GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 08 2022
17 08 2022
Historique:
received:
25
11
2020
accepted:
08
04
2022
entrez:
17
8
2022
pubmed:
18
8
2022
medline:
20
8
2022
Statut:
epublish
Résumé
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
Identifiants
pubmed: 35977952
doi: 10.1038/s41467-022-29931-z
pii: 10.1038/s41467-022-29931-z
pmc: PMC9385867
doi:
Substances chimiques
Bile Acids and Salts
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
4840Subventions
Organisme : British Heart Foundation
ID : FS/18/53/33863
Pays : United Kingdom
Organisme : Medical Research Council
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Investigateurs
Julian Adlard
(J)
Munaza Ahmed
(M)
Tim Aitman
(T)
Hana Alachkar
(H)
David Allsup
(D)
Jeff Almeida-King
(J)
Philip Ancliff
(P)
Richard Antrobus
(R)
Ruth Armstrong
(R)
Gavin Arno
(G)
Sofie Ashford
(S)
William Astle
(W)
Anthony Attwood
(A)
Chris Babbs
(C)
Tamam Bakchoul
(T)
Tadbir Bariana
(T)
Julian Barwell
(J)
David Bennett
(D)
David Bentley
(D)
Agnieszka Bierzynska
(A)
Tina Biss
(T)
Marta Bleda
(M)
Harm Bogaard
(H)
Christian Bourne
(C)
Sara Boyce
(S)
John Bradley
(J)
Gerome Breen
(G)
Paul Brennan
(P)
Carole Brewer
(C)
Matthew Brown
(M)
Michael Browning
(M)
Rachel Buchan
(R)
Matthew Buckland
(M)
Teofila Bueser
(T)
Siobhan Burns
(S)
Oliver Burren
(O)
Paul Calleja
(P)
Gerald Carr-White
(G)
Keren Carss
(K)
Ruth Casey
(R)
Mark Caulfield
(M)
John Chambers
(J)
Jennifer Chambers
(J)
Floria Cheng
(F)
Patrick F Chinnery
(PF)
Martin Christian
(M)
Colin Church
(C)
Naomi Clements Brod
(NC)
Gerry Coghlan
(G)
Elizabeth Colby
(E)
Trevor Cole
(T)
Janine Collins
(J)
Peter Collins
(P)
Camilla Colombo
(C)
Robin Condliffe
(R)
Stuart Cook
(S)
Terry Cook
(T)
Nichola Cooper
(N)
Paul Corris
(P)
Abigail Crisp-Hihn
(A)
Nicola Curry
(N)
Cesare Danesino
(C)
Matthew Daniels
(M)
Louise Daugherty
(L)
John Davis
(J)
Sri V V Deevi
(SVV)
Timothy Dent
(T)
Eleanor Dewhurst
(E)
Peter Dixon
(P)
Kate Downes
(K)
Anna Drazyk
(A)
Elizabeth Drewe
(E)
Tina Dutt
(T)
David Edgar
(D)
Karen Edwards
(K)
William Egner
(W)
Wendy Erber
(W)
Marie Erwood
(M)
Maria C Estiu
(MC)
Gillian Evans
(G)
Dafydd Gareth Evans
(DG)
Tamara Everington
(T)
Mélanie Eyries
(M)
Remi Favier
(R)
Debra Fletcher
(D)
James Fox
(J)
Amy Frary
(A)
Courtney French
(C)
Kathleen Freson
(K)
Mattia Frontini
(M)
Daniel Gale
(D)
Henning Gall
(H)
Claire Geoghegan
(C)
Terry Gerighty
(T)
Stefano Ghio
(S)
Hossein-Ardeschir Ghofrani
(HA)
Simon Gibbs
(S)
Kimberley Gilmour
(K)
Barbara Girerd
(B)
Sarah Goddard
(S)
Keith Gomez
(K)
Pavels Gordins
(P)
David Gosal
(D)
Stefan Gräf
(S)
Luigi Grassi
(L)
Daniel Greene
(D)
Lynn Greenhalgh
(L)
Andreas Greinacher
(A)
Paolo Gresele
(P)
Philip Griffiths
(P)
Sofia Grigoriadou
(S)
Russell Grocock
(R)
Detelina Grozeva
(D)
Scott Hackett
(S)
Charaka Hadinnapola
(C)
William Hague
(W)
Matthias Haimel
(M)
Matthew Hall
(M)
Helen Hanson
(H)
Kirsty Harkness
(K)
Andrew Harper
(A)
Claire Harris
(C)
Daniel Hart
(D)
Ahamad Hassan
(A)
Grant Hayman
(G)
Alex Henderson
(A)
Jonathan Hoffmann
(J)
Rita Horvath
(R)
Arjan Houweling
(A)
Luke Howard
(L)
Fengyuan Hu
(F)
Gavin Hudson
(G)
Joseph Hughes
(J)
Aarnoud Huissoon
(A)
Marc Humbert
(M)
Sean Humphray
(S)
Sarah Hunter
(S)
Matthew Hurles
(M)
Louise Izatt
(L)
Roger James
(R)
Sally Johnson
(S)
Stephen Jolles
(S)
Jennifer Jolley
(J)
Neringa Jurkute
(N)
Mary Kasanicki
(M)
Hanadi Kazkaz
(H)
Rashid Kazmi
(R)
Peter Kelleher
(P)
David Kiely
(D)
Nathalie Kingston
(N)
Robert Klima
(R)
Myrto Kostadima
(M)
Gabor Kovacs
(G)
Ania Koziell
(A)
Roman Kreuzhuber
(R)
Taco Kuijpers
(T)
Ajith Kumar
(A)
Dinakantha Kumararatne
(D)
Manju Kuria
(M)
Michael Laffa
(M)
Fiona Lalloo
(F)
Michele Lamber
(M)
Hana Lango Alle
(HL)
Allan Lawrie
(A)
Mark Layton
(M)
Claire Lentaigne
(C)
Adam Levine
(A)
Rachel Linger
(R)
Hilary Longhurst
(H)
Eleni Louka
(E)
Robert MacKenzie Ross
(RM)
Bella Madan
(B)
Eamonn Maher
(E)
Jesmeen Maimaris
(J)
Sarah Mangles
(S)
Rutendo Mapeta
(R)
Kevin Marchbank
(K)
Stephen Marks
(S)
Hugh S Markus
(HS)
Andrew Marshall
(A)
Jennifer Martin
(J)
Mary Mathias
(M)
Emma Matthews
(E)
Heather Maxwell
(H)
Paul McAlinden
(P)
Mark McCarthy
(M)
Stuart Meacham
(S)
Adam Mead
(A)
Karyn Megy
(K)
Sarju Mehta
(S)
Michel Michaelides
(M)
Carolyn Millar
(C)
Shahin Moledina
(S)
David Montani
(D)
Tony Moor
(T)
Nicholas Morrell
(N)
Keith Muir
(K)
Andrew Mumford
(A)
Michael Newnham
(M)
Jennifer O'Sullivan
(J)
Samya Obaji
(S)
Steven Okoli
(S)
Andrea Olschewski
(A)
Horst Olschewski
(H)
Kai Ren Ong
(KR)
Elizabeth Ormondroy
(E)
Willem Ouwehan
(W)
Sofia Papadi
(S)
Soo-Mi Park
(SM)
David Parry
(D)
Joan Paterson
(J)
Andrew Peacock
(A)
John Peden
(J)
Kathelijne Peerlinck
(K)
Christopher Penkett
(C)
Joanna Pepke-Zaba
(J)
Romina Petersen
(R)
Angela Pyle
(A)
Stuart Rankin
(S)
Anupama Rao
(A)
F Lucy Raymond
(FL)
Paula Rayner-Matthew
(P)
Christine Rees
(C)
Augusto Rendon
(A)
Tara Renton
(T)
Andrew Rice
(A)
Sylvia Richardson
(S)
Alex Richter
(A)
Irene Roberts
(I)
Catherine Roughley
(C)
Noemi Roy
(N)
Omid Sadeghi-Alavijeh
(O)
Moin Saleem
(M)
Nilesh Samani
(N)
Alba Sanchis-Juan
(A)
Ravishankar Sargur
(R)
Simon Satchell
(S)
Sinisa Savic
(S)
Laura Scelsi
(L)
Sol Schulman
(S)
Marie Scully
(M)
Claire Searle
(C)
Werner Seeger
(W)
Carrock Sewell
(C)
Denis Seyres
(D)
Susie Shapiro
(S)
Olga Sharmardina
(O)
Rakefet Shtoyerman
(R)
Keith Sibson
(K)
Lucy Side
(L)
Ilenia Simeoni
(I)
Michael Simpson
(M)
Suthesh Sivapalaratnam
(S)
Anne-Bine Skytte
(AB)
Katherine Smith
(K)
Kenneth G C Smith
(KGC)
Katie Snape
(K)
Florent Soubrier
(F)
Simon Staines
(S)
Emily Staples
(E)
Hannah Stark
(H)
Jonathan Stephens
(J)
Kathleen Stirrups
(K)
Sophie Stock
(S)
Jay Suntharalingam
(J)
Emilia Swietlik
(E)
R Campbell Tait
(RC)
Kate Talks
(K)
Rhea Tan
(R)
James Thaventhiran
(J)
Andreas Themistocleous
(A)
Moira Thomas
(M)
Kate Thomson
(K)
Adrian Thrasher
(A)
Chantal Thys
(C)
Marc Tischkowitz
(M)
Catherine Titterton
(C)
Cheng-Hock Toh
(CH)
Mark Toshner
(M)
Matthew Traylor
(M)
Carmen Treacy
(C)
Richard Trembath
(R)
Salih Tuna
(S)
Wojciech Turek
(W)
Ernest Turro
(E)
Tom Vale
(T)
Chris Van Geet
(C)
Natalie Van Zuydam
(N)
Marta Vazquez-Lopez
(M)
Julie von Ziegenweidt
(J)
Anton Vonk Noordegraaf
(A)
Quintin Waisfisz
(Q)
Suellen Walker
(S)
James Ware
(J)
Hugh Watkins
(H)
Christopher Watt
(C)
Andrew Webster
(A)
Wei Wei
(W)
Steven Welch
(S)
Julie Wessels
(J)
Sarah Westbury
(S)
John-Paul Westwood
(JP)
John Wharton
(J)
Deborah Whitehorn
(D)
James Whitworth
(J)
Martin R Wilkins
(MR)
Edwin Wong
(E)
Nicholas Wood
(N)
Yvette Wood
(Y)
Geoff Woods
(G)
Emma Woodward
(E)
Stephen Wort
(S)
Austen Worth
(A)
Katherine Yates
(K)
Patrick Yong
(P)
Tim Young
(T)
Ping Yu
(P)
Patrick Yu-Wai-Man
(P)
J C Ambrose
(JC)
P Arumugam
(P)
R Bevers
(R)
M Bleda
(M)
F Boardman-Pretty
(F)
C R Boustred
(CR)
H Brittain
(H)
M A Brown
(MA)
M J Caulfield
(MJ)
G C Chan
(GC)
T Fowler
(T)
A Giess
(A)
A Hamblin
(A)
S Henderson
(S)
T J P Hubbard
(TJP)
R Jackson
(R)
L J Jones
(LJ)
D Kasperaviciute
(D)
M Kayikci
(M)
A Kousathanas
(A)
L Lahnstein
(L)
S E A Leigh
(SEA)
I U S Leong
(IUS)
F J Lopez
(FJ)
F Maleady-Crowe
(F)
M McEntagart
(M)
F Minneci
(F)
L Moutsianas
(L)
M Mueller
(M)
N Murugaesu
(N)
A C Need
(AC)
P O'Donovan
(P)
C A Odhams
(CA)
C Patch
(C)
D Perez-Gil
(D)
M B Pereira
(MB)
J Pullinger
(J)
T Rahim
(T)
A Rendon
(A)
T Rogers
(T)
K Savage
(K)
K Sawant
(K)
R H Scott
(RH)
A Siddiq
(A)
A Sieghart
(A)
S C Smith
(SC)
A Sosinsky
(A)
A Stuckey
(A)
M Tanguy
(M)
A L Taylor Tavares
(AL)
E R A Thomas
(ERA)
S R Thompson
(SR)
A Tucci
(A)
M J Welland
(MJ)
E Williams
(E)
K Witkowska
(K)
S M Wood
(SM)
Informations de copyright
© 2022. The Author(s).
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