Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test. Issue 7 (October 2016)

• Record Type: Journal Article
• Authors: Peralta, Juan; Almeida, Marcio; Abraham, Lawrence; Moses, Eric; Blangero, John
• Is Part Of: BMC proceedings. Volume 10:Issue 7(2016)
• Page Start: 103
• Page End: 108
• Publication Date: 2016-10
• Subjects: Medicine -- Congresses; Biology -- Congresses; 610.5
• DOI: 10.1186/s12919-016-0013-1
• Languages: English
• ISSNs: 1753-6561

Abstract

Abstract We present a novel approach to detect potentialcis -acting regulatory loci that combines the functional potential, an empirical DNase-seq based estimate of the allele-specificity of DNase-I hypersensitivity sites, with kernel-based variance component association analyses against expression phenotypes. To test our method we used public ENCODE whole genome DNase-I sequencing data, from a single sample, to estimate the functional potentials of the subset of 10, 552 noncoding heterozygous single-nucleotide polymorphisms (SNPs) that were also present in the Genetic Analysis Workshop 19 (GAW19) family-based data set. We then built two covariance kernels, one nonweighted and one weighted by the functional potentials, and conducted kernel-based variance component association analyses against the 20, 527 transcript expression phenotypes in the GAW19 family-based data set. We found signals of potentialcis -regulatory effects, that surpassed the Bonferroni significance threshold, for ten transcripts. Stepwise removal of thecis -located SNPs from the weighted kernel lead to the disappearance of the association signal from our top transcript hit. We found compelling evidence of allele-specificcis -regulation for four transcripts using both kernels, and our results agree with previous research that suggests the involvement of specificcis -located variants in the regulation of their neighboring gene.