Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.cell.2016.10.026

Type

Journal article

Journal

Cell

Volume

167

Pages

1398 - 1414.e24

Keywords

DNA methylation, EWAS, QTL, allele specific, histone modification, immune, monocyte, neutrophil, t-cell, transription, Adult, Aged, Alternative Splicing, Epigenomics, Female, Genetic Predisposition to Disease, Hematopoietic Stem Cells, Histone Code, Humans, Immune System Diseases, Male, Middle Aged, Monocytes, Neutrophils, Quantitative Trait Loci, T-Lymphocytes, Transcription, Genetic, Young Adult