Imperial College London
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ProfessorSimonTaylor-Robinson

Faculty of Engineering, Department of Electrical and Electronic Engineering

Visiting Professor
 
 
 
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s.taylor-robinson

 
 
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Electrical EngineeringSouth Kensington Campus

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Publications

Citation

BibTex format

@article{Cordell:2021:10.1016/j.jhep.2021.04.055,
author = {Cordell, HJ and Fryett, JJ and Ueno, K and Darlay, R and Aiba, Y and Hitomi, Y and Kawashima, M and Nishida, N and Khor, S-S and Gervais, O and Kawai, Y and Nagasaki, M and Tokunaga, K and Tang, R and Shi, Y and Li, Z and Juran, BD and Atkinson, EJ and Gerussi, A and Carbone, M and Asselta, R and Cheung, A and de, Andrade M and Baras, A and Horowitz, J and Ferreira, MAR and Sun, D and Jones, DE and Flack, S and Spicer, A and Mulcahy, VL and Byan, J and Han, Y and Sandford, RN and Lazaridis, KN and Amos, C and Hirschfield, GM and Seldin, MF and Invernizzi, P and Siminovitch, KA and Ma, X and Nakamura, M and Mells, GF},
doi = {10.1016/j.jhep.2021.04.055},
journal = {Journal of Hepatology},
pages = {572--581},
title = {An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugs},
url = {http://dx.doi.org/10.1016/j.jhep.2021.04.055},
volume = {75},
year = {2021}
}
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TY  - JOUR
AB  - Backgrounds & AimsPrimary biliary cholangitis (PBC) is a chronic liver disease in which autoimmune destruction of the small intrahepatic bile ducts eventually leads to cirrhosis. Many patients have inadequate response to licensed medications, motivating the search for novel therapies. Previous genome-wide association studies (GWAS) and meta-analyses (GWMA) of PBC have identified numerous risk loci for this condition, providing insight into its aetiology. We undertook the largest GWMA of PBC to date, aiming to identify additional risk loci and prioritise candidate genes for in silico drug efficacy screening.MethodsWe combined new and existing genotype data for 10,516 cases and 20,772 controls from 5 European and 2 East Asian cohorts.ResultsWe identified 56 genome-wide significant loci (20 novel) including 46 in European, 13 in Asian, and 41 in combined cohorts; and a 57th genome-wide significant locus (also novel) in conditional analysis of the European cohorts. Candidate genes at newly identified loci include FCRL3, INAVA, PRDM1, IRF7, CCR6, CD226, and IL12RB1, which each play key roles in immunity. Pathway analysis reiterated the likely importance of pattern recognition receptor and TNF signalling, JAK-STAT signalling, and differentiation of T helper (TH)1 and TH17 cells in the pathogenesis of this disease. Drug efficacy screening identified several medications predicted to be therapeutic in PBC, some of which are well-established in the treatment of other autoimmune disorders.ConclusionsThis study has identified additional risk loci for PBC, provided a hierarchy of agents that could be trialled in this condition, and emphasised the value of genetic and genomic approaches to drug discovery in complex disorders.Lay summaryPrimary biliary cholangitis (PBC) is a chronic liver disease that eventually leads to cirrhosis. In this study, we analysed genetic information from 10,516 people with PBC and 20,772 healthy individuals recruited in Canada, China, Italy, Japan
AU  - Cordell,HJ
AU  - Fryett,JJ
AU  - Ueno,K
AU  - Darlay,R
AU  - Aiba,Y
AU  - Hitomi,Y
AU  - Kawashima,M
AU  - Nishida,N
AU  - Khor,S-S
AU  - Gervais,O
AU  - Kawai,Y
AU  - Nagasaki,M
AU  - Tokunaga,K
AU  - Tang,R
AU  - Shi,Y
AU  - Li,Z
AU  - Juran,BD
AU  - Atkinson,EJ
AU  - Gerussi,A
AU  - Carbone,M
AU  - Asselta,R
AU  - Cheung,A
AU  - de,Andrade M
AU  - Baras,A
AU  - Horowitz,J
AU  - Ferreira,MAR
AU  - Sun,D
AU  - Jones,DE
AU  - Flack,S
AU  - Spicer,A
AU  - Mulcahy,VL
AU  - Byan,J
AU  - Han,Y
AU  - Sandford,RN
AU  - Lazaridis,KN
AU  - Amos,C
AU  - Hirschfield,GM
AU  - Seldin,MF
AU  - Invernizzi,P
AU  - Siminovitch,KA
AU  - Ma,X
AU  - Nakamura,M
AU  - Mells,GF
DO  - 10.1016/j.jhep.2021.04.055
EP  - 581
PY  - 2021///
SN  - 0168-8278
SP  - 572
TI  - An international genome-wide meta-analysis of primary biliary cholangitis: novel risk loci and candidate drugs
T2  - Journal of Hepatology
UR  - http://dx.doi.org/10.1016/j.jhep.2021.04.055
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000686978100008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.journal-of-hepatology.eu/article/S0168-8278(21)00334-2/fulltext
UR  - http://hdl.handle.net/10044/1/94943
VL  - 75
ER  -
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