Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Chen, Lu; Garrido Martín, Diego, 1992-; Guigó Serra, Roderic; Soranzo, Nicole

doi:http://dx.doi.org/10.1016/j.cell.2016.10.026

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

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Chen L, Ge B, Paolo Casale F, Vasquez L, Kwan T, Garrido-Martín D et al. Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell. 2016;167(5):1398-414. DOI: 10.1016/j.cell.2016.10.026

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.