title: Finding potential cis-regulatory loci using allele-specific chromatin accessibility as weights in a kernel-based variance component test.
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.
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas at the Rio Grande Valley, One West University Blvd., Brownsville, TX 78520 USA.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Peralta
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas at the Rio Grande Valley, One West University Blvd., Brownsville, TX 78520 USA.
authors.forename: Marcio
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Abraham
authors.affiliation: Centre for Genetic Origins of Health and Disease, University of Western Australia, 35 Stirling Hwy, Crawley, WA 6009 Australia.
authors.forename: Eric
authors.initials: E
authors.lastname: Moses
authors.affiliation: South Texas Diabetes and Obesity Institute, University of Texas at the Rio Grande Valley, One West University Blvd., Brownsville, TX 78520 USA ; South Texas Diabetes and Obesity Institute, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229 USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero