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First published online on November 7, 2007
Chest, doi:10.1378/chest.07-1438
doi:10.1378/chest.07-1438
(Chest. 2007; 132:1772-1777)
© 2007 American College of Chest Physicians
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The Interaction of Genes and Smoking on Forced Expiratory Volume*

A Classic Twin Study

Guangju Zhai, PhD; Ana M. Valdes, PhD; Lynn Cherkas, PhD; Gail Clement, RGN; David Strachan, MD and Tim D. Spector, MD

* From the Twin Research & Genetic Epidemiology Unit (Drs. Zhai, Valdes, Cherkas, and Spector, and Ms. Clement), King’s College London School of Medicine; and Division of Community Health Sciences (Dr. Strachan), St George’s, University of London, London, UK.

Correspondence to: Guangju Zhai, PhD, Twin Research & Genetic Epidemiology Unit, King’s College London School of Medicine, St Thomas’ Hospital Campus, Lambeth Palace Rd, London SE1 7EH, UK; e-mail: guangju.zhai{at}kcl.ac.uk

Abstract

Background: Genetic influences on lung function as measured by FEV1 have been reported from twin and family studies. The aims of this study were to estimate heritability of the ratio of measured FEV1 (mFEV1) to expected FEV1 (eFEV1) in a white population, and to examine the interaction between genetic factors and smoking on this ratio.

Methods and subjects: The sample consisted of unselected monozygotic (MZ) and dizygotic (DZ) twin pairs from the TwinsUK registry. FEV1 was measured with a spirometer, and mFEV1/eFEV1 ratio was calculated.

Results: A total of 475 MZ and 1,054 DZ twin pairs participated (mean age, 47 years; range, 18 to 84 years). mFEV1/eFEV1 ratio was 0.057 lower in smokers than nonsmokers (p < 0.0001). The difference in the correlation for mFEV1/eFEV1 ratio between MZ and DZ twin pairs was 0.32 in nonsmokers and 0.19 in current smokers, suggesting a significant genetic influence on lung function that was modified in current smokers. Using structural equation modeling, the heritability estimate for mFEV1/eFEV1 ratio was found to be 66% (95% confidence interval [CI], 59 to 72%) in nonsmokers but significantly reduced to 32% (95% CI, 12 to 53%) in current smokers. However, there was no clear difference in the heritability of mFEV1/eFEV1 ratio between nonsmokers and ex-smokers.

Conclusion: Genes are the major influence on the variability of mFEV1/eFEV1 ratio in nonsmokers. However, this strong genetic influence is strongly modified by an interaction with cigarettes.

Key Words: FEV1 • genetics • measured to predicted FEV1 ratio • smoking • twins






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