Doctor of Philosophy
Syed Hasan Arshad
The period from pre-adolescence to post-adolescence of life is significant for lung function development when it reaches its maximal level. Reduced lung function development in early life predisposes to respiratory and other chronic diseases later in life and is associated with early mortality. DNA methylation (DNA-M) is a potential epigenetic mechanism through which environmental exposures can exert their eects on gene expression and disease risk. It acts as an epigenetic memory of past exposure such as pubertal onset. DNA-M changes over time in response to biological aging, sex, and environmental factors, and such changes also occur in the adolescence period. Given that lung function is associated with DNA-M, it is crucial to understand that the role of epigenetics on lung function development, changes, and patterns during pre- and post-adolescence, which is a critically important period of life. This dissertation is composed of three aims that correspond to three major hypotheses. In aim 1, the association of changes in DNA-M with changes of lung function during adolescence was examined. In aim 2, the association of DNA-M at an earlier age with lung function at a later age was assessed, and further whether such association is differed by sex was examined. In aim 3, the associations of pre-adolescence DNA-M with lung function trajectory from childhood to adulthood was assessed in males and females, separately. All the aims were examined in a genome-wide approach in the Isle of Wight birth cohort study (IOWBC) as a discovery cohort and then the findings were further examined in an independent cohort, Avon Longitudinal Study of Parents and Children (ALSPAC). The findings of aim 1 were examined in another independent cohort, Children, Allergy, Milieu, Stockholm, Epidemiology (BAMSE), in addition to ALSPAC. In aim 1, DNA-M changes in 11 CpGs were found to be associated with changes in FEV1/FVC in females in adolescence, such findings were not found in males. In aim 2, 8 and 13 CpGs were longitudinally associated with lung function for main and sex-specific effects, respectively and in aim 3, pre-adolescence DNA-M at 44 CpGs was associated with the trajectories from pre-adolescence to post-adolescence.
Dissertation or thesis originally submitted to ProQuest
Sunny, Shadia Khan, "Epigenetics and lung function during pre- and post-adolescence, genome-scale studies" (2021). Electronic Theses and Dissertations. 2967.