Enhancer histone-QTLs are enriched on autoimmune risk haplotypes and influence gene expression within chromatin networks.

ABSTRACT: Genetic variants can confer risk to complex genetic diseases by modulating gene expression through changes to the epigenome. To assess the degree to which genetic variants influence epigenome activity, we integrate epigenetic and genotypic data from lupus patient lymphoblastoid cell lines to identify variants that induce allelic imbalance in the magnitude of histone post-translational modifications, referred to herein as histone quantitative trait loci (hQTLs). We demonstrate that enhancer hQTLs are enriched on autoimmune disease risk haplotypes and disproportionately influence gene expression variability compared with non-hQTL variants in strong linkage disequilibrium. We show that the epigenome regulates HLA class II genes differently in individuals who carry HLA-DR3 or HLA-DR15 haplotyp

SUBMITTER: Pelikan RC 

PROVIDER: S-EPMC6060153 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature