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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Chen, L; Ge, B; Casale, FP; Vasquez, L; Kwan, T; Garrido-Martín, D; Watt, S; ... Soranzo, N; + view all (2016) Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell , 167 (5) 1398-1414.e24. 10.1016/j.cell.2016.10.026. Green open access

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Abstract

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.

Type: Article
Title: Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cell.2016.10.026
Publisher version: http://doi.org/10.1016/j.cell.2016.10.026
Language: English
Additional information: © 2016 The Authors. Published by Elsevier Inc. This is an open access article under the Creative Commons Attribution 4.0 International (CC BY 4.0) license (http://creativecommons.org/licenses/by/4.0/)
Keywords: DNA methylation, EWAS, QTL, allele specific, histone modification, immune, monocyte, neutrophil, t-cell, transription
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: http://discovery.ucl.ac.uk/id/eprint/1530105
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