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dc.contributor.authorLee, M. N.
dc.contributor.authorYe, C.
dc.contributor.authorVillani, A.-C.
dc.contributor.authorRaj, T.
dc.contributor.authorLi, W.
dc.contributor.authorEisenhaure, Thomas
dc.contributor.authorImboywa, S. H.
dc.contributor.authorChipendo, P. I.
dc.contributor.authorSlowikowski, K.
dc.contributor.authorRaddassi, K.
dc.contributor.authorMcCabe, C.
dc.contributor.authorLee, M. H.
dc.contributor.authorFrohlich, I. Y.
dc.contributor.authorRaychaudhuri, S.
dc.contributor.authorStranger, B. E.
dc.contributor.authorBenoist, Christophe
dc.contributor.authorDe Jager, Philip L.
dc.contributor.authorHacohen, Nir
dc.contributor.authorRan, F. Ann
dc.contributor.authorZhang, Feng
dc.contributor.authorRegev, Aviv
dc.contributor.authorHafler, David A.
dc.contributor.authorWard, Lucas D.
dc.contributor.authorKellis, Manolis
dc.date.accessioned2015-04-22T15:43:50Z
dc.date.available2015-04-22T15:43:50Z
dc.date.issued2014-03
dc.date.submitted2013-10
dc.identifier.issn0036-8075
dc.identifier.issn1095-9203
dc.identifier.urihttp://hdl.handle.net/1721.1/96695
dc.description.abstractLittle is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.en_US
dc.description.sponsorshipNational Human Genome Research Institute (U.S.) (Grant P50 HG006193)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.). Pioneer Award (DP1 CA174427)en_US
dc.description.sponsorshipHoward Hughes Medical Instituteen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Grant HG004037)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.). Pioneer Award (DP1 MH100706)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Transformative R01 Grant R01 DK097768)en_US
dc.description.sponsorshipW. M. Keck Foundationen_US
dc.description.sponsorshipMcKnight Foundationen_US
dc.description.sponsorshipMerkin, Richard N.en_US
dc.description.sponsorshipDamon Runyon Cancer Research Foundationen_US
dc.description.sponsorshipSearle Scholars Programen_US
dc.description.sponsorshipSimons Foundationen_US
dc.language.isoen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofhttp://dx.doi.org/10.1126/science.1246980en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleCommon Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cellsen_US
dc.typeArticleen_US
dc.identifier.citationLee, M. N., C. Ye, A.-C. Villani, T. Raj, W. Li, T. M. Eisenhaure, S. H. Imboywa, et al. “Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells.” Science 343, no. 6175 (March 6, 2014): 1246980–1246980.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratoryen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciencesen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Electrical Engineering and Computer Scienceen_US
dc.contributor.departmentMcGovern Institute for Brain Research at MITen_US
dc.contributor.mitauthorZhang, Fengen_US
dc.contributor.mitauthorRan, F. Annen_US
dc.contributor.mitauthorRegev, Aviven_US
dc.contributor.mitauthorHafler, David A.en_US
dc.contributor.mitauthorWard, Lucas D.en_US
dc.contributor.mitauthorKellis, Manolisen_US
dc.relation.journalScienceen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsLee, M. N.; Ye, C.; Villani, A.-C.; Raj, T.; Li, W.; Eisenhaure, T. M.; Imboywa, S. H.; Chipendo, P. I.; Ran, F. A.; Slowikowski, K.; Ward, L. D.; Raddassi, K.; McCabe, C.; Lee, M. H.; Frohlich, I. Y.; Hafler, D. A.; Kellis, M.; Raychaudhuri, S.; Zhang, F.; Stranger, B. E.; Benoist, C. O.; De Jager, P. L.; Regev, A.; Hacohen, N.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2782-2509
dc.identifier.orcidhttps://orcid.org/0000-0001-8567-2049
dc.identifier.orcidhttps://orcid.org/0000-0002-8017-809X
mit.licenseOPEN_ACCESS_POLICYen_US
mit.metadata.statusComplete


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