Publication

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

EUCLIDS Consortium, Borghini, L., Png, E., Binder, A., Wright, V. J., Pinnock, E., de Groot, R., Hazelzet, J., Emonts, M., Van der Flier, M., Schlapbach, L. J., Anderson, S., Secka, F., Salas, A., Fink, C., Carrol, E. D., Pollard, A. J., Coin, L. J., Kuijpers, T. W., Martinon-Torres, F., Zenz, W., Levin, M., Hibberd, M. L. & Davila, S., 6-May-2019, In : Scientific Reports. 9, 15 p., 6966.

Research output: Contribution to journalArticleAcademicpeer-review

APA

EUCLIDS Consortium, Borghini, L., Png, E., Binder, A., Wright, V. J., Pinnock, E., de Groot, R., Hazelzet, J., Emonts, M., Van der Flier, M., Schlapbach, L. J., Anderson, S., Secka, F., Salas, A., Fink, C., Carrol, E. D., Pollard, A. J., Coin, L. J., Kuijpers, T. W., ... Davila, S. (2019). Identification of regulatory variants associated with genetic susceptibility to meningococcal disease. Scientific Reports, 9, [6966]. https://doi.org/10.1038/s41598-019-43292-6

Author

EUCLIDS Consortium ; Borghini, Lisa ; Png, Eileen ; Binder, Alexander ; Wright, Victoria J. ; Pinnock, Ellie ; de Groot, Ronald ; Hazelzet, Jan ; Emonts, Marieke ; Van der Flier, Michiel ; Schlapbach, Luregn J. ; Anderson, Suzanne ; Secka, Fatou ; Salas, Antonio ; Fink, Colin ; Carrol, Enitan D. ; Pollard, Andrew J. ; Coin, Lachlan J. ; Kuijpers, Taco W. ; Martinon-Torres, Federico ; Zenz, Werner ; Levin, Michael ; Hibberd, Martin L. ; Davila, Sonia. / Identification of regulatory variants associated with genetic susceptibility to meningococcal disease. In: Scientific Reports. 2019 ; Vol. 9.

Harvard

EUCLIDS Consortium, Borghini, L, Png, E, Binder, A, Wright, VJ, Pinnock, E, de Groot, R, Hazelzet, J, Emonts, M, Van der Flier, M, Schlapbach, LJ, Anderson, S, Secka, F, Salas, A, Fink, C, Carrol, ED, Pollard, AJ, Coin, LJ, Kuijpers, TW, Martinon-Torres, F, Zenz, W, Levin, M, Hibberd, ML & Davila, S 2019, 'Identification of regulatory variants associated with genetic susceptibility to meningococcal disease', Scientific Reports, vol. 9, 6966. https://doi.org/10.1038/s41598-019-43292-6

Standard

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease. / EUCLIDS Consortium; Borghini, Lisa; Png, Eileen; Binder, Alexander; Wright, Victoria J.; Pinnock, Ellie; de Groot, Ronald; Hazelzet, Jan; Emonts, Marieke; Van der Flier, Michiel; Schlapbach, Luregn J.; Anderson, Suzanne; Secka, Fatou; Salas, Antonio; Fink, Colin; Carrol, Enitan D.; Pollard, Andrew J.; Coin, Lachlan J.; Kuijpers, Taco W.; Martinon-Torres, Federico; Zenz, Werner; Levin, Michael; Hibberd, Martin L.; Davila, Sonia.

In: Scientific Reports, Vol. 9, 6966, 06.05.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

EUCLIDS Consortium, Borghini L, Png E, Binder A, Wright VJ, Pinnock E et al. Identification of regulatory variants associated with genetic susceptibility to meningococcal disease. Scientific Reports. 2019 May 6;9. 6966. https://doi.org/10.1038/s41598-019-43292-6


BibTeX

@article{f9e4c4bc55424ce5abf3d7251d0794eb,
title = "Identification of regulatory variants associated with genetic susceptibility to meningococcal disease",
abstract = "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 nasopharyngea I 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.",
keywords = "SEQUENCE VARIATION, KAPPA-B, GENOME, BINDING",
author = "{EUCLIDS Consortium} and Lisa Borghini and Eileen Png and Alexander Binder and Wright, {Victoria J.} and Ellie Pinnock and {de Groot}, Ronald and Jan Hazelzet and Marieke Emonts and {Van der Flier}, Michiel and Schlapbach, {Luregn J.} and Suzanne Anderson and Fatou Secka and Antonio Salas and Colin Fink and Carrol, {Enitan D.} and Pollard, {Andrew J.} and Coin, {Lachlan J.} and Kuijpers, {Taco W.} and Federico Martinon-Torres and Werner Zenz and Michael Levin and Hibberd, {Martin L.} and Sonia Davila and Stuart Gormley and Shea Hamilton and Jethro Herberg and Bernardo Hourmat and Clive Hoggart and Myrsini Kaforou and Vanessa Sancho-Shimizu and Amina Abdulla and Paul Agapow and Maeve Bartlett and Evangelos Bellos and Hariklia Eleftherohorinou and {van der Flier}, M. and Brinkman, {D. M. C.} and {de Vries}, E. and Doedens, {R. A.} and Donker, {A. E.} and Faber, {T. E.} and Gerrits, {G. P. J. M.} and Jacobs, {M. A. M.} and Kneyber, {M. C. J.} and Jansen, {N. J. G.} and {van Overbeek-van Gils}, {A. L. T.} and Poortman, {G. H.} and {van der Meer}, H. and Andreas Schmidt and Johannes-Martin Kasper",
year = "2019",
month = may,
day = "6",
doi = "10.1038/s41598-019-43292-6",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

AU - EUCLIDS Consortium

AU - Borghini, Lisa

AU - Png, Eileen

AU - Binder, Alexander

AU - Wright, Victoria J.

AU - Pinnock, Ellie

AU - de Groot, Ronald

AU - Hazelzet, Jan

AU - Emonts, Marieke

AU - Van der Flier, Michiel

AU - Schlapbach, Luregn J.

AU - Anderson, Suzanne

AU - Secka, Fatou

AU - Salas, Antonio

AU - Fink, Colin

AU - Carrol, Enitan D.

AU - Pollard, Andrew J.

AU - Coin, Lachlan J.

AU - Kuijpers, Taco W.

AU - Martinon-Torres, Federico

AU - Zenz, Werner

AU - Levin, Michael

AU - Hibberd, Martin L.

AU - Davila, Sonia

AU - Gormley, Stuart

AU - Hamilton, Shea

AU - Herberg, Jethro

AU - Hourmat, Bernardo

AU - Hoggart, Clive

AU - Kaforou, Myrsini

AU - Sancho-Shimizu, Vanessa

AU - Abdulla, Amina

AU - Agapow, Paul

AU - Bartlett, Maeve

AU - Bellos, Evangelos

AU - Eleftherohorinou, Hariklia

AU - van der Flier, M.

AU - Brinkman, D. M. C.

AU - de Vries, E.

AU - Doedens, R. A.

AU - Donker, A. E.

AU - Faber, T. E.

AU - Gerrits, G. P. J. M.

AU - Jacobs, M. A. M.

AU - Kneyber, M. C. J.

AU - Jansen, N. J. G.

AU - van Overbeek-van Gils, A. L. T.

AU - Poortman, G. H.

AU - van der Meer, H.

AU - Schmidt, Andreas

AU - Kasper, Johannes-Martin

PY - 2019/5/6

Y1 - 2019/5/6

N2 - 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 nasopharyngea I 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.

AB - 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 nasopharyngea I 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.

KW - SEQUENCE VARIATION

KW - KAPPA-B

KW - GENOME

KW - BINDING

U2 - 10.1038/s41598-019-43292-6

DO - 10.1038/s41598-019-43292-6

M3 - Article

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 6966

ER -

ID: 84290205