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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

2016; Cell Press; Volume: 167; Issue: 5 Linguagem: Inglês

10.1016/j.cell.2016.10.026

1097-4172

Lu Chen, Bing Ge, Francesco Paolo Casale, Louella Vasquez, Tony Kwan, Diego Garrido-Martín, Stephen Watt, Ying Yan, Kousik Kundu, Simone Ecker, Avik Datta, David Richardson, Frances Burden, Daniel G. Mead, Alice Mann, José M. Fernández, Sophia Rowlston, Steven P. Wilder, Samantha Farrow, Xiaojian Shao, John Lambourne, Adriana Redensek, Cornelis A. Albers, Vyacheslav Amstislavskiy, Sofie Ashford, Kim Berentsen, Lorenzo Bomba, Guillaume Bourque, David Bujold, Stephan Busche, Maxime Caron, Shu‐Huang Chen, Warren Cheung, Olivier Delaneau, Emmanouil T. Dermitzakis, Heather Elding, Irina Colgiu, Frederik Otzen Bagger, Paul Flicek, Ehsan Habibi, Valentina Iotchkova, Eva M. Janssen‐Megens, Bowon Kim, Hans Lehrach, Ernesto Lowy, Amit Mandoli, Filomena Matarese, Matthew T. Maurano, John Morris, Véra Pancaldi, Farzin Pourfarzad, Karola Rehnström, Augusto Rendon, Thomas S. Risch, Nilofar Sharifi, Marie-Michelle Simon, Marc Sultan, Alfonso Valencia, Klaudia Walter, Shuang-Yin Wang, Mattia Frontini, Stylianos E. Antonarakis, Laura Clarke, Marie‐Laure Yaspo, Stephan Beck, Roderic Guigó, Daniel Rico, Joost H.A. Martens, Willem H. Ouwehand, Taco W. Kuijpers, Dirk S. Paul, Hendrik G. Stunnenberg, Oliver Stegle, Kate Downes, Tomi Pastinen, Nicole Soranzo,

Genetic Associations and Epidemiology

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.