Peer-reviewed article
Early-life internalizing behavioral trajectories and childhood-onset asthma: An epigenetic link.
Yoon J, Lee SH, Kim J, Hong K, Lee SY et al. ·
Summary
Written by AI, not yet AICS's view ·Key points
Limitations
Abstract
Background Behavioral problems and asthma in childhood are considered related despite the debatable causal relationship and unknown mechanisms. We investigated whether early-life behavioral problem trajectories affect the risk of childhood asthma and ascertained potential DNA-methylation mechanisms. Methods Based on two independent birth cohorts, this study included 1041 and 1647 children aged 6-10 and 6-7 years in the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) study and Panel Study on Korean Children (PSKC), wherein asthma was defined by a physician's diagnosis and parental questionnaire, respectively. The Korean version of the Child Behavior Checklist (CBCL) was administered at ages 2-6 years. The CBCL trajectories were identified using a latent generalized mixture model. Blood samples from 7-year-old participants were used for DNA-methylation profiling and quantifying metabolites and proteins. Results Trajectories with high internalizing behavioral problem scores in preschool age were significantly associated with childhood-onset asthma. Increased CBCL anxiety/depression scores at age 2 (COCOA) and somatization scores at ages 4 and 6 (COCOA and PSKC) significantly increased the risk of asthma symptoms and current asthma. In an exploratory sub-study, DNA-methylation analysis suggested hypomethylation of HAL and MAD1L1 in children with co-occurring asthma and behavioral problems, accompanied by higher HAL protein and lower circulating histidine. Conclusion Early-life internalizing behavioral problem trajectories precede childhood asthma, which may be mediated by methylation, especially of HAL and MAD1L1.