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Evaluation of Respiratory System Mechanics in Mice using the Forced Oscillation Technique
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Evidence for large-scale gene-by-smoking interaction effects on pulmonary function.

Hugues Aschard1,2, Martin D Tobin3,4, Dana B Hancock5

  • 1Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.

International Journal of Epidemiology
|January 14, 2017
PubMed
Summary

This study found that a genetic risk score combined with smoking status significantly impacts pulmonary function, specifically the FEV 1 /FVC ratio. Individuals with a higher genetic predisposition to low FEV 1 /FVC are more vulnerable to smoking

Keywords:
FEV1/FVCgenetic risk scoregene–environment interactionsmoking

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Area of Science:

  • Genomics
  • Pulmonary Medicine
  • Environmental Health

Background:

  • Smoking is a primary environmental risk for reduced pulmonary function.
  • Genetic factors also influence pulmonary traits, with 26 loci linked to FEV 1 or FEV 1 /FVC.
  • Gene-by-smoking interactions on pulmonary function remain largely unexplored.

Purpose of the Study:

  • To investigate if genetic loci associated with pulmonary function are influenced by smoking.
  • To assess gene-by-smoking interactions using a genetic risk score approach.

Main Methods:

  • Evaluated the interaction between smoking exposure (ever/never, pack-years) and a 26-SNP genetic risk score.
  • Analyzed FEV 1 and FEV 1 /FVC in 50,047 European ancestry participants from CHARGE and SpiroMeta consortia.

Main Results:

  • Identified a significant interaction between the 26-SNP genetic risk score and smoking status (ever/never) on the FEV 1 /FVC ratio.
  • The genetic risk for low FEV 1 /FVC, indicative of COPD, is elevated in ever smokers compared to never smokers.
  • Replication analyses showed a consistent trend, though not statistically significant.

Conclusions:

  • Genetic risk scores are valuable for detecting interactions missed by single SNP analyses.
  • This study demonstrates that individuals with high genetic risk for low FEV 1 /FVC are more susceptible to smoking's adverse effects.
  • Highlights the interplay between genetics and environmental factors in determining pulmonary health.