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

نویسندگان

  • Heather J. Cordell
  • Younghun Han
  • George F. Mells
  • Yafang Li
  • Gideon M. Hirschfield
  • Casey S. Greene
  • Gang Xie
  • Brian D. Juran
  • Dakai Zhu
  • David C. Qian
  • James A. B. Floyd
  • Katherine I. Morley
  • Daniele Prati
  • Ana Lleo
  • Daniele Cusi
  • Erik M Schlicht
  • Craig Lammert
  • Elizabeth J Atkinson
  • Landon L Chan
  • Mariza de Andrade
  • Tobias Balschun
  • Andrew L Mason
  • Robert P Myers
  • Jinyi Zhang
  • Piotr Milkiewicz
  • Jia Qu
  • Joseph A Odin
  • Velimir A Luketic
  • Bruce R Bacon
  • Henry C Bodenheimer Jr
  • Valentina Liakina
  • Catherine Vincent
  • Cynthia Levy
  • Peter K Gregersen
  • Piero L Almasio
  • Domenico Alvaro
  • Pietro Andreone
  • Angelo Andriulli
  • Cristina Barlassina
  • Pier Maria Battezzati
  • Antonio Benedetti
  • Francesca Bernuzzi
  • Ilaria Bianchi
  • Maria Consiglia Bragazzi
  • Maurizia Brunetto
  • Savino Bruno
  • Giovanni Casella
  • Barbara Coco
  • Agostino Colli
  • Massimo Colombo
  • Silvia Colombo
  • Carmela Cursaro
  • Lory Saveria Crocè
  • Andrea Crosignani
  • Maria Francesca Donato
  • Gianfranco Elia
  • Luca Fabris
  • Carlo Ferrari
  • Annarosa Floreani
  • Barbara Foglieni
  • Rosanna Fontana
  • Andrea Galli
  • Roberta Lazzari
  • Fabio Macaluso
  • Federica Malinverno
  • Fabio Marra
  • Marco Marzioni
  • Alberto Mattalia
  • Renzo Montanari
  • Lorenzo Morini
  • Filomena Morisco
  • Mousa Hani S
  • Luigi Muratori
  • Paolo Muratori
  • Grazia A Niro
  • Vincenzo O Palmieri
  • Antonio Picciotto
  • Mauro Podda
  • Piero Portincasa
  • Vincenzo Ronca
  • Floriano Rosina
  • Sonia Rossi
  • Ilaria Sogno
  • Giancarlo Spinzi
  • Marta Spreafico
  • Mario Strazzabosco
  • Sonia Tarallo
  • Mirko Tarocchi
  • Claudio Tiribelli
  • Pierluigi Toniutto
  • Maria Vinci
  • Massimo Zuin
  • Chin Lye Ch'ng
  • Mesbah Rahman
  • Tom Yapp
  • Richard Sturgess
  • Christopher Healey
  • Marek Czajkowski
  • Anton Gunasekera
  • Pranab Gyawali
  • Purushothaman Premchand
  • Kapil Kapur
  • Richard Marley
  • Graham Foster
  • Alan Watson
  • Aruna Dias
  • Javaid Subhani
  • Rory Harvey
  • Roger McCorry
  • David Ramanaden
  • Jaber Gasem
  • Richard Evans
  • Thiriloganathan Mathialahan
  • Christopher Shorrock
  • George Lipscomb
  • Paul Southern
  • Jeremy Tibble
  • David Gorard
  • Altaf Palegwala
  • Susan Jones
  • Marco Carbone
  • Mohamed Dawwas
  • Graeme Alexander
  • Sunil Dolwani
  • Martin Prince
  • Matthew Foxton
  • David Elphick
  • Harriet Mitchison
  • Ian Gooding
  • Mazn Karmo
  • Sushma Saksena
  • Mike Mendall
  • Minesh Patel
  • Roland Ede
  • Andrew Austin
  • Joanna Sayer
  • Lorraine Hankey
  • Christopher Hovell
  • Neil Fisher
  • Martyn Carter
  • Konrad Koss
  • Andrzej Piotrowicz
  • Charles Grimley
  • David Neal
  • Guan Lim
  • Sass Levi
  • Aftab Ala
  • Andrea Broad
  • Athar Saeed
  • Gordon Wood
  • Jonathan Brown
  • Mark Wilkinson
  • Harriet Gordon
  • John Ramage
  • Jo Ridpath
  • Theodore Ngatchu
  • Bob Grover
  • Syed Shaukat
  • Ray Shidrawi
  • George Abouda
  • Faiz Ali
  • Ian Rees
  • Imroz Salam
  • Mark Narain
  • Ashley Brown
  • Simon Taylor-Robinson
  • Simon Williams
  • Leonie Grellier
  • Paul Banim
  • Debashis Das
  • Andrew Chilton
  • Michael Heneghan
  • Howard Curtis
  • Markus Gess
  • Ian Drake
  • Mark Aldersley
  • Mervyn Davies
  • Rebecca Jones
  • Alastair McNair
  • Raj Srirajaskanthan
  • Maxton Pitcher
  • Sambit Sen
  • George Bird
  • Adrian Barnardo
  • Paul Kitchen
  • Kevin Yoong
  • Oza Chirag
  • Nurani Sivaramakrishnan
  • George MacFaul
  • David Jones
  • Amir Shah
  • Chris Evans
  • Subrata Saha
  • Katharine Pollock
  • Peter Bramley
  • Ashis Mukhopadhya
  • Andrew Fraser
  • Peter Mills
  • Christopher Shallcross
  • Stewart Campbell
  • Andrew Bathgate
  • Alan Shepherd
  • John Dillon
  • Simon Rushbrook
  • Robert Przemioslo
  • Christopher Macdonald
  • Jane Metcalf
  • Udi Shmueli
  • Andrew Davis
  • Asifabbas Naqvi
  • Tom Lee
  • Stephen D Ryder
  • Jane Collier
  • Howard Klass
  • Mary Ninkovic
  • Matthew Cramp
  • Nicholas Sharer
  • Richard Aspinall
  • Patrick Goggin
  • Deb Ghosh
  • Andrew Douds
  • Barbara Hoeroldt
  • Jonathan Booth
  • Earl Williams
  • Hyder Hussaini
  • William Stableforth
  • Reuben Ayres
  • Douglas Thorburn
  • Eileen Marshall
  • Andrew Burroughs
  • Steven Mann
  • Martin Lombard
  • Paul Richardson
  • Imran Patanwala
  • Julia Maltby
  • Matthew Brookes
  • Ray Mathew
  • Samir Vyas
  • Saket Singhal
  • Dermot Gleeson
  • Sharat Misra
  • Jeff Butterworth
  • Keith George
  • Tim Harding
  • Andrew Douglass
  • Simon Panter
  • Jeremy Shearman
  • Gary Bray
  • Graham Butcher
  • Daniel Forton
  • John Mclindon
  • Matthew Cowan
  • Gregory Whatley
  • Aditya Mandal
  • Hemant Gupta
  • Pradeep Sanghi
  • Sanjiv Jain
  • Steve Pereira
  • Geeta Prasad
  • Gill Watts
  • Mark Wright
  • James Neuberger
  • Fiona Gordon
  • Esther Unitt
  • Allister Grant
  • Toby Delahooke
  • Andrew Higham
  • Alison Brind
  • Mark Cox
  • Subramaniam Ramakrishnan
  • Alistair King
  • Carole Collins
  • Simon Whalley
  • Andy Li
  • Jocelyn Fraser
  • Andrew Bell
  • Voi Shim Wong
  • Amit Singhal
  • Ian Gee
  • Yeng Ang
  • Rupert Ransford
  • James Gotto
  • Charles Millson
  • Jane Bowles
  • Caradog Thomas
  • Melanie Harrison
  • Roman Galaska
  • Jennie Kendall
  • Jessica Whiteman
  • Caroline Lawlor
  • Catherine Gray
  • Keith Elliott
  • Caroline Mulvaney-Jones
  • Lucie Hobson
  • Greta Van Duyvenvoorde
  • Alison Loftus
  • Katie Seward
  • Ruth Penn
  • Jane Maiden
  • Rose Damant
  • Janeane Hails
  • Rebecca Cloudsdale
  • Valeria Silvestre
  • Sue Glenn
  • Eleanor Dungca
  • Natalie Wheatley
  • Helen Doyle
  • Melanie Kent
  • Caroline Hamilton
  • Delyth Braim
  • Helen Wooldridge
  • Rachel Abrahams
  • Alison Paton
  • Nicola Lancaster
  • Andrew Gibbins
  • Karen Hogben
  • Phillipa Desousa
  • Florin Muscariu
  • Janine Musselwhite
  • Alexandra McKay
  • LaiTing Tan
  • Carole Foale
  • Jacqueline Brighton
  • Kerry Flahive
  • Estelle Nambela
  • Paula Townshend
  • Chris Ford
  • Sophie Holder
  • Caroline Palmer
  • James Featherstone
  • Mariam Nasseri
  • Joy Sadeghian
  • Bronwen Williams
  • Carol Thomas
  • Sally-Ann Rolls
  • Abigail Hynes
  • Claire Duggan
  • Sarah Jones
  • Mary Crossey
  • Glynis Stansfield
  • Carolyn MacNicol
  • Joy Wilkins
  • Elva Wilhelmsen
  • Parizade Raymode
  • Hye-Jeong Lee
  • Emma Durant
  • Rebecca Bishop
  • Noma Ncube
  • Sherill Tripoli
  • Rebecca Casey
  • Caroline Cowley
  • Richard Miller
  • Kathryn Houghton
  • Samantha Ducker
  • Fiona Wright
  • Bridget Bird
  • Gwen Baxter
  • Janie Keggans
  • Maggie Hughes
  • Emma Grieve
  • Karin Young
  • D Williams
  • Kate Ocker
  • Frances Hines
  • Kirsty Martin
  • Caron Innes
  • Talal Valliani
  • Helen Fairlamb
  • Sarah Thornthwaite
  • Anne Eastick
  • Elizabeth Tanqueray
  • Jennifer Morrison
  • Becky Holbrook
  • Julie Browning
  • Kirsten Walker
  • Susan Congreave
  • Juliette Verheyden
  • Susan Slininger
  • Lizzie Stafford
  • Denise O'Donnell
  • Mark Ainsworth
  • Susan Lord
  • Linda Kent
  • Linda March
  • Christine Dickson
  • Diane Simpson
  • Beverley Longhurst
  • Maria Hayes
  • Ervin Shpuza
  • Nikki White
  • Sarah Besley
  • Sallyanne Pearson
  • Alice Wright
  • Linda Jones
  • Emma Gunter
  • Hannah Dewhurst
  • Anna Fouracres
  • Liz Farrington
  • Lyn Graves
  • Suzie Marriott
  • Marina Leoni
  • David Tyrer
  • Kate Martin
  • Lola Dali-kemmery
  • Victoria Lambourne
  • Marie Green
  • Dawn Sirdefield
  • Kelly Amor
  • Julie Colley
  • Bal Shinder
  • Jayne Jones
  • Marisa Mills
  • Mandy Carnahan
  • Natalie Taylor
  • Kerenza Boulton
  • Julie Tregonning
  • Carly Brown
  • Gayle Clifford
  • Emily Archer
  • Maria Hamilton
  • Janette Curtis
  • Tracey Shewan
  • Sue Walsh
  • Karen Warner
  • Kimberley Netherton
  • Mcdonald Mupudzi
  • Bridget Gunson
  • Jane Gitahi
  • Denise Gocher
  • Sally Batham
  • Hilary Pateman
  • Senayon Desmennu
  • Jill Conder
  • Darren Clement
  • Susan Gallagher
  • Jacky Orpe
  • PuiChing Chan
  • Lynn Currie
  • Lynn O'Donohoe
  • Metod Oblak
  • Lisa Morgan
  • Marie Quinn
  • Isobel Amey
  • Yolanda Baird
  • Donna Cotterill
  • Lourdes Cumlat
  • Louise Winter
  • Sandra Greer
  • Katie Spurdle
  • Joanna Allison
  • Simon Dyer
  • Helen Sweeting
  • Jean Kordula
  • M. Eric Gershwin
  • Carl A. Anderson
  • Konstantinos N. Lazaridis
  • Pietro Invernizzi
  • Michael F. Seldin
  • Richard N. Sandford
  • Christopher I. Amos
  • Katherine A. Siminovitch
چکیده

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.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density

Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide signif...

متن کامل

A genome-wide association study identifies six novel risk loci for primary biliary cholangitis

Primary biliary cholangitis (PBC) is an autoimmune liver disease with a strong hereditary component. Here, we report a genome-wide association study that included 1,122 PBC cases and 4,036 controls of Han Chinese descent, with subsequent replication in a separate cohort of 907 PBC cases and 2,127 controls. Our results show genome-wide association of 14 PBC risk loci including previously identif...

متن کامل

A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set of loci that passed genome-wide significance in the first stage GWA scan. However, the second stag...

متن کامل

Genome-wide Association Study to Identify Genes and Biological Pathways Associated with Type Traits in Cattle using Pathway Analysis

Extended Abstract Introduction and Objective: Type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlate with other economically important traits in cattle including fertility, longevity and carcass traits. The present study aimed to conduct a genome wide association studies (GWAS) based on gene-set enrichment analysis for identifying the ...

متن کامل

Immunochip analyses identify a novel risk locus for primary biliary cirrhosis at 13q14, multiple independent associations at four established risk loci and epistasis between 1p31 and 7q32 risk variants.

To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provi...

متن کامل

Hearing function and thresholds: a genome-wide association study in European isolated populations identifies new loci and pathways.

BACKGROUND Hearing is a complex trait, but until now only a few genes are known to contribute to variability of this process. In order to discover genes and pathways that underlie auditory function, a genome-wide association study was carried out within the International Consortium G-EAR. METHODS Meta-analysis of genome-wide association study's data from six isolated populations of European a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2015