@article{24239b1286d549988edb4dae7ecf8c26,
title = "Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function",
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 (FEV 1) 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 × 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 = 2.18 × 10-8) 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.",
author = "Wenbo Tang and Matthew Kowgier and Loth, {Daan W.} and {Soler Artigas}, Mar{\'i}a and Joubert, {Bonnie R.} and Emily Hodge and Gharib, {Sina A.} and Smith, {Albert V.} and Ingo Ruczinski and Vilmundur Gudnason and Mathias, {Rasika A.} and Harris, {Tamara B.} and Hansel, {Nadia N.} and Launer, {Lenore J.} and Barnes, {Kathleen C.} and Hansen, {Joyanna G.} and Eva Albrecht and Aldrich, {Melinda C.} and Michael Allerhand and Barr, {R. Graham} and Brusselle, {Guy G.} and Couper, {David J.} and Ivan Curjuric and Gail Davies and Deary, {Ian J.} and Jos{\'e}e Dupuis and Tove Fall and Millennia Foy and Nora Franceschini and Wei Gao and Sven Gl{\"a}ser and Xiangjun Gu and Hancock, {Dana B.} and Joachim Heinrich and Albert Hofman and Medea Imboden and Erik Ingelsson and Alan James and Stefan Karrasch and Beate Koch and Kritchevsky, {Stephen B.} and Ashish Kumar and Lies Lahousse and Guo Li and Lars Lind and Cecilia Lindgren and Yongmei Liu and Kurt Lohman and Thomas Lumley and McArdle, {Wendy L.} and Bernd Meibohm and Morris, {Andrew P.} and Morrison, {Alanna C.} and Bill Musk and North, {Kari E.} and Palmer, {Lyle J.} and Probst-Hensch, {Nicole M.} and Psaty, {Bruce M.} and Fernando Rivadeneira and Rotter, {Jerome I.} and Holger Schulz and Smith, {Lewis J.} and Akshay Sood and Starr, {John M.} and Strachan, {David P.} and Alexander Teumer and Uitterlinden, {Andr{\'e} G.} and Henry V{\"o}lzke and Arend Voorman and Wain, {Louise V.} and Wells, {Martin T.} and Wilk, {Jemma B.} and Williams, {O. Dale} and Heckbert, {Susan R.} and Stricker, {Bruno H.} and London, {Stephanie J.} and Myriam Fornage and Tobin, {Martin D.} and O'Connor, {George T.} and Hall, {Ian P.} and Cassano, {Patricia A.}",
note = "Funding Information: All authors have read the journal's policy, and 57 of the 81 authors have declared that no competing interests exist. The following 24 authors have possible conflicts, as follows: Dr. Aldrich reports grants from NIH, during the conduct of the study; Dr. Barnes reports grants from NIH, during the conduct of the study; Dr. Barr reports grants from NIH and US—EPA, during the conduct of the study; Dr. Couper reports grants from NIH, during the conduct of the study; Dr. Deary reports grants from Age UK, grants from BBSRC, during the conduct of the study; Dr. Dupuis reports grants from Boston University, during the conduct of the study; Dr. Fall reports personal fees from MSD (Merck), outside the submitted work; Dr. Gudnason reports other from NIH, during the conduct of the study; Dr. Gl{\"a}ser reports grants from BMBF (German Ministry for Research and Education), during the conduct of the study; personal fees from Actelion Pharma, personal fees from Novartis Pharma, personal fees from GSK, personal fees from Pfizer, personal fees from Boehringer Ingelheim, personal fees from Bayer Pharma, all those apply outside of the submitted work; Dr. Hall reports grants received from MRC and Pfizer, and Vertex sponsored lecture at ERS, outside the submitted work; Dr. Hodge reports grants from The Medical Research Council, UK, during the conduct of the study; Dr. Koch reports grants from BMBF, during the conduct of the study, travel fees from Actelion Pharma, Pfizer, Bayer Pharma, the German Academic Exchange Service, and the Research Network for Community Medicine of the University of Greifswald, one research prize of the Society of Internal Medicine Mecklenburg-Vorpommern, Germany, outside the submitted work; Dr. Lahousse reports grant from Belgian Society of Pneumology, during the conduct of the study; Dr. London is funded in full by the Division of Intramural Research, NIEHS, NIH, DHHS; Dr. Lumley reports grants from NIH, during the conduct of the study; Dr. Mathias reports grants from NIH, during the conduct of the study; Dr. Meibohm reports grants from NIH, during the conduct of the study; Dr. O'Connor reports personal fees from Sunovion, Inc., outside the submitted work; Dr. Psaty reports grants from NIH, during the conduct of the study, and Dr. Psaty serves on the DSMB for a clinical trial of a device, which is funded by the manufacturer (Zoll LifeCor), and he is on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson; Dr. L Smith reports personal fees as member of Merck Data Safety and Monitoring Board, outside the submitted work; Dr. Tobin reports grants from Medical Research Council grant G0902313, grants from National Institute for Health Research (NIHR), Leicester Respiratory Biomedical Research Unit, during the conduct of the study (the views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health), grants from Pfizer for collaborative research project (on rare sequence variants and the smoking resistant lung, Nov. 2010 to Nov 2012), outside the submitted work; Dr. Wain reports grants from Pfizer collaborative research project (onrare sequence variants and the smoking resistant lung, Nov. 2010 to Nov 2012), outside the submitted work; Dr. Wilk reports grants from FAMRI, grants from NIH, during the conduct of the study; personal fees from Pfizer, outside the submitted work. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials. ",
year = "2014",
month = jul,
day = "1",
doi = "10.1371/journal.pone.0100776",
language = "English (US)",
volume = "9",
journal = "PloS one",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",
}