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Cell. 2015 Aug 27;162(5):1051-65. doi: 10.1016/j.cell.2015.07.048. Epub 2015 Aug 20.

Genetic Control of Chromatin States in Humans Involves Local and Distal Chromosomal Interactions.

Author information

  • 1Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • 3Biomedical Informatics Graduate Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 4The European Molecular Biology Laboratory Heidelberg, 69117 Heidelberg, Germany.
  • 5Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • 6Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Computer Science, Stanford University, Stanford, CA 94305, USA.
  • 7Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: mpsnyder@stanford.edu.

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.

Copyright © 2015 Elsevier Inc. All rights reserved.

PMID:
26300125
[PubMed - indexed for MEDLINE]
PMCID:
PMC4556133
[Available on 2016-08-27]
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