@article{9d3b1dd68dfa402099db78d904d43607,
title = "Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk",
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.",
author = "{China Kadoorie Biobank Collaborative Group} and Nick Shrine and Izquierdo, {Abril G} and Jing Chen and Richard Packer and Hall, {Robert J} and Guyatt, {Anna L} and Chiara Batini and Thompson, {Rebecca J} and Chandan Pavuluri and Vidhi Malik and Hobbs, {Brian D} and Matthew Moll and Wonji Kim and Ruth Tal-Singer and Per Bakke and Fawcett, {Katherine A} and Catherine John and Kayesha Coley and Piga, {Noemi Nicole} and Alfred Pozarickij and Kuang Lin and Millwood, {Iona Y} and Zhengming Chen and Liming Li and Wijnant, {Sara R A} and Lies Lahousse and Guy Brusselle and Uitterlinden, {Andre G} and Ani Manichaikul and Oelsner, {Elizabeth C} and Rich, {Stephen S} and Barr, {R Graham} and Kerr, {Shona M} and Veronique Vitart and Brown, {Michael R} and Matthias Wielscher and Medea Imboden and Ayoung Jeong and Bartz, {Traci M} and Gharib, {Sina A} and Claudia Flexeder and Stefan Karrasch and Christian Gieger and Annette Peters and Beate Stubbe and Xiaowei Hu and Ortega, {Victor E} and Meyers, {Deborah A} and Bleecker, {Eugene R} and Gabriel, {Stacey B} and Namrata Gupta and Smith, {Albert Vernon} and Jian'an Luan and Jing-Hua Zhao and Hansen, {Ailin F} and Arnulf Langhammer and Cristen Willer and Laxmi Bhatta and David Porteous and Smith, {Blair H} and Archie Campbell and Tamar Sofer and Jiwon Lee and Daviglus, {Martha L} and Bing Yu and Elise Lim and Hanfei Xu and O'Connor, {George T} and Gaurav Thareja and Albagha, {Omar M E} and Karsten Suhre and Raquel Granell and Faquih, {Tariq O} and Hiemstra, {Pieter S} and Slats, {Annelies M} and Mullin, {Benjamin H} and Jennie Hui and Alan James and John Beilby and Karina Patasova and Pirro Hysi and Koskela, {Jukka T} and Wyss, {Annah B} and Jianping Jin and Sinjini Sikdar and Mikyeong Lee and Sebastian May-Wilson and Nicola Pirastu and Kentistou, {Katherine A} and Joshi, {Peter K} and Timmers, {Paul R H J} and Williams, {Alexander T} and Free, {Robert C} and Xueyang Wang and Morrison, {John L} and Gilliland, {Frank D} and Zhanghua Chen and Wang, {Carol A} and Foong, {Rachel E} and Harris, {Sarah E} and Adele Taylor and Paul Redmond and Cook, {James P} and Anubha Mahajan and Lars Lind and Teemu Palviainen and Terho Lehtim{\"a}ki and Raitakari, {Olli T} and Jaakko Kaprio and Taina Rantanen and Pietil{\"a}inen, {Kirsi H} and Cox, {Simon R.} and Pennell, {Craig E} and Hall, {Graham L} and Gauderman, {W James} and Chris Brightling and Wilson, {James F} and Tuula Vasankari and Tarja Laitinen and Veikko Salomaa and Mook-Kanamori, {Dennis O} and Timpson, {Nicholas J} and Eleftheria Zeggini and Jos{\'e}e Dupuis and Caroline Hayward and Ben Brumpton and Claudia Langenberg and Stefan Weiss and Georg Homuth and Schmidt, {Carsten Oliver} and Nicole Probst-Hensch and Marjo-Riitta Jarvelin and Morrison, {Alanna C} and Ozren Polasek and Igor Rudan and Joo-Hyeon Lee and Ian Sayers and Rawlins, {Emma L} and Frank Dudbridge and Silverman, {Edwin K} and Strachan, {David P} and Walters, {Robin G} and Morris, {Andrew P} and London, {Stephanie J} and Cho, {Michael H} and Wain, {Louise V} and Hall, {Ian P} and Tobin, {Martin D}",
note = "Publisher Copyright: {\textcopyright} 2023. The Author(s).",
year = "2023",
month = mar,
day = "13",
doi = "10.1038/s41588-023-01314-0",
language = "English",
volume = "55",
pages = "410--422",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}