Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells.

Cell 2016 11;167(5):1398-1414.e24

Department of Human Genetics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK; Department of Haematology, University of Cambridge, Cambridge Biomedical Campus, Long Road, Cambridge CB2 0PT, UK; British Heart Foundation Centre of Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; The National Institute for Health Research Blood and Transplant Unit (NIHR BTRU) in Donor Health and Genomics at the University of Cambridge, Strangeways Research Laboratory, University of Cambridge, Wort's Causeway, Cambridge CB1 8RN, UK. Electronic address:

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.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S00928674163144
Publisher Site
http://dx.doi.org/10.1016/j.cell.2016.10.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5119954PMC
November 2016
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