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dc.contributor.authorBorghini, L.
dc.contributor.authorPng, E.
dc.contributor.authorBinder, A.
dc.contributor.authorWright, V. J.
dc.contributor.authorPinnock, E.
dc.contributor.authorde Groot, R.
dc.contributor.authorHazelzet, J.
dc.contributor.authorEmonts, M.
dc.contributor.authorVan der Flier, M.
dc.contributor.authorSchlapbach, L. J.
dc.contributor.authorAnderson, S.
dc.contributor.authorSecka, F.
dc.contributor.authorSalas, A.
dc.contributor.authorFink, C.
dc.contributor.authorCarrol, E. D.
dc.contributor.authorPollard, A. J.
dc.contributor.authorCoin, L. J.
dc.contributor.authorKuijpers, T. W.
dc.contributor.authorMartinón Torres, Federico 
dc.contributor.authorZenz, W.
dc.contributor.authorLevin, M.
dc.contributor.authorHibberd, M. L.
dc.contributor.authorDavila, S.
dc.date.accessioned2021-09-29T12:43:23Z
dc.date.available2021-09-29T12:43:23Z
dc.date.issued2019
dc.identifier.issn2045-2322
dc.identifier.otherhttps://www.ncbi.nlm.nih.gov/pubmed/31061469es
dc.identifier.urihttp://hdl.handle.net/20.500.11940/15380
dc.description.abstractNon-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes.en
dc.language.isoeng
dc.rightsAtribución 4.0 Internacional
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.meshHumans*
dc.subject.meshGenetic Association Studies*
dc.subject.meshMeningococcal Infections*
dc.subject.meshPhenotype*
dc.subject.meshHigh-Throughput Nucleotide Sequencing*
dc.subject.meshHypopharyngeal Neoplasms*
dc.subject.meshCase-Control Studies*
dc.subject.meshGenomics*
dc.subject.meshGenetic Predisposition to Disease*
dc.subject.meshNeisseria meningitidis*
dc.subject.meshCohort Studies*
dc.titleIdentification of regulatory variants associated with genetic susceptibility to meningococcal diseasees
dc.typeArtigoes
dc.contributor.authorcorpEUCLIDS Consortium
dc.authorsophosBorghini, L.
dc.authorsophosPng, E.
dc.authorsophosBinder, A.
dc.authorsophosWright, V. J.
dc.authorsophosPinnock, E.
dc.authorsophosde Groot, R.
dc.authorsophosHazelzet, J.
dc.authorsophosEmonts, M.
dc.authorsophosVan der Flier, M.
dc.authorsophosSchlapbach, L. J.
dc.authorsophosAnderson, S.
dc.authorsophosSecka, F.
dc.authorsophosSalas, A.
dc.authorsophosFink, C.
dc.authorsophosCarrol, E. D.
dc.authorsophosPollard, A. J.
dc.authorsophosCoin, L. J.
dc.authorsophosKuijpers, T. W.
dc.authorsophosMartinon-Torres, F.
dc.authorsophosZenz, W.
dc.authorsophosLevin, M.
dc.authorsophosHibberd, M. L.
dc.authorsophosDavila, S.
dc.authorsophosconsortium, EUCLIDS
dc.identifier.doi10.1038/s41598-019-43292-6
dc.identifier.pmid31061469
dc.identifier.sophos30598
dc.issue.number1es
dc.journal.titleScientific Reportses
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago de Compostela - Hospital da Barbanza::Pediatría
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS)
dc.page.initial6966es
dc.relation.publisherversionhttps://spiral.imperial.ac.uk:8443/bitstream/10044/1/70371/5/s41598-019-43292-6.pdf
dc.rights.accessRightsopenAccess
dc.subject.decsfenotipo*
dc.subject.decsinfecciones meningocócicas*
dc.subject.decsestudios de asociación genética*
dc.subject.decsestudios de casos y controles*
dc.subject.decsneoplasias hipofaríngeas*
dc.subject.decsgenómica*
dc.subject.decssecuenciación de nucleótidos de alto rendimiento*
dc.subject.decsNeisseria meningitidis*
dc.subject.decshumanos*
dc.subject.decsestudios de cohortes*
dc.subject.decspredisposición genética a la enfermedad*
dc.subject.keywordCHUS
dc.subject.keywordIDIS
dc.typefidesArtículo Científico (incluye Original, Original breve, Revisión Sistemática y Meta-análisis)
dc.typesophosArtículo Original
dc.volume.number9es


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Atribución 4.0 Internacional
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