Study Population
The TCHS was a population-based prospective study that comprised two cohorts of children recruited from 14 communities across Taiwan. Cohort 1 was initiated in 2007 and cohort 2 in 2010; children were aged between 9 and 12 years old at the time of enrollment; and were followed until they turned 18 years old. Data collection includes parent- and children-filled questionnaires on atopy diseases, adiposity measures, pulmonary function tests, airway inflammation measures, physical fitness assessment, pubertal development record, and oral mucosa samples for DNA extraction. The cross-sectional analysis, involved 3233 children in cohort 1 and 2732 children in cohort 2, with complete data on adiposity, asthma outcomes, mediators at the age of 12 years, and genotype data. Detailed study design and recruitment strategy have been published15 and described on the online supplementary file. Informed consent was obtained from all participating parents and children. This study was approved by the ethics committee of institute and was conducted according to the Declaration of Helsinki.
After identification of the critical mediators, we further used the annual follow-up data which assessed the mediators from age 10 to age 12 in TCHS to approve the temporal mediating causality. The analyses herein involved data beginning from 2010 Survey which contained adiposity measurement, asthma outcome, puberty stage assessment, physical fitness measurement, and pulmonary function tests. Detailed study design were described in the online supplementary material.