Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
- 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.
- Consortium data used in this publication
- It's part of the BLUEPRINT epigenome project. The accession numbers for the alignment data reported in this paper are European Genome-phenome Archive (EGA): WGS: EGAD00001002663; RNA: EGAD00001002671/EGAD00001002674/EGAD00001002675; ChIP-seq: EGAD00001002670/EGAD00001002672/EGAD00001002673; and 450K DNA methylation: EGAS00001001456. The full QTL summary statistics from this study can be accessed from http://blueprint-dev.bioinfo.cnio.es/WP10/qtls. Quantification matrices, donor metadata, Chip-seq peaks and Chip seq coverage files are available via ftp://ftp.ebi.ac.uk/pub/databases/blueprint/blueprint_Epivar/.
- DSR026HHN, DSR316KSV, DSR394HJS, DSR449MOJ, DSR853ZPR, DSR418EQU, DSR105EUT, DSR085RIY, DSR530IZI, DSR639IXJ, DSR601TID, DSR693NZP, DSR693IVW, DSR792EUZ, DSR595CTR, DSR930EID, DSR676ZHI, DSR801ZQH, DSR650UBZ, DSR804HBZ, DSR502WRJ, DSR301CXZ, DSR197ERC, DSR135HUG, DSR337BHM, DSR661WZX, DSR631VBI, DSR583OYR, DSR786EWQ, DSR840PUI