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

Publication ,  Journal Article
Hancock, DB; Soler Artigas, M; Gharib, SA; Henry, A; Manichaikul, A; Ramasamy, A; Loth, DW; Imboden, M; Koch, B; McArdle, WL; Smith, AV; Gu, X ...
Published in: PLoS Genet
2012

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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Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

12

Start / End Page

e1003098

Location

United States

Related Subject Headings

  • Vital Capacity
  • Smoking
  • SOX9 Transcription Factor
  • Receptors, Cell Surface
  • Pulmonary Disease, Chronic Obstructive
  • Potassium Channels, Inwardly Rectifying
  • Polymorphism, Single Nucleotide
  • Nerve Tissue Proteins
  • Lung
  • Humans
 

Citation

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Hancock, D. B., Soler Artigas, M., Gharib, S. A., Henry, A., Manichaikul, A., Ramasamy, A., … London, S. J. (2012). Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genet, 8(12), e1003098. https://doi.org/10.1371/journal.pgen.1003098
Hancock, Dana B., María Soler Artigas, Sina A. Gharib, Amanda Henry, Ani Manichaikul, Adaikalavan Ramasamy, Daan W. Loth, et al. “Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.PLoS Genet 8, no. 12 (2012): e1003098. https://doi.org/10.1371/journal.pgen.1003098.
Hancock DB, Soler Artigas M, Gharib SA, Henry A, Manichaikul A, Ramasamy A, et al. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genet. 2012;8(12):e1003098.
Hancock, Dana B., et al. “Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.PLoS Genet, vol. 8, no. 12, 2012, p. e1003098. Pubmed, doi:10.1371/journal.pgen.1003098.
Hancock DB, Soler Artigas M, Gharib SA, Henry A, Manichaikul A, Ramasamy A, Loth DW, Imboden M, Koch B, McArdle WL, Smith AV, Smolonska J, Sood A, Tang W, Wilk JB, Zhai G, Zhao JH, Aschard H, Burkart KM, Curjuric I, Eijgelsheim M, Elliott P, Gu X, Harris TB, Janson C, Homuth G, Hysi PG, Liu JZ, Loehr LR, Lohman K, Loos RJF, Manning AK, Marciante KD, Obeidat M, Postma DS, Aldrich MC, Brusselle GG, Chen T-H, Eiriksdottir G, Franceschini N, Heinrich J, Rotter JI, Wijmenga C, Williams OD, Bentley AR, Hofman A, Laurie CC, Lumley T, Morrison AC, Joubert BR, Rivadeneira F, Couper DJ, Kritchevsky SB, Liu Y, Wjst M, Wain LV, Vonk JM, Uitterlinden AG, Rochat T, Rich SS, Psaty BM, O’Connor GT, North KE, Mirel DB, Meibohm B, Launer LJ, Khaw K-T, Hartikainen A-L, Hammond CJ, Gläser S, Marchini J, Kraft P, Wareham NJ, Völzke H, Stricker BHC, Spector TD, Probst-Hensch NM, Jarvis D, Jarvelin M-R, Heckbert SR, Gudnason V, Boezen HM, Barr RG, Cassano PA, Strachan DP, Fornage M, Hall IP, Dupuis J, Tobin MD, London SJ. Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function. PLoS Genet. 2012;8(12):e1003098.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

2012

Volume

8

Issue

12

Start / End Page

e1003098

Location

United States

Related Subject Headings

  • Vital Capacity
  • Smoking
  • SOX9 Transcription Factor
  • Receptors, Cell Surface
  • Pulmonary Disease, Chronic Obstructive
  • Potassium Channels, Inwardly Rectifying
  • Polymorphism, Single Nucleotide
  • Nerve Tissue Proteins
  • Lung
  • Humans