Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.

TitleWhole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.
Publication TypeJournal Article
Year of Publication2020
AuthorsZhao, X, Qiao, D, Yang, C, Kasela, S, Kim, W, Ma, Y, Shrine, N, Batini, C, Sofer, T, Taliun, SAGagliano, Sakornsakolpat, P, Balte, PP, Prokopenko, D, Yu, B, Lange, LA, Dupuis, J, Cade, BE, Lee, J, Gharib, SA, Daya, M, Laurie, CA, Ruczinski, I, L Cupples, A, Loehr, LR, Bartz, TM, Morrison, AC, Psaty, BM, Vasan, RS, Wilson, JG, Taylor, KD, Durda, P, W Johnson, C, Cornell, E, Guo, X, Liu, Y, Tracy, RP, Ardlie, KG, Aguet, F, VanDenBerg, DJ, Papanicolaou, GJ, Rotter, JI, Barnes, KC, Jain, D, Nickerson, DA, Muzny, DM, Metcalf, GA, Doddapaneni, H, Dugan-Perez, S, Gupta, N, Gabriel, S, Rich, SS, O'Connor, GT, Redline, S, Reed, RM, Laurie, CC, Daviglus, ML, Preudhomme, LK, Burkart, KM, Kaplan, RC, Wain, LV, Tobin, MD, London, SJ, Lappalainen, T, Oelsner, EC, Abecasis, GR, Silverman, EK, R Barr, G, Cho, MH, Manichaikul, A
Corporate AuthorsNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Lung Working Group
JournalNat Commun
Volume11
Issue1
Pagination5182
Date Published2020 10 14
ISSN2041-1723
KeywordsAdult, African Americans, Aged, Aged, 80 and over, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Calcium-Binding Proteins, Feasibility Studies, Female, Follow-Up Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Lung, Male, Middle Aged, Polymorphism, Single Nucleotide, Protein Inhibitors of Activated STAT, Pulmonary Disease, Chronic Obstructive, Respiratory Physiological Phenomena, Small Ubiquitin-Related Modifier Proteins, Whole Genome Sequencing
Abstract

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.

DOI10.1038/s41467-020-18334-7
Alternate JournalNat Commun
PubMed ID33057025
PubMed Central IDPMC7598941
Grant ListHHSN268201100037C / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
R01 HL077612 / HL / NHLBI NIH HHS / United States
HHSN268201800001C / HL / NHLBI NIH HHS / United States
R21 HL129924 / HL / NHLBI NIH HHS / United States
R01 HL137927 / HL / NHLBI NIH HHS / United States
U01 HL117626 / HL / NHLBI NIH HHS / United States
R01 HL131565 / HL / NHLBI NIH HHS / United States
R01 HL147148 / HL / NHLBI NIH HHS / United States
R01 HL089856 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
R01 HL135142 / HL / NHLBI NIH HHS / United States
R21 HL121457 / HL / NHLBI NIH HHS / United States
R35 HL135818 / HL / NHLBI NIH HHS / United States
R01 HL098433 / HL / NHLBI NIH HHS / United States
HHSN268201500015C / HL / NHLBI NIH HHS / United States
R01 HL142028 / HL / NHLBI NIH HHS / United States
HHSN268201500014C / HL / NHLBI NIH HHS / United States
K01 HL129039 / HL / NHLBI NIH HHS / United States
R01 HL117626 / HL / NHLBI NIH HHS / United States
K23 HL130627 / HL / NHLBI NIH HHS / United States