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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