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A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis

dc.creatorMadireddy L., Patsopoulos N.A., Cotsapas C., Bos S.D., Beecham A., McCauley J., Kim K., Jia X., Santaniello A., Caillier S.J., Andlauer T.F.M., Barcellos L.F., Berge T., Bernardinelli L., Martinelli-Boneschi F., Booth D.R., Briggs F., Celius E.G., Comabella M., Comi G., Cree B.A.C., D’Alfonso S., Dedham K., Duquette P., Efthimios D., Esposito F., Fontaine B., Gasperi C., Goris A., Dubois B., Gourraud P.-A., Hadjigeorgiou G., Haines J., Hawkins C., Hemmer B., Hintzen R., Horakova D., Isobe N., Kalra S., Kira J.-I., Khalil M., Kockum I., Lill C.M., Lincoln M.R., Luessi F., Martin R., Oturai A., Palotie A., Pericak-Vance M.A., Henry R., Saarela J., Ivinson A., Olsson T., Taylor B.V., Stewart G.J., Harbo H.F., Compston A., Hauser S.L., Hafler D.A., Zipp F., De Jager P., Sawcer S., Oksenberg J.R., Baranzini S.E., International Multiple Sclerosis Genetics Consortiumen
dc.date.accessioned2023-01-31T08:55:38Z
dc.date.available2023-01-31T08:55:38Z
dc.date.issued2019
dc.identifier10.1038/s41467-019-09773-y
dc.identifier.issn20411723
dc.identifier.urihttp://hdl.handle.net/11615/76058
dc.description.abstractGenome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available. © 2019, The Author(s).en
dc.language.isoenen
dc.sourceNature Communicationsen
dc.source.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85066046672&doi=10.1038%2fs41467-019-09773-y&partnerID=40&md5=bf802fb6b93f5e1f404c4c9fa060db3a
dc.subjectCD14 antigenen
dc.subjectCD19 antigenen
dc.subjectCD3 antigenen
dc.subjectCD4 antigenen
dc.subjectCD8 antigenen
dc.subjecttranscription factor FOXP3en
dc.subjecttranscriptomeen
dc.subjectArticleen
dc.subjectB lymphocyteen
dc.subjectbinding siteen
dc.subjectcase control studyen
dc.subjectCD4+ T lymphocyteen
dc.subjectCD8+ T lymphocyteen
dc.subjectcontrolled studyen
dc.subjectfluorescence activated cell sortingen
dc.subjectgene expressionen
dc.subjectgene regulatory networken
dc.subjectgenetic associationen
dc.subjectgenetic regulationen
dc.subjectgenetic risken
dc.subjectgenetic susceptibilityen
dc.subjectgenome-wide association studyen
dc.subjecthumanen
dc.subjectimmune responseen
dc.subjectmajor clinical studyen
dc.subjectmultiple sclerosisen
dc.subjectprotein interactionen
dc.subjectprotein phosphorylationen
dc.subjectregulatory T lymphocyteen
dc.subjectRNA sequenceen
dc.subjectsignal transductionen
dc.subjectsingle nucleotide polymorphismen
dc.subjectTh1 cellen
dc.subjectTh17 cellen
dc.subjectTh2 cellen
dc.subjecttranscriptomicsen
dc.subjectNature Publishing Groupen
dc.titleA systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosisen
dc.typejournalArticleen


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