Toggle Main Menu Toggle Search

Open Access padlockePrints

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Lookup NU author(s): Dr Daniel Rico RodriguezORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


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.

Publication metadata

Author(s): Chen L, Ge B, Casale FP, Vasquez L, Kwan T, Garrido-Martin D, Watt S, Yan Y, Kundu K, Ecker S, Datta A, Richardson D, Burden F, Mead D, Mann AL, Fernandez JM, Rowlston S, Wilder SP, Farrow S, Shao XJ, Lambourne JJ, Redensek A, Albers CA, Amstislavskiy V, Ashford S, Berentsen K, Bomba L, Bourque G, Bujold D, Busche S, Caron M, Chen SH, Cheung W, Delaneau O, Dermitzakis ET, Elding H, Colgiu I, Bagger FO, Flicek P, Habibi E, Iotchkova V, Janssen-Megens E, Kim B, Lehrach H, Lowy E, Mandoli A, Matarese F, Maurano MT, Morris JA, Pancaldi V, Pourfarzad F, Rehnstrom K, Rendon A, Risch T, Sharifi N, Simon MM, Sultan M, Valencia A, Walter K, Wang SY, Frontini M, Antonarakis SE, Clarke L, Yaspo ML, Beck S, Guigo R, Rico D, Martens JHA, Ouwehand WH, Kuijpers TW, Paul DS, Stunnenberg HG, Stegle O, Downes K, Pastinen T, Soranzo N

Publication type: Article

Publication status: Published

Journal: Cell

Year: 2016

Volume: 167

Issue: 5

Pages: 1398-1414

Print publication date: 17/11/2016

Online publication date: 17/11/2016

Acceptance date: 14/10/2016

Date deposited: 22/02/2017

ISSN (print): 0092-8674

ISSN (electronic): 1097-4172

Publisher: Cell Press


DOI: 10.1016/j.cell.2016.10.026


Altmetrics provided by Altmetric


Funder referenceFunder name
Canada Research Chair
European Molecular Biology Laboratory
FEBS long-term fellowship
Max Planck Society
National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre
National Institute for Health Research Cambridge Biomedical Research Centre
UK National Institute for Health Research Cambridge Biomedical Research Centre
"la Caixa"-Severo Ochoa pre-doctoral fellowship
Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research
FEDER "Una Manera de hacer Europa"
Genome Canada
La Caixa
National Institute for Health Research (NIHR)
NHS Health Education England
EP1-120608Canadian Institutes of Health Research (CIHR)
EP1-120608Genome Quebec (CIHR)
HEALTH-F5-2011-282510EU FP7 High Impact Project BLUEPRINT
G0800270UK Medical Research Council
PT13/0001/0021Spanish National Bioinformatics Institute (INB-ISCIII)
SEV-2012-0208Spanish Ministry of Economy and Competitiveness, "Centro de Excelencia Severo Ochoa"
WT098051Wellcome Trust
RE/13/6/30180BHF Cambridge Centre of Excellence
SP/09/002British Heart Foundation
WT091310Wellcome Trust