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Evidence for large-scale gene-by-smoking interaction effects on pulmonary function

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Abstract
Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. Results: We identified an interaction (beta(int) = -0.036, 95% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.
Keywords
GENOME-WIDE ASSOCIATION, ENVIRONMENT INTERACTIONS, LUNG-FUNCTION, RISK, EPIDEMIOLOGY, OPPORTUNITIES, OBSTRUCTION, PREDICTION, FEV1/FVC, DISEASE, FEV1/FVC, smoking, gene-environment interaction, genetic risk score

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Chicago
Aschard, Hugues, Martin D Tobin, Dana B Hancock, David Skurnik, Akshay Sood, Alan James, Albert Vernon Smith, et al. 2017. “Evidence for Large-scale Gene-by-smoking Interaction Effects on Pulmonary Function.” International Journal of Epidemiology 46 (3): 894–904.
APA
Aschard, H., Tobin, M. D., Hancock, D. B., Skurnik, D., Sood, A., James, A., Smith, A. V., et al. (2017). Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 46(3), 894–904.
Vancouver
1.
Aschard H, Tobin MD, Hancock DB, Skurnik D, Sood A, James A, et al. Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. INTERNATIONAL JOURNAL OF EPIDEMIOLOGY. 2017;46(3):894–904.
MLA
Aschard, Hugues, Martin D Tobin, Dana B Hancock, et al. “Evidence for Large-scale Gene-by-smoking Interaction Effects on Pulmonary Function.” INTERNATIONAL JOURNAL OF EPIDEMIOLOGY 46.3 (2017): 894–904. Print.
@article{8537617,
  abstract     = {Background: Smoking is the strongest environmental risk factor for reduced pulmonary function. The genetic component of various pulmonary traits has also been demonstrated, and at least 26 loci have been reproducibly associated with either FEV1 (forced expiratory volume in 1 second) or FEV1/FVC (FEV1/forced vital capacity). Although the main effects of smoking and genetic loci are well established, the question of potential gene-by-smoking interaction effect remains unanswered. The aim of the present study was to assess, using a genetic risk score approach, whether the effect of these 26 loci on pulmonary function is influenced by smoking. 
Methods: We evaluated the interaction between smoking exposure, considered as either ever vs never or pack-years, and a 26-single nucleotide polymorphisms (SNPs) genetic risk score in relation to FEV1 or FEV1/FVC in 50 047 participants of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) and SpiroMeta consortia. 
Results: We identified an interaction (beta(int) = -0.036, 95\% confidence interval, -0.040 to -0.032, P = 0.00057) between an unweighted 26 SNP genetic risk score and smoking status (ever/never) on the FEV1/FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV1/FVC threshold used to diagnose chronic obstructive pulmonary disease is higher among ever smokers than among never smokers. A replication analysis in two independent datasets, although not statistically significant, showed a similar trend in the interaction effect. 
Conclusions: This study highlights the benefit of using genetic risk scores for identifying interactions missed when studying individual SNPs and shows, for the first time, that persons with the highest genetic risk for low FEV1/FVC may be more susceptible to the deleterious effects of smoking.},
  author       = {Aschard, Hugues and Tobin, Martin D and Hancock, Dana B and Skurnik, David and Sood, Akshay and James, Alan and Smith, Albert Vernon and Manichaikul, Aniw and Campbell, Archie and Prins, Bram P and Hayward, Caroline and Loth, Daanw and Porteous, David J and Strachan, David P and Zeggini, Eleftheria and O'Connor, George T and Brusselle, Guy and Boezen, H Marike and Schulz, Holger and Deary, Ian J and Hall, Ian P and Rudan, Igor and Kaprio, Jaakko and Wilson, James F and Wilk, Jemma B and Huffman, Jennifer E and Zhao, Jing Hua and de Jong, Kim and Lyytikainen, Leo-Pekka and Wain, Louise V and Jarvelin, Marjo-Riitta and Kahonen, Mika and Fornage, Myriam and Polasek, Ozren and Cassano, Patricia A and Barr, R Graham and Rawal, Rajesh and Harris, Sarah E and Gharib, Sina A and Enroth, Stefan and Heckbert, Susan R and Lehtimaki, Terho and Gyllensten, Ulf and Jackson, Victoria E and Gudnason, Vilmundur and Tang, Wenbo and Dupuis, Josee and Artigas, Maria Soler and Joshi, Amit D and London, Stephanie J and Kraft, Peter},
  issn         = {0300-5771},
  journal      = {INTERNATIONAL JOURNAL OF EPIDEMIOLOGY},
  language     = {eng},
  number       = {3},
  pages        = {894--904},
  title        = {Evidence for large-scale gene-by-smoking interaction effects on pulmonary function},
  url          = {http://dx.doi.org/10.1093/ije/dyw318},
  volume       = {46},
  year         = {2017},
}

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