Nick Shrine
Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
Shrine, Nick; Izquierdo, Abril G.; Chen, Jing; Packer, Richard; Hall, Robert J.; Guyatt, Anna L.; Batini, Chiara; Thompson, Rebecca J.; Pavuluri, Chandan; Malik, Vidhi; Hobbs, Brian D.; Moll, Matthew; Kim, Wonji; Tal-Singer, Ruth; Bakke, Per; Fawcett, Katherine A.; John, Catherine; Coley, Kayesha; Piga, Noemi Nicole; Pozarickij, Alfred; Lin, Kuang; Millwood, Iona Y.; Chen, Zhengming; Li, Liming; Wijnant, Sara R. A.; Lahousse, Lies; Brusselle, Guy; Uitterlinden, Andre G.; Manichaikul, Ani; Oelsner, Elizabeth C.; Rich, Stephen S.; Barr, R. Graham; Kerr, Shona M.; Vitart, Veronique; Brown, Michael R.; Wielscher, Matthias; Imboden, Medea; Jeong, Ayoung; Bartz, Traci M.; Gharib, Sina A.; Flexeder, Claudia; Karrasch, Stefan; Gieger, Christian; Peters, Annette; Stubbe, Beate; Hu, Xiaowei; Ortega, Victor E.; Meyers, Deborah A.; Bleecker, Eugene R.; Gabriel, Stacey B.; Gupta, Namrata; Smith, Albert Vernon; Luan, Jian’an; Zhao, Jing-Hua; Hansen, Ailin F.; Langhammer, Arnulf; Willer, Cristen; Bha...
Authors
Abril G. Izquierdo
Jing Chen
Richard Packer
ROBERT HALL ROBERT.HALL@NOTTINGHAM.AC.UK
Research Fellow
Anna L. Guyatt
Chiara Batini
Rebecca J. Thompson
Chandan Pavuluri
Vidhi Malik
Brian D. Hobbs
Matthew Moll
Wonji Kim
Ruth Tal-Singer
Per Bakke
Katherine A. Fawcett
Catherine John
Kayesha Coley
Noemi Nicole Piga
Alfred Pozarickij
Kuang Lin
Iona Y. Millwood
Zhengming Chen
Liming Li
Sara R. A. Wijnant
Lies Lahousse
Guy Brusselle
Andre G. Uitterlinden
Ani Manichaikul
Elizabeth C. Oelsner
Stephen S. Rich
R. Graham Barr
Shona M. Kerr
Veronique Vitart
Michael R. Brown
Matthias Wielscher
Medea Imboden
Ayoung Jeong
Traci M. Bartz
Sina A. Gharib
Claudia Flexeder
Stefan Karrasch
Christian Gieger
Annette Peters
Beate Stubbe
Xiaowei Hu
Victor E. Ortega
Deborah A. Meyers
Eugene R. Bleecker
Stacey B. Gabriel
Namrata Gupta
Albert Vernon Smith
Jian’an Luan
Jing-Hua Zhao
Ailin F. Hansen
Arnulf Langhammer
Cristen Willer
Laxmi Bhatta
David Porteous
Blair H. Smith
Archie Campbell
Tamar Sofer
Jiwon Lee
Martha L. Daviglus
Bing Yu
Elise Lim
Hanfei Xu
George T. O’Connor
Gaurav Thareja
Omar M. E. Albagha
Said I. Ismail
Wadha Al-Muftah
Radja Badji
Hamdi Mbarek
Dima Darwish
Tasnim Fadl
Heba Yasin
Maryem Ennaifar
Rania Abdellatif
Fatima Alkuwari
Muhammad Alvi
Yasser Al-Sarraj
Chadi Saad
Asmaa Althani
Eleni Fethnou
Fatima Qafoud
Eiman Alkhayat
Nahla Afifi
Sara Tomei
Wei Liu
Stephan Lorenz
Najeeb Syed
Hakeem Almabrazi
Fazulur Rehaman Vempalli
Ramzi Temanni
Tariq Abu Saqri
Mohammedhusen Khatib
Mehshad Hamza
Tariq Abu Zaid
Ahmed El Khouly
Tushar Pathare
Shafeeq Poolat
Rashid Al-Ali
Souhaila Al-Khodor
Mashael Alshafai
Ramin Badii
Lotfi Chouchane
Xavier Estivill
Khalid Fakhro
Younes Mokrab
Jithesh V. Puthen
Zohreh Tatari
Karsten Suhre
Raquel Granell
Tariq O. Faquih
Pieter S. Hiemstra
Annelies M. Slats
Benjamin H. Mullin
Jennie Hui
Alan James
John Beilby
Karina Patasova
Pirro Hysi
Jukka T. Koskela
Annah B. Wyss
Jianping Jin
Sinjini Sikdar
Mikyeong Lee
Sebastian May-Wilson
Nicola Pirastu
Katherine A. Kentistou
Peter K. Joshi
Paul R. H. J. Timmers
Alexander T. Williams
Robert C. Free
Xueyang Wang
John L. Morrison
Frank D. Gilliland
Zhanghua Chen
Carol A. Wang
Rachel E. Foong
Sarah E. Harris
Adele Taylor
Paul Redmond
James P. Cook
Anubha Mahajan
Lars Lind
Teemu Palviainen
Terho Lehtimäki
Olli T. Raitakari
Jaakko Kaprio
Taina Rantanen
Kirsi H. Pietiläinen
Simon R. Cox
Craig E. Pennell
Graham L. Hall
W. James Gauderman
Chris Brightling
James F. Wilson
Tuula Vasankari
Tarja Laitinen
Veikko Salomaa
Dennis O. Mook-Kanamori
Nicholas J. Timpson
Eleftheria Zeggini
Josée Dupuis
Caroline Hayward
Ben Brumpton
Claudia Langenberg
Stefan Weiss
Georg Homuth
Carsten Oliver Schmidt
Nicole Probst-Hensch
Marjo-Riitta Jarvelin
Alanna C. Morrison
Ozren Polasek
Igor Rudan
Joo-Hyeon Lee
Professor IAN SAYERS ian.sayers@nottingham.ac.uk
Professor of Respiratory Molecular Genetics
Emma L. Rawlins
Frank Dudbridge
Edwin K. Silverman
David P. Strachan
Robin G. Walters
Andrew P. Morris
Stephanie J. London
Michael H. Cho
Louise V. Wain
IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine
Martin D. Tobin
China Kadoorie Biobank Collaborative Group
The Qatar Genome Program Research (QGPR) Consortium
Abstract
Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
Citation
Shrine, N., Izquierdo, A. G., Chen, J., Packer, R., Hall, R. J., Guyatt, A. L., …The Qatar Genome Program Research (QGPR) Consortium. (2023). Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk. Nature Genetics, 55(3), 410-422. https://doi.org/10.1038/s41588-023-01314-0
Journal Article Type | Article |
---|---|
Acceptance Date | Jan 25, 2023 |
Online Publication Date | Mar 13, 2023 |
Publication Date | 2023-03 |
Deposit Date | Jul 31, 2023 |
Publicly Available Date | Aug 1, 2023 |
Journal | Nature Genetics |
Print ISSN | 1061-4036 |
Electronic ISSN | 1546-1718 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 55 |
Issue | 3 |
Pages | 410-422 |
DOI | https://doi.org/10.1038/s41588-023-01314-0 |
Keywords | Genetics |
Public URL | https://nottingham-repository.worktribe.com/output/18529516 |
Publisher URL | https://www.nature.com/articles/s41588-023-01314-0 |
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
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Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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