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Tang, W.* ; Kowgier, M.* ; Loth, D.W.* ; Soler Artigas, M.* ; Joubert, B.R.* ; Hodge, E.* ; Gharib, S.A.* ; Smith, A.V.* ; Ruczinski, I.* ; Gudnason, V.* ; Mathias, R.A.* ; Harris, T.B.* ; Hansel, N.N.* ; Launer, L.J.* ; Barnes, K.C.* ; Hansen, J.G.* ; Albrecht, E. ; Aldrich, M.C.* ; Allerhand, M.* ; Barr, R.G.* ; Brusselle, G.G.* ; Couper, D.J.* ; Curjuric, I.* ; Davies, G.* ; Deary, I.J.* ; Dupuis, J.* ; Fall, T.* ; Foy, M.* ; Franceschini, N.* ; Gao, W.* ; Gläser, S.* ; Gu, X.* ; Hancock, D.B.* ; Heinrich, J. ; Hofman, A.* ; Imboden, M.* ; Ingelsson, E.* ; James, A.* ; Karrasch, S. ; Koch, B.* ; Kritchevsky, S.B.* ; Kumar, A.* ; Lahousse, L.* ; Li, G.* ; Lind, L.* ; Lindgren, C.* ; Liu, Y.* ; Lohman, K.* ; Lumley, T.* ; McArdle, W.L.* ; Meibohm, B.* ; Morris, A.P.* ; Morrison, A.C.* ; Musk, B.* ; North, K.E.* ; Palmer, L.J.* ; Probst-Hensch, N.M.* ; Psaty, B.M.* ; Rivadeneira, F.* ; Rotter, J.I.* ; Schulz, H. ; Smith, L.J.* ; Sood, A.* ; Starr, J.M.* ; Strachan, D.P.* ; Teumer, A.* ; Uitterlinden, A.G.* ; Völzke, H.* ; Voorman, A.* ; Wain, L.V.* ; Wells, M.T.* ; Wilk, J.B.* ; Williams, O.D.* ; Heckbert, S.R.* ; Stricker, B.H.* ; London, S.J.* ; Fornage, M.* ; Tobin, M.D.* ; O'Connor, G.T.* ; Hall, I.P.* ; Cassano, P.A.*

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

PLoS ONE 9:e100776 (2014)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 × 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Obstructive Pulmonary-disease; Epidermodysplasia-verruciformis; Function Decline; Global Burden; Malic Enzyme; Hearing-loss; Asthma; Expression; Gene; Interleukin-16
Sprache englisch
Veröffentlichungsjahr 2014
HGF-Berichtsjahr 2014
ISSN (print) / ISBN 1932-6203
Zeitschrift PLoS ONE
Quellenangaben Band: 9, Heft: 7, Seiten: , Artikelnummer: e100776 Supplement: ,
Verlag Public Library of Science (PLoS)
Verlagsort Lawrence, Kan.
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504100-001
G-503900-003
G-503900-001
PubMed ID 24983941
DOI 10.1371/journal.pone.0100776
WOS ID WOS:000339635000039
Scopus ID 84903736975
Erfassungsdatum 2014-07-03
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