Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.
Détails
ID Serval
serval:BIB_B32611E2B346
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.
Périodique
Scientific reports
Collaborateur⸱rice⸱s
EUCLIDS consortium
Contributeur⸱rice⸱s
Gormley S., Hamilton S., Herberg J., Hourmat B., Hoggart C., Kaforou M., Sancho-Shimizu V., Abdulla A., Agapow P., Bartlett M., Bellos E., Eleftherohorinou H., Galassini R., Inwald D., Mashbat M., Menikou S., Mustafa S., Nadel S., Rahman R., Thakker C., Bokhandi S., Power S., Barham H., Pathan N., Ridout J., White D., Thurston S., Faust S., Patel S., McCorkell J., Davies P., Cratev L., Navarra H., Carter S., Ramaiah R., Patel R., Tuffrey C., Gribbin A., McCready S., Peters M., Hardy K., Standing F., O'Neill L., Abelake E., Deep A., Nsirim E., Willis L., Young Z., Royad C., White S., Fortune P.M., Hudnott P., González F.Á., Barral-Arca R., Cebey-López M., Curras-Tuala M.J., García N., Vicente L.G., Gómez-Carballa A., Rial J.G., Beiroa A.G., Grande A.J., Iglesias P.L., Santos AEM, Martinón-Torres N., Sánchez JMM, Pérez B.M., Pacheco P.O., Pardo-Seco J., Pischedda S., Calle I.R., Rodríguez-Tenreiro C., Redondo-Collazo L., Fernández S.S., Silva MDSP, Vega A., Reyes S.B., León MCL, Mingorance Á.N., Barrios X.G., Vergara E.O., Torre A.C., Vivanco A., Fernández R., Sánchez F.G., Forte M.S., Rojo P., Contreras J.R., Palacios A., Navarro M., Álvarez C.Á., Lozano M.J., Carreras E., Sanagustín S.B., Neth O., Padilla MDCM, Tato LMP, Guillén S., Silveira L.F., Moreno D., van Furth AMT, van der Flier M., Boeddha N.P., Driessen GJA, Pajkrt D., Sanders EAM, van de Beek D., van der Ende A., Philipsen HLA, Adeel AOA, Breukels M.A., Brinkman DMC, de Korte CCMM, de Vries E., de Waal W.J., Dekkers R., Dings-Lammertink A., Doedens R.A., Donker A.E., Dousma M., Faber T.E., Gerrits GPJM, Gerver JAM, Heidema J., Homan-van der Veen J., Jacobs MAM, Jansen NJG, Kawczynski P., Klucovska K., Kneyber MCJ, Koopman-Keemink Y., Langenhorst V.J., Leusink J., Loza B.F., Merth I.T., Miedema C.J., Neeleman C., Noordzij J.G., Obihara C.C., van Overbeek-van Gils ALT, Poortman G.H., Potgieter S.T., Potjewijd J., Rosias PPR, Sprong T., Ten Tussher G.W., Thio B.J., Tramper-Stranders G.A., van Deuren M., van der Meer H., van Kuppevelt AJM, van Wermeskerken A.M., Verwijs W.A., Wolfs TFW, Agyeman P., Aebi C., Berger C., Giannoni E., Stocker M., Posfay-Barbe K.M., Heininger U., Bernhard-Stirnemann S., Niederer-Loher A., Kahlert C., Hasters P., Relly C., Baer W., Paulus S., Frederick H., Jennings R., Johnston J., Kenwright R., Agbeko R., Bojang K., Sarr I., Kebbeh N., Sey G., Saidykhan M., Cole F., Thomas G., Antonio M., Walcher W., Geishofer G., Klobassa D., Martin M., Pfurtscheller K., Reiter K., Rödl S., Zobel G., Zöhrer B., Töpke B., Fucik P., Gabriel M., Penzien J.M., Diab G., Miething R., Deeg K.H., Hammer J., Heininger U., Varnholt V., Schmidt A., Bindl L., Sillaber U., Huemer C., Meier P., Simic-Schleicher G., Markart M., Pfau E., Broede H., Ausserer B., Kalhoff H., Arpe V., Schweitzer-Krantz S., Kasper J.M., Loranth K., Bittrich H.J., Simma B., Klinge J., Fedlmaier M., Weigand N., Herting E., Grube R., Fusch C., Gruber A., Schimmel U., Knaufer-Schiefer S., Lässig W., Hennenberger A., von der Wense A., Tillmann R., Schwarick J., Sitzmann F.C., Streif W., Müller H., Kurnik P., Groneck P., Weiss U., Gröblacher-Roth H., Bensch J., Moser R., Schwarz R., Lenz K., Hofmann T., Göpel W., Schulz D., Berger T., Hauser E., Förster K.M., Peters J., Nicolai T.H., Kumlien B., Beckmann R., Seitz C., Hüseman D., Schürmann R., Ta V.H., Weikmann E., Evert W., Hautz J., Seidenberg J., Wocko L., Luigs P., Reiter H.L., Quietzach J., König M., Herrmann J., Mitter H., Seidler E., Maak B., Sperl W., Zwiauer K., Meissl M., Koch R., Cremer M., Breuer H.A., Görke W., Nossal R., Pernice W., Brangenberg R., Salzer H.R., Koch H., Schaller G., Paky F., Straßer F., Eitelberger F., Sontheimer D., Lischka A., Kronberger M., Dilch A., Scheibenpflug C., Bruckner R., Mahler K., Runge K., Kunze W., Schermann P.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
06/05/2019
Peer-reviewed
Oui
Volume
9
Numéro
1
Pages
6966
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Résumé
Non-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.
Mots-clé
Case-Control Studies, Cohort Studies, Genetic Association Studies, Genetic Predisposition to Disease, Genomics, High-Throughput Nucleotide Sequencing, Humans, Hypopharyngeal Neoplasms/genetics, Hypopharyngeal Neoplasms/microbiology, Hypopharyngeal Neoplasms/pathology, Meningococcal Infections/epidemiology, Meningococcal Infections/genetics, Meningococcal Infections/microbiology, Neisseria meningitidis/genetics, Neisseria meningitidis/isolation & purification, Phenotype, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid, Tumor Cells, Cultured
Pubmed
Web of science
Site de l'éditeur
Open Access
Oui
Création de la notice
01/07/2021 10:42
Dernière modification de la notice
30/10/2024 7:18
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