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  Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Chen, L., Ge, B., Casale, F. P., Vasquez, L., Kwan, T., Garrido-Martin, D., et al. (2016). Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells. Cell, 167(5): e24, pp. 1398-1414. doi:10.1016/j.cell.2016.10.026.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-BF2C-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-BF2D-8
Genre: Journal Article

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© 2016 The Authors

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 Creators:
Chen, L., Author
Ge, B., Author
Casale, F. P., Author
Vasquez, L., Author
Kwan, T., Author
Garrido-Martin, D., Author
Watt, S., Author
Yan, Y., Author
Kundu, K., Author
Ecker, S., Author
Datta, A., Author
Richardson, D., Author
Burden, F., Author
Mead, D., Author
Mann, A. L., Author
Fernandez, J. M., Author
Rowlston, S., Author
Wilder, S. P., Author
Farrow, S., Author
Shao, X., Author
Lambourne, J. J., AuthorRedensek, A., AuthorAlbers, C. A., AuthorAmstislavskiy, V.1, Author              Ashford, S., AuthorBerentsen, K., AuthorBomba, L., AuthorBourque, G., AuthorBujold, D., AuthorBusche, S., AuthorCaron, M., AuthorChen, S. H., AuthorCheung, W., AuthorDelaneau, O., AuthorDermitzakis, E. T., AuthorElding, H., AuthorColgiu, I., AuthorBagger, F. O., AuthorFlicek, P., AuthorHabibi, E., AuthorIotchkova, V., AuthorJanssen-Megens, E., AuthorKim, B., AuthorLehrach, H.2, Author              Lowy, E., AuthorMandoli, A., AuthorMatarese, F., AuthorMaurano, M. T., AuthorMorris, J. A., AuthorPancaldi, V., AuthorPourfarzad, F., AuthorRehnstrom, K., AuthorRendon, A., AuthorRisch, T., AuthorSharifi, N., AuthorSimon, M. M., AuthorSultan, M., AuthorValencia, A., AuthorWalter, K., AuthorWang, S. Y., AuthorFrontini, M., AuthorAntonarakis, S. E., AuthorClarke, L., AuthorYaspo, M. L.1, Author              Beck, S., AuthorGuigo, R., AuthorRico, D., AuthorMartens, J. H. A., AuthorOuwehand, W. H., AuthorKuijpers, T. W., AuthorPaul, D. S., AuthorStunnenberg, H. G., AuthorStegle, O., AuthorDownes, K., AuthorPastinen, T., AuthorSoranzo, N., Author more..
Affiliations:
1Gene Regulation and Systems Biology of Cancer (Marie-Laure Yaspo), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2117287              
2Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385697              

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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.

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Language(s): eng - English
 Dates: 2016-11-172016
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.cell.2016.10.026
ISSN: 1097-4172 (Electronic)0092-8674 (Print)
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Title: Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 167 (5) Sequence Number: e24 Start / End Page: 1398 - 1414 Identifier: ISSN: 0092-8674
CoNE: /journals/resource/954925463183