.org/content/biorxiv/early/2015/04/30/018788.full.pdf