Lin Chen
Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function
Chen, Lin; Tang, Wenbo; Kowgier, Matthew; Loth, Daan W.; Soler Artigas, Mar?a; Joubert, Bonnie R.; Hodge, Emily; Gharib, Sina A.; Smith, Albert V.; Ruczinski, Ingo; Gudnason, Vilmundur; Mathias, Rasika A.; Harris, Tamara B.; Hansel, Nadia N.; Launer, Lenore J.; Barnes, Kathleen C.; Hansen, Joyanna G.; Albrecht, Eva; Aldrich, Melinda C.; Allerhand, Michael; Barr, R. Graham; Brusselle, Guy G.; Couper, David J.; Curjuric, Ivan; Davies, Gail; Deary, Ian J.; Dupuis, Jos?e; Fall, Tove; Foy, Millennia; Franceschini, Nora; Gao, Wei; Gl?ser, Sven; Gu, Xiangjun; Hancock, Dana B.; Heinrich, Joachim; Hofman, Albert; Imboden, Medea; Ingelsson, Erik; James, Alan; Karrasch, Stefan; Koch, Beate; Kritchevsky, Stephen B.; Kumar, Ashish; Lahousse, Lies; Li, Guo; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Lohman, Kurt; Lumley, Thomas; McArdle, Wendy L.; Meibohm, Bernd; Morris, Andrew P.; Morrison, Alanna C.; Musk, Bill; North, Kari E.; Palmer, Lyle J.; Probst-Hensch, Nicole M.; Psaty, Bruce M.; Rivadene...
Authors
Wenbo Tang
Matthew Kowgier
Daan W. Loth
Mar�a Soler Artigas
Bonnie R. Joubert
Emily Hodge
Sina A. Gharib
Albert V. Smith
Ingo Ruczinski
Vilmundur Gudnason
Rasika A. Mathias
Tamara B. Harris
Nadia N. Hansel
Lenore J. Launer
Kathleen C. Barnes
Joyanna G. Hansen
Eva Albrecht
Melinda C. Aldrich
Michael Allerhand
R. Graham Barr
Guy G. Brusselle
David J. Couper
Ivan Curjuric
Gail Davies
Ian J. Deary
Jos�e Dupuis
Tove Fall
Millennia Foy
Nora Franceschini
Wei Gao
Sven Gl�ser
Xiangjun Gu
Dana B. Hancock
Joachim Heinrich
Albert Hofman
Medea Imboden
Erik Ingelsson
Alan James
Stefan Karrasch
Beate Koch
Stephen B. Kritchevsky
Ashish Kumar
Lies Lahousse
Guo Li
Lars Lind
Cecilia Lindgren
Yongmei Liu
Kurt Lohman
Thomas Lumley
Wendy L. McArdle
Bernd Meibohm
Andrew P. Morris
Alanna C. Morrison
Bill Musk
Kari E. North
Lyle J. Palmer
Nicole M. Probst-Hensch
Bruce M. Psaty
Fernando Rivadeneira
Jerome I. Rotter
Holger Schulz
Lewis J. Smith
Akshay Sood
John M. Starr
David P. Strachan
Alexander Teumer
Andr� G. Uitterlinden
Henry V�lzke
Arend Voorman
Louise V. Wain
Martin T. Wells
Jemma B. Wilk
O. Dale Williams
Susan R. Heckbert
Bruno H. Stricker
Stephanie J. London
Myriam Fornage
Martin D. Tobin
George T. O?Connor
IAN HALL IAN.HALL@NOTTINGHAM.AC.UK
Professor of Molecular Medicine
Patricia A. Cassano
Contributors
Lin Chen
Editor
Abstract
Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function.
Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis.
Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 6 10-7). In addition, meta-analysis using the five cohorts with $3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18610-8) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively.
Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.
Citation
Chen, L., Tang, W., Kowgier, M., Loth, D. W., Soler Artigas, M., Joubert, B. R., …Cassano, P. A. (2014). Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function. PLoS ONE, 9(7), Article e100776. https://doi.org/10.1371/journal.pone.0100776
Journal Article Type | Article |
---|---|
Acceptance Date | Apr 17, 2014 |
Online Publication Date | Jul 1, 2014 |
Publication Date | Jul 1, 2014 |
Deposit Date | Jul 21, 2017 |
Publicly Available Date | Jul 21, 2017 |
Journal | PLoS ONE |
Electronic ISSN | 1932-6203 |
Publisher | Public Library of Science |
Peer Reviewed | Peer Reviewed |
Volume | 9 |
Issue | 7 |
Article Number | e100776 |
DOI | https://doi.org/10.1371/journal.pone.0100776 |
Public URL | https://nottingham-repository.worktribe.com/output/729415 |
Publisher URL | http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0100776 |
Contract Date | Jul 21, 2017 |
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