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Lung function is an important predictor of morbidity and mortality, with accelerated lung function
decline reported to have immense consequences for the world’s healthcare systems. The lung function decline
across individual’s lifetime is a consequence of age-related changes in lung anatomical structure and combination
of various environmental factors; however, the exact molecular mechanisms contributing to this decline are not
fully understood. DNA methylation is an epigenetic modification that changes across individual’s lifetime, as well as
allows for interplay between environmental and genetic factors. DNA methylation plays a crucial role in regulation
of gene expression, with increasing evidence linking aberrant DNA methylation levels with a number of common
human diseases. In this study, we investigated possible associations between genome-wide DNA methylation levels
and lung function in 169 pairs of middle-aged monozygotic twins (86 male pairs: mean age (min-max) = 66 years
(57–79); 83 female pairs: mean age (min-max) = 66 years (56–78)). The twins were collected from the Danish Twin
Registry and were examined at baseline (1998–1999) and follow-up (2008–2011) visits. Using the twin design, we
correlated intra-pair differences in cross-sectional and longitudinal lung function with intra-pair blood DNA
methylation differences at follow-up by linear regression analyses adjusted for sex, age, BMI, smoking, and blood
cell composition measured for each individual with the use of flow cytometry.