Early-life internalizing behavioral trajectories and childhood-onset asthma: An epigenetic link.

Authors

Jisun Yoon, Seung-Hwa Lee, Jiseon Kim, Kyungmo Hong, So-Yeon Lee, Hea Young Oh, Sungsu Jung, Da Kyeong Lee, Eom Ji Choi, Ji Soo Park, Youn Ho Shin, Kyung Won Kim, Kangmo Ahn, Jihyun Kim, Yee-Jin Shin, Kyung-Sook Lee, Dong In Suh, Soo-Jong Hong, Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) and Panel Study on Korean Children (PSKC) Study Groups

Published in

Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. Volume 37. Issue 8. Pages e70436.

Abstract

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.
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.
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.
Early-life internalizing behavioral problem trajectories precede childhood asthma, which may be mediated by methylation, especially of HAL and MAD1L1.

PMID:
42605184
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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