@article{3082046,
  abstract     = {{Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV1), and its ratio to forced vital capacity (FEV1/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 FEV1 and FEV1/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 PJMA = 5.00610211), HLA-DQB1 and HLA-DQA2 (smallest PJMA = 4.3561029), and KCNJ2 and SOX9 (smallest PJMA = 1.2861028) were associated with FEV1/FVC or FEV1 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.}},
  articleno    = {{e1003098}},
  author       = {{Hancock, Dana B and Soler Artigas, María and Gharib, Sina A and Henry, Amanda and Manichaikul, Ani and Ramasamy, Adaikalavan and Loth, Daan W and Imboden, Medea and Koch, Beate and McArdle, Wendy L and Smith, Albert V and Smolonska, Joanna and Sood, Akshay and Tang, Wenbo and Wilk, Jemma B and Zhai, Guangju and Zhao, Jing Hua and Aschard, Hugues and Burkart, Kristin M and Curjuric, Ivan and Eijgelsheim, Mark and Elliott, Paul and Gu, Xiangjun and Harris, Tamara B and Janson, Christer and Homuyth, Georg and Hysi, Pirro G and Liu, Jason Z and Loehr, Laura R and Lohman, Kurt and Loos, Ruth JF and Manning, Alisa K and Marciante, Kristin D and Obeidat, Ma'en and Postma, Dirkje S and Aldrich, Melinda C and Brusselle, Guy and Chen, Ting-hsu and Eiriksdottir, Gudny and Franceschini, Nora and Heinrich, Joachim and Rotter, Jerome I and Wijmenga, Cisca and Williams, O Dale and Bentley, Amy R and Hofman, Albert and Laurie, Cathy C and Lumley, Thomas and Morrison, Alanna C and Joubert, Bonnie R and Rivandeneiro, Fernando and Couper, David J and Kritchevsky, Stephen B and Liu, Yongmei and Wjst, Matthias and Wain, Louise V and Vonk, Judith M and Uitterlinden, André G and Rochat, Thierry and Rich, Stephen S and Psaty, Bruce M and O'Connor, George T and North, Kari E and Mirel, Daniel B and Meibohm, Bernd and Launer, Lenore J and Khaw, Kay-Tee and Hartikainen, Anna-Liisa and Hammond, Christopher J and Gläser, Sven and Marchini, Jonathan and Kraft, Peter and Wareham, Nicholas J and Völzke, Henry and Stricker, Bruno HC and Spector, Timothy D and Probst-Hensch, Nicole M and Jarvis, Deborah and Jarvelin, Marjo-Riitta and Heckbert, Susan R and Gudnason, Vilmundur and Boezen, H Marike and Barr, R Graham and Cassano, Patricia A and Strachan, David P and Fornage, Myriam and Hall, Ian P and Dupuis, Josée and Tobin, Martin D and London, Stephanie J}},
  issn         = {{1553-7390}},
  journal      = {{PLOS GENETICS}},
  keywords     = {{AIR-FLOW OBSTRUCTION,GENE-ENVIRONMENT INTERACTION,SMOOTH-MUSCLE-CELLS,CLASS-II ANTIGENS,BODY-MASS INDEX,LUNG-FUNCTION,FOLLOW-UP,RHEUMATOID-ARTHRITIS,SIGNALING CONTROLS,COMMON VARIANTS}},
  language     = {{eng}},
  number       = {{12}},
  pages        = {{13}},
  title        = {{Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function}},
  url          = {{http://doi.org/10.1371/journal.pgen.1003098}},
  volume       = {{8}},
  year         = {{2012}},
}

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