ArticleInternational journal of epidemiology2017
Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.
Article in International journal of epidemiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 55 citations in OpenAlex.
- Interaction between Genetic Risk Scores for reduced pulmonary function and smoking, asthma and endotoxin.Thorax · 2021Pooled it
- New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries.Nature genetics · 2019Pooled it
- Genome-Wide Association Study of Plasma Sodium Concentrations with and without Exposure to Thiazide Diuretics.Journal of the American Society of Nephrology : JASN · 2025Article
- Article
- Tradeoffs in Modeling Context Dependency in Complex Trait Genetics.bioRxiv : the preprint server for biology · 2025Article
- Accounting for genetic effect heterogeneity in fine-mapping and improving power to detect gene-environment interactions with SharePro.Nature communications · 2024Article
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities.American journal of respiratory and critical care medicine · 2023Article
- Multi-omic association study identifies DNA methylation-mediated genotype and smoking exposure effects on lung function in children living in urban settings.PLoS genetics · 2023Article
- A robust and adaptive framework for interaction testing in quantitative traits between multiple genetic loci and exposure variables.PLoS genetics · 2022Article
- Gene-lifestyle interactions in the genomics of human complex traits.European journal of human genetics : EJHG · 2022Article
- Genetics of chronic obstructive pulmonary disease: understanding the pathobiology and heterogeneity of a complex disorder.The Lancet. Respiratory medicine · 2022Review
- Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals.Environment international · 2022Article
- Interaction of Cigarette Smoking and Polygenic Risk Score on Reduced Lung Function.JAMA network open · 2021Observational
- A polygenic-score-based approach for identification of gene-drug interactions stratifying breast cancer risk.American journal of human genetics · 2021Article
- Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.American journal of epidemiology · 2021Article
- Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants.Nature communications · 2020Article
- Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study.Scientific reports · 2020Article
- Why is Disease Penetration So Variable? Role of Genetic Modifiers of Lung Function in Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
- Genetic susceptibility to asthma increases the vulnerability to indoor air pollution.The European respiratory journal · 2020Article
Corrections and comments
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Authors and funding
52 authors at 20 institutions in 10 countries.
Funding
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 FEV 1 (forced expiratory volume in 1 second) or FEV 1 /FVC (FEV 1 /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 FEV 1 or FEV 1 /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 FEV 1 /FVC ratio. In interpreting this interaction, we showed that the genetic risk of falling below the FEV /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 FEV 1 /FVC may be more susceptible to the deleterious effects of smoking.
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