Trial reportThorax2011
Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies.
Trial report in Thorax, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Assessing the social and physical determinants of circumpolar population health.International journal of circumpolar health · 2013Pooled it
- Quantitative analysis of chest computed tomography in alpha-1-antitrypsin deficiency.Respiratory research · 2025Article
- Genetic resilience to chronic obstructive pulmonary disease is a clinically distinct subtype in individuals with cigarette smoke exposure.Respiratory research · 2025Article
- Recent advancements in understanding the genetic involvement of alpha-1 antitrypsin deficiency associated lung disease: a look at future precision medicine approaches.Expert review of respiratory medicine · 2022Review
- Alternative poly-adenylation modulates α1-antitrypsin expression in chronic obstructive pulmonary disease.PLoS genetics · 2021Article
- Genome-Wide Gene-by-Smoking Interaction Study of Chronic Obstructive Pulmonary Disease.American journal of epidemiology · 2021Article
- Effect of 6p21 region on lung function is modified by smoking: a genome-wide interaction study.Scientific reports · 2020Article
- Defining a role for lung function associated gene GSTCD in cell homeostasis.Respiratory research · 2019Article
- Genome-wide assessment of gene-by-smoking interactions in COPD.Scientific reports · 2018Article
- Established and Emerging Environmental Contributors to Disparities in Asthma and Chronic Obstructive Pulmonary Disease.Current epidemiology reports · 2018Article
- Proportion and clinical characteristics of non-asthmatic non-smokers among adults with airflow obstruction.PloS one · 2018Article
- Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.EBioMedicine · 2016Article
- Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene-environment interactions.Journal of human genetics · 2015Article
- Clinical applications of gene-based risk prediction for lung cancer and the central role of chronic obstructive pulmonary disease.Frontiers in genetics · 2012Article
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 6 countries.
Funding
Abstract
backgroundThe identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV(1)); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity.
methodsThe relationship between FEV(1) and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects.
resultsNon-linear relationships between smoking and FEV(1) were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV(1) is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case-Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV(1) analysis, p=0.01 for COPD susceptibility analysis).
conclusionIn study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV(1) is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.