Genetic Influences on Pulmonary Function: A Large Sample Twin Study

Abstract

Heritability of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) has not been previously addressed in large twin studies. We evaluated the genetic contribution to individual differences observed in FEV1FVC, and PEF using data from the largest population-based twin study on spirometry. Specially trained lay interviewers with previous experience in spirometric measurements tested 4,314 Danish twins (individuals), 46–68 years of age, in their homes using a hand-held spirometer, and their flow-volume curves were evaluated. Modern variance component sex-limitation models were applied to evaluate possible genetic differences between the sexes for FEV1FVC, and PEF. Estimates were adjusted for age, height, and smoking. For FEV1additive genetic effects of 61% (95% CI 56–65) were observed. For FVC, the additive genetic contribution was 26% (3–49%) and the dominant genetic contribution was 29% (4–54%). For PEF, our models showed an additive genetic contribution of 43% (31–52%) for men, but genetic influences were not significant in women. We found no significant differences between dizygotic same-sex twins and dizygotic opposite-sex twins for FEV1FVC, and PEF, suggesting absence of qualitative genetic differences between the sexes. Sex-difference heritability for PEF suggested possible quantitative genetic differences between the sexes for this index. Genetic effects contributed significantly to individual differences observed in FEV1FVC, and PEF. Qualitative sex differences were absent for all spirometric measures, while quantitative sex differences were observed only for PEF, with heritability being substantial in men but negligible in women.

Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study

“…Our findings on the heritability of lung function are also in line with those previously reported (12,32,33). In the current sample, additive genetic factors accounted for 65% of the variability in FEV 1 and 67% of FVC.…”

“…In the current sample, additive genetic factors accounted for 65% of the variability in FEV 1 and 67% of FVC. Very similar heritability estimates of 61% and 67% for FEV 1 in older twins have been reported earlier (12,34). In addition, our estimate of the genetic contribution to FVC is comparable with the estimate (68%) reported by Tarnoki et al (32) and slightly higher than that (55%) reported by Ingebrigtsen and co-workers (12).…”

“…Very similar heritability estimates of 61% and 67% for FEV 1 in older twins have been reported earlier (12,34). In addition, our estimate of the genetic contribution to FVC is comparable with the estimate (68%) reported by Tarnoki et al (32) and slightly higher than that (55%) reported by Ingebrigtsen and co-workers (12). Although, the interaction of genes and smoking may influence lung function (35), our data showed that current or former smoking had minor effects on the heritability estimates of lung function.…”

“…Of the potential unique environmental factors, tobacco smoke is known to promote aging processes and cellular senescence (38) and telomere shortening (8) in addition to its known damaging effects on lung function (39). We found that current smoking, but not previous smoking was significantly associated with lung function variables FEV 1 , PEF and the FEV 1 /FVC ratio, but not FVC or LTL, and that smoking had a minor influence on the genetic and environmental components of the lung function variables, as observed previously (12). Our data included only a few smokers and there was a large heterogeneity in smoking exposure and its amount and duration.…”

“…Both LTL (11) and lung function (12,13) are known to be genetically regulated, and specific genes have been identified through genome-wide associations studies (14), but the known genes account for only a fraction of the heritable component estimated from family and twin data. Inter-individual variation in the amount and rate of decline with age both in lung function and in LTL has been less studied, although it is known to be affected by both genetic and environmental factors.…”