Imperial College London
Dr Victoria Wright

DrVictoriaWright

Faculty of Medicine, Department of Infectious Disease

Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 3577v.wright

 
 
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Location

 

PaediatricsMedical SchoolSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Borghini:2019:10.1038/s41598-019-43292-6,
author = {Borghini, L and Png, E and Binder, A and Wright, VJ and Pinnock, E and de, Groot R and Hazelzet, J and Emonts, M and Van, der Flier M and Schlapbach, LJ and Anderson, S and Secka, F and Salas, A and Fink, C and Carrol, ED and Pollard, AJ and Coin, LJ and Kuijpers, TW and Martinon-Torres, F and Zenz, W and Levin, M and Hibberd, ML and Davila, S and Gormley, S and Hamilton, S and Herberg, J and Hourmat, B and Hoggart, C and Kaforou, M and Sancho-Shimizu, V and Abdulla, A and Agapow, P and Bartlett, M and Bellos, E and Eleftherohorinou, H and Galassini, R and Inwald, D and Mashbat, M and Menikou, S and Mustafa, S and Nadel, S and Rahman, R and Thakker, C and Bokhandi, S and Power, S and Barham, H and Pathan, N and Ridout, J and White, D and Thurston, S and Faust, S and Patel, S and McCorkell, J and Davies, P and Cratev, L and Navarra, H and Carter, S and Ramaiah, R and Patel, R and Tuffrey, C and Gribbin, A and McCready, S and Peters, M and Hardy, K and Standing, F and O'Neill, L and Abel},
doi = {10.1038/s41598-019-43292-6},
journal = {Scientific Reports},
title = {Identification of regulatory variants associated with genetic susceptibility to meningococcal disease},
url = {http://dx.doi.org/10.1038/s41598-019-43292-6},
volume = {9},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
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 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.
AU  - Borghini,L
AU  - Png,E
AU  - Binder,A
AU  - Wright,VJ
AU  - Pinnock,E
AU  - de,Groot R
AU  - Hazelzet,J
AU  - Emonts,M
AU  - Van,der Flier M
AU  - Schlapbach,LJ
AU  - Anderson,S
AU  - Secka,F
AU  - Salas,A
AU  - Fink,C
AU  - Carrol,ED
AU  - Pollard,AJ
AU  - Coin,LJ
AU  - Kuijpers,TW
AU  - Martinon-Torres,F
AU  - Zenz,W
AU  - Levin,M
AU  - Hibberd,ML
AU  - Davila,S
AU  - Gormley,S
AU  - Hamilton,S
AU  - Herberg,J
AU  - Hourmat,B
AU  - Hoggart,C
AU  - Kaforou,M
AU  - Sancho-Shimizu,V
AU  - Abdulla,A
AU  - Agapow,P
AU  - Bartlett,M
AU  - Bellos,E
AU  - Eleftherohorinou,H
AU  - Galassini,R
AU  - Inwald,D
AU  - Mashbat,M
AU  - Menikou,S
AU  - Mustafa,S
AU  - Nadel,S
AU  - Rahman,R
AU  - Thakker,C
AU  - Bokhandi,S
AU  - Power,S
AU  - Barham,H
AU  - Pathan,N
AU  - Ridout,J
AU  - White,D
AU  - Thurston,S
AU  - Faust,S
AU  - Patel,S
AU  - McCorkell,J
AU  - Davies,P
AU  - Cratev,L
AU  - Navarra,H
AU  - Carter,S
AU  - Ramaiah,R
AU  - Patel,R
AU  - Tuffrey,C
AU  - Gribbin,A
AU  - McCready,S
AU  - Peters,M
AU  - Hardy,K
AU  - Standing,F
AU  - O'Neill,L
AU  - Abelake,E
AU  - Deep,A
AU  - Nsirim,E
AU  - Willis,L
AU  - Young,Z
AU  - Royad,C
AU  - White,S
AU  - Fortune,PM
AU  - Hudnott,P
AU  - Alvez,Gonzalez F
AU  - Barral-Arca,R
AU  - Cebey-Lopez,M
AU  - Jose,Curras-Tuala M
AU  - Garcia,N
AU  - Garcia,Vicente L
AU  - Gomez-Carballa,A
AU  - Gomez,Rial J
AU  - Grela,Beiroa A
AU  - Justicia,Grande A
AU  - Leborans,Iglesias P
AU  - Martinez,Santos AE
AU  - Martinon-Torres,N
AU  - Martinon,Sanchez JM
AU  - Mosquera,Perez B
AU  - Obando,Pacheco P
AU  - Pardo-Seco,J
AU  - Pischedda,S
AU  - Rivero,Calle I
AU  - Rodriguez-Tenreiro,C
AU  - Redondo-Collazo,L
AU  - Seren,Fernandez S
AU  - Porto,Silva MDS
AU  - Vega,A
AU  - Beatriz,Reyes S
AU  - Leon,Leon MC
AU  - Navarro,Mingorance A
AU  - Gabaldo,Barrios X
AU  - Onate,Vergara E
AU  - Concha,Torre A
AU  - Vivanco,A
AU  - Fernandez,R
AU  - Gimenez,Sanchez F
AU  - Sanchez,Forte M
AU  - Rojo,P
AU  - Ruiz,Contreras J
AU  - Palacios,A
AU  - Navarro,M
AU  - Alvarez,Alvarez C
AU  - Jose,Lozano M
AU  - Carreras,E
AU  - Brio,Sanagustin S
AU  - Neth,O
AU  - Martinez,Padilla MDC
AU  - Prieto,Tato LM
AU  - Guillen,S
AU  - Fernandez,Silveira L
AU  - Moreno,D
AU  - van,Furth AMT
AU  - van,der Flier M
AU  - Boeddha,NP
AU  - Driessen,GJA
AU  - Pajkrt,D
AU  - Sanders,EAM
AU  - van,de Beek D
AU  - van,der Ende A
AU  - Philipsen,HLA
AU  - Adeel,AOA
AU  - Breukels,MA
AU  - Brinkman,DMC
AU  - de,Korte CCMM
AU  - de,Vries E
AU  - de,Waal WJ
AU  - Dekkers,R
AU  - Dings-Lammertink,A
AU  - Doedens,RA
AU  - Donker,AE
AU  - Dousma,M
AU  - Faber,TE
AU  - Gerrits,GPJM
AU  - Gerver,JAM
AU  - Heidema,J
AU  - Homan-van,der Veen J
AU  - Jacobs,MAM
AU  - Jansen,NJG
AU  - Kawczynski,P
AU  - Klucovska,K
AU  - Kneyber,MCJ K
DO  - 10.1038/s41598-019-43292-6
PY  - 2019///
SN  - 2045-2322
TI  - Identification of regulatory variants associated with genetic susceptibility to meningococcal disease
T2  - Scientific Reports
UR  - http://dx.doi.org/10.1038/s41598-019-43292-6
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000466878900066&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/70371
VL  - 9
ER  -
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