Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test

Juan Manuel Peralta, Marcio Almeida, Lawrence J. Abraham, Eric Moses, John Blangero

Research output: Chapter in Book/Conference paperConference paper

1 Citation (Scopus)
634 Downloads (Pure)

Abstract

We present a novel approach to detect potential cis-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 potential cis-regulatory effects, that surpassed the Bonferroni significance threshold, for ten transcripts. Stepwise removal of the cis-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-specific cis-regulation for four transcripts using both kernels, and our results agree with previous research that suggests the involvement of specific cis-located variants in the regulation of their neighboring gene.

Original languageEnglish
Title of host publicationBMC Proceedings
EditorsC.M.T. Greenwood, J.W. MacCluer, L. Almasy
Place of PublicationLondon
PublisherBioMed Central
Volume10
EditionS7
DOIs
Publication statusPublished - 2016
EventGenetic Analysis Workshop 19: Sequence, Blood Pressure and Expression Data - Vienna, Austria, Vienna, Austria
Duration: 24 Aug 201426 Aug 2014
Conference number: 19

Conference

ConferenceGenetic Analysis Workshop 19
CountryAustria
CityVienna
Period24/08/1426/08/14

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