TY - JOUR
T1 - Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants
AU - NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
AU - TOPMed Lung Working Group
AU - Zhao, Xutong
AU - Qiao, Dandi
AU - Yang, Chaojie
AU - Kasela, Silva
AU - Kim, Wonji
AU - Ma, Yanlin
AU - Shrine, Nick
AU - Batini, Chiara
AU - Sofer, Tamar
AU - Taliun, Sarah A.Gagliano
AU - Sakornsakolpat, Phuwanat
AU - Balte, Pallavi P.
AU - Prokopenko, Dmitry
AU - Yu, Bing
AU - Lange, Leslie A.
AU - Dupuis, Josée
AU - Cade, Brian E.
AU - Lee, Jiwon
AU - Gharib, Sina A.
AU - Daya, Michelle
AU - Laurie, Cecelia A.
AU - Ruczinski, Ingo
AU - Cupples, L. Adrienne
AU - Loehr, Laura R.
AU - Bartz, Traci M.
AU - Morrison, Alanna C.
AU - Psaty, Bruce M.
AU - Vasan, Ramachandran S.
AU - Wilson, James G.
AU - Taylor, Kent D.
AU - Durda, Peter
AU - Johnson, W. Craig
AU - Cornell, Elaine
AU - Guo, Xiuqing
AU - Liu, Yongmei
AU - Tracy, Russell P.
AU - Ardlie, Kristin G.
AU - Aguet, François
AU - VanDenBerg, David J.
AU - Papanicolaou, George J.
AU - Rotter, Jerome I.
AU - Barnes, Kathleen C.
AU - Jain, Deepti
AU - Nickerson, Deborah A.
AU - Muzny, Donna M.
AU - Metcalf, Ginger A.
AU - Doddapaneni, Harshavardhan
AU - Dugan-Perez, Shannon
AU - Gupta, Namrata
AU - Kaplan, Robert C.
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Chronic 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.
AB - Chronic 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.
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U2 - 10.1038/s41467-020-18334-7
DO - 10.1038/s41467-020-18334-7
M3 - Article
C2 - 33057025
AN - SCOPUS:85093476366
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5182
ER -