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Hancock, D.B.* ; Artigas, M.S.* ; Gharib, S.A.* ; Henry, A.* ; Manichaikul, A.* ; Ramasamy, A.* ; Loth, D.W.* ; Imboden, M.* ; Koch, B.* ; McArdle, W.L.* ; Smith, A.V.* ; Smolonska, J.* ; Sood, A.* ; Tang, W.* ; Wilk, J.B.* ; Zhai, G.* ; Zhao, J.H.* ; Aschard, H.* ; Burkart, K.M.* ; Curjuric, I.* ; Eijgelsheim, M.* ; Elliott, P.* ; Gu, X.* ; Harris, T.B.* ; Janson, C.* ; Homuth, G.* ; Hysi, P.G.* ; Liu, J.Z.* ; Loehr, L.R.* ; Lohman, K.* ; Loos, R.J.* ; Manning, A.K.* ; Marciante, K.D.* ; Obeidat, M.* ; Postma, D.S.* ; Aldrich, M.C.* ; Brusselle, G.G.* ; Chen, T.H.* ; Eiriksdottir, G.* ; Franceschini, N.* ; Heinrich, J. ; Rotter, J.I.* ; Wijmenga, C.* ; Williams, O.D.* ; Bentley, A.R.* ; Hofman, A.* ; Laurie, C.C.* ; Lumley, T.* ; Morrison, A.C.* ; Joubert, B.R.* ; Rivadeneira, F.* ; Couper, D.J.* ; Kritchevsky, S.B.* ; Liu, Y.* ; Wjst, M. ; Wain, L.V.* ; Vonk, J.M.* ; Uitterlinden, A.G.* ; Rochat, T.* ; Rich, S.S.* ; Psaty, B.M.* ; O'Connor, G.T.* ; North, K.E.* ; Mirel, D.B.* ; Meibohm, B.* ; Launer, L.J.* ; Khaw, K.T.* ; Hartikainen, A.L.* ; Hammond, C.J.* ; Gläser, S.* ; Marchini, J.* ; Kraft, P.* ; Wareham, N.J.* ; Völzke, H.* ; Stricker, B.H.* ; Spector, T.D.* ; Probst-Hensch, N.M.* ; Jarvis, D.* ; Jarvelin, M.R.* ; Heckbert, S.R.* ; Gudnason, V.* ; Boezen, H.M.* ; Barr, R.G.* ; Cassano, P.A.* ; Strachan, D.P.* ; Fornage, M.* ; Hall, I.P.* ; Dupuis, J.* ; Tobin, M.D.* ; London, S.J.*

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

PLoS Genet. 8:e1003098 (2013)
Publ. Version/Full Text Volltext DOI PMC
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Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene-environment Interaction ; Air-flow Obstruction ; Smooth-muscle-cells ; Class-ii Antigens ; Body-mass Index ; Rheumatoid-arthritis ; Signaling Controls ; Common Variants ; Lung-function ; Epic-norfolk
Language english
Publication Year 2013
Prepublished in Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 8, Issue: 12, Pages: , Article Number: e1003098 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Lung Health and Immunity (LHI)
POF-Topic(s) 30503 - Chronic Diseases of the Lung and Allergies
30202 - Environmental Health
Research field(s) Genetics and Epidemiology
Lung Research
PSP Element(s) G-503900-001
G-505000-003
PubMed ID 23284291
DOI 10.1371/journal.pgen.1003098
WOS ID WOS:000312905600013
Scopus ID 84872034012
Erfassungsdatum 2012-12-31
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