Cell
Volume 162, Issue 5, 27 August 2015, Pages 1051-1065
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Article
Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions

https://doi.org/10.1016/j.cell.2015.07.048Get rights and content
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Highlights

  • Analyses of variations in histone marks reveal histone QTLs in regulatory elements

  • Physically interacting loci show genetically coordinated chromatin levels

  • Regulatory elements sharing hQTLs are enriched in topologically associated domains

  • hQTLs are enriched for GWAS SNPs and enable identification of putative target genes

Summary

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.

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