Show simple item record

dc.contributor.authorDendrou, CAen
dc.contributor.authorCortes, Aen
dc.contributor.authorShipman, Len
dc.contributor.authorEvans, HGen
dc.contributor.authorAttfield, KEen
dc.contributor.authorJostins, Len
dc.contributor.authorBarber, Ten
dc.contributor.authorKaur, Gen
dc.contributor.authorKuttikkatte, SBen
dc.contributor.authorLeach, OAen
dc.contributor.authorDesel, Cen
dc.contributor.authorFaergeman, SLen
dc.contributor.authorCheeseman, Jen
dc.contributor.authorNeville, MJen
dc.contributor.authorSawcer, Stephenen
dc.contributor.authorCompston, Alastairen
dc.contributor.authorJohnson, ARen
dc.contributor.authorEverett, Cen
dc.contributor.authorBell, JIen
dc.contributor.authorKarpe, Fen
dc.contributor.authorUltsch, Men
dc.contributor.authorEigenbrot, Cen
dc.contributor.authorMcVean, Gen
dc.contributor.authorFugger, Len
dc.date.accessioned2017-02-23T09:39:11Z
dc.date.available2017-02-23T09:39:11Z
dc.date.issued2016-11-02en
dc.identifier.issn1946-6234
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/262725
dc.description.abstractThousands of genetic variants have been identified, which contribute to the development of complex diseases, but determining how to elucidate their biological consequences for translation into clinical benefit is challenging. Conflicting evidence regarding the functional impact of genetic variants in the tyrosine kinase 2 ($\textit{TYK2}$) gene, which is differentially associated with common autoimmune diseases, currently obscures the potential of TYK2 as a therapeutic target. We aimed to resolve this conflict by performing genetic meta-analysis across disorders; subsequent molecular, cellular, in vivo, and structural functional follow-up; and epidemiological studies. Our data revealed a protective homozygous effect that defined a signaling optimum between autoimmunity and immunodeficiency and identified TYK2 as a potential drug target for certain common autoimmune disorders.
dc.description.sponsorshipWork in the authors’ laboratories is supported by the U.K. and Danish MRCs, the Alan and Babette Sainsbury Charitable Fund, the Naomi Bramson Trust, the Clinical Neuroimmunology Fund, the Oxford BRC, the Oak Foundation (L.F.), the Rosetrees Trust (L.F. and C.A.D.), and the Wellcome Trust (100308/Z/12/Z and 106130/Z/14/Z to L.F. and 100956/Z/13/Z to G.M.). L.S. was supported by a Christopher Welch Scholarship.
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Association for the Advancement of Science
dc.titleResolving $\textit{TYK2}$ locus genotype-to-phenotype differences in autoimmunityen
dc.typeArticle
prism.issueIdentifier363en
prism.number363ra149en
prism.publicationDate2016en
prism.publicationNameScience Translational Medicineen
prism.volume8en
dc.identifier.doi10.17863/CAM.8015
dcterms.dateAccepted2016-10-14en
rioxxterms.versionofrecord10.1126/scitranslmed.aag1974en
rioxxterms.versionAMen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2016-11-02en
dc.contributor.orcidSawcer, Stephen [0000-0001-7685-0974]
dc.identifier.eissn1946-6242
rioxxterms.typeJournal Article/Reviewen
rioxxterms.freetoread.startdate2017-05-02


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record