| Literature DB >> 26300125 |
Fabian Grubert1, Judith B Zaugg2, Maya Kasowski1, Oana Ursu1, Damek V Spacek1, Alicia R Martin1, Peyton Greenside3, Rohith Srivas1, Doug H Phanstiel1, Aleksandra Pekowska4, Nastaran Heidari1, Ghia Euskirchen1, Wolfgang Huber4, Jonathan K Pritchard5, Carlos D Bustamante1, Lars M Steinmetz2, Anshul Kundaje6, Michael Snyder7.
Abstract
Deciphering the impact of genetic variants on gene regulation is fundamental to understanding human disease. Although gene regulation often involves long-range interactions, it is unknown to what extent non-coding genetic variants influence distal molecular phenotypes. Here, we integrate chromatin profiling for three histone marks in lymphoblastoid cell lines (LCLs) from 75 sequenced individuals with LCL-specific Hi-C and ChIA-PET-based chromatin contact maps to uncover one of the largest collections of local and distal histone quantitative trait loci (hQTLs). Distal QTLs are enriched within topologically associated domains and exhibit largely concordant variation of chromatin state coordinated by proximal and distal non-coding genetic variants. Histone QTLs are enriched for common variants associated with autoimmune diseases and enable identification of putative target genes of disease-associated variants from genome-wide association studies. These analyses provide insights into how genetic variation can affect human disease phenotypes by coordinated changes in chromatin at interacting regulatory elements.Entities:
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Year: 2015 PMID： 26300125 PMCID： PMC4556133 DOI： 10.1016/j.cell.2015.07.048
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582