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; Smith, Albert Vernon; 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; Zhao, Jing Hua; de Jong, Kim; Lyytikäinen, Leo-Pekka; Wain, Louise V; Järvelin, 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; Understanding Society Scientific Group; Jackson, Victoria E; Gudnason, Vilmundur; Tang, Wenbo; Dupuis, Josée; Artigas, María Soler; Joshi, Amit D; London, Stephanie J; Kraft, Peter (2017-01-12)
Hugues Aschard, Martin D Tobin, Dana B Hancock, David Skurnik, Akshay Sood, Alan James, Albert Vernon Smith, Ani W Manichaikul, Archie Campbell, Bram P Prins, Caroline Hayward, Daan W Loth, David J Porteous, David P Strachan, Eleftheria Zeggini, George T O’Connor, Guy G Brusselle, H Marike Boezen, Holger Schulz, Ian J Deary, Ian P Hall, Igor Rudan, Jaakko Kaprio, James F Wilson, Jemma B Wilk, Jennifer E Huffman, Jing Hua Zhao, Kim de Jong, Leo-Pekka Lyytikäinen, Louise V Wain, Marjo-Riitta Jarvelin, Mika Kähönen, Myriam Fornage, Ozren Polasek, Patricia A Cassano, R Graham Barr, Rajesh Rawal, Sarah E Harris, Sina A Gharib, Stefan Enroth, Susan R Heckbert, Terho Lehtimäki, Ulf Gyllensten, Understanding Society Scientific Group, Victoria E Jackson, Vilmundur Gudnason, Wenbo Tang, Josée Dupuis, María Soler Artigas, Amit D Joshi, Stephanie J London, Peter Kraft; Evidence for large-scale gene-by-smoking interaction effects on pulmonary function, International Journal of Epidemiology, Volume 46, Issue 3, 1 June 2017, Pages 894–904, https://doi.org/10.1093/ije/dyw318
© The Author 2017. Published by Oxford University Press on behalf of the International Epidemiological Association This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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 (βint = −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.
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