Genetic and environmental influence on lung function impairment in Swedish twins

Abstract

BackgroundThe understanding of the influence of smoking and sex on lung function and symptoms is important for understanding diseases such as COPD. The influence of both genes and environment on lung function, smoking behaviour and the presence of respiratory symptoms has previously been demonstrated for each of these separately. Hence, smoking can influence lung function by co-varying not only as an environmental factor, but also by shared genetic pathways. Therefore, the objective was to evaluate heritability for different aspects of lung function, and to investigate how the estimates are affected by adjustments for smoking and respiratory symptoms.MethodsThe current study is based on a selected sample of adult twins from the Swedish Twin Registry. Pairs were selected based on background data on smoking and respiratory symptoms collected by telephone interview. Lung function was measured as FEV1, VC and DLco. Pack years were quantified, and quantitative genetic analysis was performed on lung function data adjusting stepwise for sex, pack years and respiratory symptoms.ResultsFully adjusted heritability for VC was 59% and did not differ by sex, with smoking and symptoms explaining only a small part of the total variance. Heritabilities for FEV1 and DLco were sex specific. Fully adjusted estimates were10 and 15% in men and 46% and 39% in women, respectively. Adjustment for smoking and respiratory symptoms altered the estimates differently in men and women. For FEV1 and DLco, the variance explained by smoking and symptoms was larger in men. Further, smoking and symptoms explained genetic variance in women, but was primarily associated with shared environmental effects in men.ConclusionDifferences between men and women were found in how smoking and symptoms influence the variation in lung function. Pulmonary gas transfer variation related to the menstrual cycle has been shown before, and the findings regarding DLco in the present study indicates gender specific environmental susceptibility not shown before. As a consequence the results suggest that patients with lung diseases such as COPD could benefit from interventions that are sex specific.

Genetic Influences on Pulmonary Function: A Large Sample Twin Study

“…This sample size is hardly sufficient for the modern variance component models we have applied. Results from a relatively small-sized twin study tried to address the question of sex differences in heritability of FEV 1 and FVC by using variance components analysis and found sex differences in the genetic contribution to FEV 1 with heritability being nonsignificant for males [22]. That study, however, consisted of only 176 complete twin pairs compared to the more than 1,500 complete pairs in our study, and the selection criteria of that study were based on the presence of respiratory symptoms [22] which differed from our study.…”

Total desmosines in plasma and urine correlate with lung function

“…These twins were invited to participate in more indepth measures of lung function. The selection of subjects was initially conducted for a heritability study, as described previously, in a manner such that disease-concordant and -discordant twins were prioritised over symptom-free twin pairs [15]. The selection was also based on feasibility aspects, such as geography, budget and personnel.…”

Heritability of Lung Function: A Twin Study Among Never-Smoking Elderly Women

“…Genetics affects both smoking and body composition (Ordonana et al, 2007;Vink et al, 2005), and together with age, they comprise the main factors modifying lung function heritability (Amara et al, 2001;Hallberg et al, 2010;Wilk et al, 2000). Previous studies on lung function heritability are cross-sectional and include smokers and non-smokers.…”

“…estimated multivariate-adjusted heritabilities are 40%-65% for FEV1, 40%-55% for FVC, and 45% for FEV1/FVC ratio (Hallberg et al, 2010;McClearn et al, 1994;Palmer et al, 2001;Wilk et al, 2000). Genome-wide association (GWA) studies have identified multiple single-nucleotide polymorphisms (SNPs) associated with lung function (Hancock et al, 2010;Repapi et al, 2010).…”