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Free keywords:
Adult
Aged
Alternative Splicing
*Epigenomics
Female
Genetic Predisposition to Disease
Hematopoietic Stem Cells/metabolism
Histone Code
Humans
Immune System Diseases/*genetics
Male
Middle Aged
Monocytes/*metabolism
Neutrophils/*metabolism
Quantitative Trait Loci
T-Lymphocytes/*metabolism
*Transcription, Genetic
Young Adult
*DNA methylation
*Ewas
*Qtl
*allele specific
*histone modification
*immune
*monocyte
*neutrophil
*t-cell
*transription
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.
