Evidence for large-scale gene-by-smoking interaction effects on pulmonary function
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 (FEV...
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| Format: | Article |
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Oxford University Press
2017
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| Online Access: | https://eprints.nottingham.ac.uk/44358/ |
| _version_ | 1848796898558738432 |
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| author | Aschard, Hugues Tobin, Martin D. Hancock, Dana B. Skurnik, David Sood, Akshay James, Alan Vernon Smith, Albert Manichaikul, Ani W. Campbell, Archie Prins, Bram P. Hayward, Caroline Loth, Daan W. Porteous, David J. Strachan, David P. Zeggini, Eleftheria O’Connor, George T. Brusselle, Guy G. Boezen, H. Marike Schulz, Holger Deary, Ian J. Hall, Ian P. Rudan, Igor Kaprio, Jaakko Wilson, James F. Wilk, Jemma B. Huffman, Jennifer E. Hua Zhao, Jing de Jong, Kim Lyytikäinen, Leo-Pekka Wain, Louise V. Jarvelin, Marjo-Riitta Kähönen, Mika Fornage, Myriam Polasek, Ozren Cassano, Patricia A. Barr, R. Graham Rawal, Rajesh Harris, Sarah E. Gharib, Sina A. Enroth, Stefan Heckbert, Susan R. Lehtimäki, Terho Gyllensten, Ulf Gudnason, Vilmundur Jackson, Victoria E. Tang, Wenbo Dupuis, Josée Soler Artigas, María Joshi, Amit D. London, Stephanie J. Kraft, Peter |
| author_facet | Aschard, Hugues Tobin, Martin D. Hancock, Dana B. Skurnik, David Sood, Akshay James, Alan Vernon Smith, Albert Manichaikul, Ani W. Campbell, Archie Prins, Bram P. Hayward, Caroline Loth, Daan W. Porteous, David J. Strachan, David P. Zeggini, Eleftheria O’Connor, George T. Brusselle, Guy G. Boezen, H. Marike Schulz, Holger Deary, Ian J. Hall, Ian P. Rudan, Igor Kaprio, Jaakko Wilson, James F. Wilk, Jemma B. Huffman, Jennifer E. Hua Zhao, Jing de Jong, Kim Lyytikäinen, Leo-Pekka Wain, Louise V. Jarvelin, Marjo-Riitta Kähönen, Mika Fornage, Myriam Polasek, Ozren Cassano, Patricia A. Barr, R. Graham Rawal, Rajesh Harris, Sarah E. Gharib, Sina A. Enroth, Stefan Heckbert, Susan R. Lehtimäki, Terho Gyllensten, Ulf Gudnason, Vilmundur Jackson, Victoria E. Tang, Wenbo Dupuis, Josée Soler Artigas, María Joshi, Amit D. London, Stephanie J. Kraft, Peter |
| author_sort | Aschard, Hugues |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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 (bint=–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. |
| first_indexed | 2025-11-14T19:55:18Z |
| format | Article |
| id | nottingham-44358 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:55:18Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-443582020-05-04T18:30:53Z https://eprints.nottingham.ac.uk/44358/ Evidence for large-scale gene-by-smoking interaction effects on pulmonary function Aschard, Hugues Tobin, Martin D. Hancock, Dana B. Skurnik, David Sood, Akshay James, Alan Vernon Smith, Albert Manichaikul, Ani W. Campbell, Archie Prins, Bram P. Hayward, Caroline Loth, Daan W. Porteous, David J. Strachan, David P. Zeggini, Eleftheria O’Connor, George T. Brusselle, Guy G. Boezen, H. Marike Schulz, Holger Deary, Ian J. Hall, Ian P. Rudan, Igor Kaprio, Jaakko Wilson, James F. Wilk, Jemma B. Huffman, Jennifer E. Hua Zhao, Jing de Jong, Kim Lyytikäinen, Leo-Pekka Wain, Louise V. Jarvelin, Marjo-Riitta Kähönen, Mika Fornage, Myriam Polasek, Ozren Cassano, Patricia A. Barr, R. Graham Rawal, Rajesh Harris, Sarah E. Gharib, Sina A. Enroth, Stefan Heckbert, Susan R. Lehtimäki, Terho Gyllensten, Ulf Gudnason, Vilmundur Jackson, Victoria E. Tang, Wenbo Dupuis, Josée Soler Artigas, María Joshi, Amit D. London, Stephanie J. Kraft, Peter 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 (bint=–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. Oxford University Press 2017-01-12 Article PeerReviewed Aschard, Hugues, Tobin, Martin D., Hancock, Dana B., Skurnik, David, Sood, Akshay, James, Alan, Vernon Smith, Albert, Manichaikul, Ani W., Campbell, Archie, Prins, Bram P., Hayward, Caroline, Loth, Daan W., Porteous, David J., Strachan, David P., Zeggini, Eleftheria, O’Connor, George T., Brusselle, Guy G., Boezen, H. Marike, Schulz, Holger, Deary, Ian J., Hall, Ian P., Rudan, Igor, Kaprio, Jaakko, Wilson, James F., Wilk, Jemma B., Huffman, Jennifer E., Hua Zhao, Jing, de Jong, Kim, Lyytikäinen, Leo-Pekka, Wain, Louise V., Jarvelin, Marjo-Riitta, Kähönen, Mika, Fornage, Myriam, Polasek, Ozren, Cassano, Patricia A., Barr, R. Graham, Rawal, Rajesh, Harris, Sarah E., Gharib, Sina A., Enroth, Stefan, Heckbert, Susan R., Lehtimäki, Terho, Gyllensten, Ulf, Gudnason, Vilmundur, Jackson, Victoria E., Tang, Wenbo, Dupuis, Josée, Soler Artigas, María, Joshi, Amit D., London, Stephanie J. and Kraft, Peter (2017) Evidence for large-scale gene-by-smoking interaction effects on pulmonary function. International Journal of Epidemiology . dyw318. ISSN 0300-5771 https://academic.oup.com/ije/article-lookup/doi/10.1093/ije/dyw318 doi:10.1093/ije/dyw318 doi:10.1093/ije/dyw318 |
| spellingShingle | Aschard, Hugues Tobin, Martin D. Hancock, Dana B. Skurnik, David Sood, Akshay James, Alan Vernon Smith, Albert Manichaikul, Ani W. Campbell, Archie Prins, Bram P. Hayward, Caroline Loth, Daan W. Porteous, David J. Strachan, David P. Zeggini, Eleftheria O’Connor, George T. Brusselle, Guy G. Boezen, H. Marike Schulz, Holger Deary, Ian J. Hall, Ian P. Rudan, Igor Kaprio, Jaakko Wilson, James F. Wilk, Jemma B. Huffman, Jennifer E. Hua Zhao, Jing de Jong, Kim Lyytikäinen, Leo-Pekka Wain, Louise V. Jarvelin, Marjo-Riitta Kähönen, Mika Fornage, Myriam Polasek, Ozren Cassano, Patricia A. Barr, R. Graham Rawal, Rajesh Harris, Sarah E. Gharib, Sina A. Enroth, Stefan Heckbert, Susan R. Lehtimäki, Terho Gyllensten, Ulf Gudnason, Vilmundur Jackson, Victoria E. Tang, Wenbo Dupuis, Josée Soler Artigas, María Joshi, Amit D. London, Stephanie J. Kraft, Peter Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title | Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title_full | Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title_fullStr | Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title_full_unstemmed | Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title_short | Evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| title_sort | evidence for large-scale gene-by-smoking interaction effects on pulmonary function |
| url | https://eprints.nottingham.ac.uk/44358/ https://eprints.nottingham.ac.uk/44358/ https://eprints.nottingham.ac.uk/44358/ |