Cell
Volume 167, Issue 5, 17 November 2016, Pages 1398-1414.e24
Journal home page for Cell

Resource
Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

https://doi.org/10.1016/j.cell.2016.10.026Get rights and content
Under a Creative Commons license
open access

Highlights

  • Genome, transcriptome, and epigenome reference panel in three human immune cell types

  • Identified 4,418 genes associated with epigenetic changes independent of genetics

  • Described genome-epigenome coordination defining cell-type-specific regulatory events

  • Functionally mapped disease mechanisms at 345 unique autoimmune disease loci

Summary

Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14+ monocytes, CD16+ neutrophils, and naive CD4+ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of cis-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.

Keywords

immune
monocyte
neutrophil
t-cell
EWAS
histone modification
DNA methylation
transription
allele specific
QTL

Cited by (0)

28

Co-first author

29

Lead Contact