Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants
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Published:2020-10-14
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zhao XutongORCID, Qiao Dandi, Yang Chaojie, Kasela SilvaORCID, Kim Wonji, Ma Yanlin, Shrine NickORCID, Batini Chiara, Sofer TamarORCID, Taliun Sarah A. GaglianoORCID, Sakornsakolpat PhuwanatORCID, Balte Pallavi P., Prokopenko Dmitry, Yu Bing, Lange Leslie A., Dupuis JoséeORCID, Cade Brian E.ORCID, Lee JiwonORCID, Gharib Sina A., Daya MichelleORCID, Laurie Cecelia A.ORCID, Ruczinski Ingo, Cupples L. AdrienneORCID, Loehr Laura R., Bartz Traci M., Morrison Alanna C., Psaty Bruce M., Vasan Ramachandran S.ORCID, Wilson James G., Taylor Kent D.ORCID, Durda Peter, Johnson W. Craig, Cornell Elaine, Guo Xiuqing, Liu Yongmei, Tracy Russell P.ORCID, Ardlie Kristin G., Aguet FrançoisORCID, VanDenBerg David J.ORCID, Papanicolaou George J., Rotter Jerome I.ORCID, Barnes Kathleen C.ORCID, Jain Deepti, Nickerson Deborah A., Muzny Donna M., Metcalf Ginger A., Doddapaneni HarshavardhanORCID, Dugan-Perez Shannon, Gupta Namrata, Gabriel Stacey, Rich Stephen S.ORCID, O’Connor George T., Redline Susan, Reed Robert M., Laurie Cathy C., Daviglus Martha L., Preudhomme Liana K., Burkart Kristin M., Kaplan Robert C., Wain Louise V.ORCID, Tobin Martin D., London Stephanie J.ORCID, Lappalainen TuuliORCID, Oelsner Elizabeth C., Abecasis Goncalo R.ORCID, Silverman Edwin K., Barr R. Graham, Cho Michael H.ORCID, Manichaikul AniORCID, ,
Abstract
AbstractChronic obstructive pulmonary disease (COPD), diagnosed by reduced lung function, is a leading cause of morbidity and mortality. We performed whole genome sequence (WGS) analysis of lung function and COPD in a multi-ethnic sample of 11,497 participants from population- and family-based studies, and 8499 individuals from COPD-enriched studies in the NHLBI Trans-Omics for Precision Medicine (TOPMed) Program. We identify at genome-wide significance 10 known GWAS loci and 22 distinct, previously unreported loci, including two common variant signals from stratified analysis of African Americans. Four novel common variants within the regions of PIAS1, RGN (two variants) and FTO show evidence of replication in the UK Biobank (European ancestry n ~ 320,000), while colocalization analyses leveraging multi-omic data from GTEx and TOPMed identify potential molecular mechanisms underlying four of the 22 novel loci. Our study demonstrates the value of performing WGS analyses and multi-omic follow-up in cohorts of diverse ancestry.
Funder
U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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