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Title: Genome-Wide Joint Meta-Analysis of SNP and SNP-by-Smoking Interaction Identifies Novel Loci for Pulmonary Function
Authors: Hancock, Dana B.;Artigas, María Soler;Gharib, Sina A.;Henry, Amanda;Manichaikul, Ani;Ramasamy, Adaikalavan;Loth, Daan W.;Imboden, Medea;Koch, Beate;McArdle, Wendy L.;Smith, Albert V.;Smolonska, Joanna;Sood, Akshay;Tang, Wenbo;Zhai, Guangju;Burkart, Kristin M.;Curjuric, Ivan;Eijgelsheim, Mark;Elliott, Paul;Gu, Xiangjun;Harris, Tamara B.;Janson, Christer;Homuth, Georg;Hysi, Pirro G.;Loehr, Laura R.;Lohman, Kurt;Loos, Ruth J. F.;Marciante, Kristin D.;Obeidat, Ma'en;Postma, Dirkje S.;Aldrich, Melinda C.;Brusselle, Guy G.;Eiriksdottir, Gudny;Franceschini, Nora;Heinrich, Joachim;Rotter, Jerome I.;Wijmenga, Cisca;Bentley, Amy R.;Laurie, Cathy C.;Lumley, Thomas;Morrison, Alanna C.;Joubert, Bonnie R.;Rivadeneira, Fernando;Couper, David J.;Kritchevsky, Stephen B.;Liu, Yongmei;Wjst, Matthias;Wain, Louise V.;Vonk, Judith M.;Uitterlinden, André G.;Rochat, Thierry;Rich, Stephen S.;Psaty, Bruce M.;O'Connor, George T.;North, Kari E.;Mirel, Daniel B.;Meibohm, Bernd;Launer, Lenore J.;Khaw, Kay-Tee;Hartikainen, Anna-Liisa;Hammond, Christopher J.;Gläser, Sven;Marchini, Jonathan;Wareham, Nicholas J.;Völzke, Henry;Stricker, Bruno H. C.;Spector, Timothy D.;Probst-Hensch, Nicole M.;Jarvis, Deborah;Jarvelin, Marjo-Riitta;Heckbert, Susan R.;Gudnason, Vilmundur;Boezen, H. Marike;Barr, R. Graham;Cassano, Patricia A.;Strachan, David P.;Fornage, Myriam;Hall, Ian P.;Dupuis, Josée;Tobin, Martin D.;London, Stephanie J.;Wilk, Jemma B;Zhao, Jing Hua;Aschard, Hugues;Liu, Jason Z.;Manning, Alisa K;Chen, Ting-Hsu;Williams, O. Dale;Kraft, Phillip L.;Hofman, Albert
subject: Biology;Genetics;Human Genetics;Genetic Association Studies;Genome-Wide Association Studies;Genetics of Disease;Genomics;Genome Analysis Tools;Genome Scans;Medicine;Epidemiology;Genetic Epidemiology;Public Health;Environmental Health;Pulmonology;Smoking Related Disorders
Year: 2012
Publisher: Public Library of Science
Description: 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.
Standard no: Hancock, Dana B., María Soler Artigas, Sina A. Gharib, Amanda Henry, Ani Manichaikul, Adaikalavan Ramasamy, Daan W. Loth, et al. 2012. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genetics 8(12): e1003098.
Appears in Collections:HSPH Scholarly Articles

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