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First published online on November 7, 2007
Chest, doi:10.1378/chest.07-1438
A more recent version of this article appeared on December 1, 2007
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The Interaction of Genes and Smoking on Forced Expiratory Volume: A Classic Twin Study

Guangju Zhai, PhD1; Ana M Valdes, PhD1; Lynn Cherkas, PhD1; Gail Clement, RGN1; David Strachan, MD2 and Tim D Spector, MD1

1Twin Research & Genetic Epidemiology Unit, King's College London School of Medicine, UK 2Division of Community Health Sciences, St George's, University of London, UK

guangju.zhai{at}kcl.ac.uk

Abstract

BackgroundGenetic influences on lung function measured by the forced expiratory volume in one second (FEV1) have been reported from twin and family studies. The aim of this study was to estimate heritability of the ratio of measured (mFEV1) to expected (eFEV1) FEV1 in a Caucasian population and to examine the interaction between genetic factors and smoking on this ratio.

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

ResultsA total of 475 MZ and 1054 DZ twin pairs with a mean age of 47 (range 18 - 84) participated. The ratio of mFEV1 to eFEV1 was 0.057 lower in smokers than non-smokers (p<0.0001). The difference in the correlation for the mFEV1 to eFEV1 ratio between MZ and DZ twin pairs was 0.32 in non-smokers and 0.19 in current smokers, suggesting a significant genetic influence on lung function that was modified in current smokers. Using structural equation modelling, the heritability estimate for the mFEV1 to eFEV1 ratio was found to be 66% (95% CI 59 - 72%) in non-smokers but significantly reduced to 32% (95% CI 12 - 53%) in current smokers. However, there was no clear difference in the heritability of the mFEV1 to eFEV1 ratio between non-smokers and ex-smokers.

ConclusionGenes are the major influence on the variability of the ratio of mFEV1 to eFEV1 in non-smokers. However, this strong genetic influence is strongly modified by an interaction with cigarettes.

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






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