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International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways
International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary/genetics
2041-1723
8019
Cordell, Heather J
0c13b4c1-417f-49e5-aa74-34e1936da81a
Han, Younghun
d8e3b2b2-17a2-4017-bd45-5862cdba12cc
Mells, George F
63e52765-505a-4ae6-af08-484cf4c46059
Li, Yafang
eb6b9f4d-ab67-4732-b554-009846d8c53a
Hirschfield, Gideon M
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Greene, Casey S
88bf36c0-0c02-4d49-b133-87be571b80a6
Xie, Gang
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Juran, Brian D
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Zhu, Dakai
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Qian, David C
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Floyd, James A B
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Morley, Katherine I
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Prati, Daniele
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Lleo, Ana
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Cusi, Daniele
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Gershwin, M Eric
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Anderson, Carl A
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Lazaridis, Konstantinos N
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Invernizzi, Pietro
85aa7b41-7cbb-4be2-a51b-1f7e648b51e0
Seldin, Michael F
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Sandford, Richard N
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Amos, Christopher I
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Siminovitch, Katherine A
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Wright, Mark
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Canadian-US PBC Consortium
Cordell, Heather J
0c13b4c1-417f-49e5-aa74-34e1936da81a
Han, Younghun
d8e3b2b2-17a2-4017-bd45-5862cdba12cc
Mells, George F
63e52765-505a-4ae6-af08-484cf4c46059
Li, Yafang
eb6b9f4d-ab67-4732-b554-009846d8c53a
Hirschfield, Gideon M
bb9e925a-5674-4bad-8880-45e86f515948
Greene, Casey S
88bf36c0-0c02-4d49-b133-87be571b80a6
Xie, Gang
e0263fb8-0c53-4790-97ee-273424cfd0c0
Juran, Brian D
47f1b4e5-d5c9-4ffd-897a-0eb8a50de8e5
Zhu, Dakai
52e520c2-a583-4bd1-a1eb-56b5bea01d6d
Qian, David C
1e6e4004-e4c6-4b8d-a277-a126b237ed1f
Floyd, James A B
6ae6ddf6-c1a7-4c1c-adc0-0bedd774278b
Morley, Katherine I
30ac6bf6-07fd-4f9a-aed6-f85d286d22e8
Prati, Daniele
4139a4c7-be7a-4004-a8f7-352612df76cb
Lleo, Ana
18f78521-c492-4167-87c1-8b3ffdaa221f
Cusi, Daniele
4105812b-baf4-42a5-95c3-8a6d19810f4c
Gershwin, M Eric
670bb72b-89af-478a-857f-a110bd6bcaf4
Anderson, Carl A
68e0dafc-9613-447b-b2ab-0de4553e9289
Lazaridis, Konstantinos N
15eb810c-55f0-4f86-a48a-f6d085a0dd2a
Invernizzi, Pietro
85aa7b41-7cbb-4be2-a51b-1f7e648b51e0
Seldin, Michael F
736ac5dd-21a3-4c72-bff2-bcbd279ff2ad
Sandford, Richard N
1f9a5d2b-d14a-43b3-b326-fa9ab17b406f
Amos, Christopher I
b4e21247-1519-42f1-aa71-1adb437a2713
Siminovitch, Katherine A
8b70c32e-3c7d-41fb-9711-d5da72c42511
Wright, Mark
43325ef9-3459-4c75-b3bf-cf8d8dac2a21

Wright, Mark , Canadian-US PBC Consortium (2015) International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways. Nature Communications, 6, 8019. (doi:10.1038/ncomms9019).

Record type: Article

Abstract

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

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More information

Published date: 22 September 2015
Keywords: Genome-Wide Association Study, Humans, Liver Cirrhosis, Biliary/genetics

Identifiers

Local EPrints ID: 481103
URI: http://eprints.soton.ac.uk/id/eprint/481103
DOI: doi:10.1038/ncomms9019
ISSN: 2041-1723
PURE UUID: f8a53667-82d5-48ff-a71a-892f352054ee

Catalogue record

Date deposited: 15 Aug 2023 16:53
Last modified: 17 Mar 2024 02:13

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Contributors

Author: Heather J Cordell
Author: Younghun Han
Author: George F Mells
Author: Yafang Li
Author: Gideon M Hirschfield
Author: Casey S Greene
Author: Gang Xie
Author: Brian D Juran
Author: Dakai Zhu
Author: David C Qian
Author: James A B Floyd
Author: Katherine I Morley
Author: Daniele Prati
Author: Ana Lleo
Author: Daniele Cusi
Author: M Eric Gershwin
Author: Carl A Anderson
Author: Konstantinos N Lazaridis
Author: Pietro Invernizzi
Author: Michael F Seldin
Author: Richard N Sandford
Author: Christopher I Amos
Author: Katherine A Siminovitch
Author: Mark Wright
Corporate Author: Canadian-US PBC Consortium

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