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We investigated whether early\u2010life behavioral problem trajectories affect the risk of childhood asthma and ascertained potential DNA\u2010methylation mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Based on two independent birth cohorts, this study included 1041 and 1647 children aged 6\u201310 and 6\u20137\u2009years 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\u20136\u2009years. The CBCL trajectories were identified using a latent generalized mixture model. Blood samples from 7\u2010year\u2010old participants were used for DNA\u2010methylation profiling and quantifying metabolites and proteins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Trajectories with high internalizing behavioral problem scores in preschool age were significantly associated with childhood\u2010onset 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\u2010study, DNA\u2010methylation analysis suggested hypomethylation of\n                      <jats:italic>HAL<\/jats:italic>\n                      and\n                      <jats:italic>MAD1L1<\/jats:italic>\n                      in children with co\u2010occurring asthma and behavioral problems, accompanied by higher HAL protein and lower circulating histidine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Early\u2010life internalizing behavioral problem trajectories precede childhood asthma, which may be mediated by methylation, especially of\n                      <jats:italic>HAL<\/jats:italic>\n                      and\n                      <jats:italic>MAD1L1<\/jats:italic>\n                      .\n                    <\/jats:p>\n                    <jats:p>\n                      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link"],"prefix":"10.1111","volume":"37","author":[{"given":"Jisun","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Pediatrics Asan Medical Center, University of Ulsan College of Medicine  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung\u2010Hwa","family":"Lee","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiseon","family":"Kim","sequence":"additional","affiliation":[{"name":"Asan Institute for Life Sciences Asan Medical Center  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungmo","family":"Hong","sequence":"additional","affiliation":[{"name":"Major in Psychotherapy, Graduate School of Health &amp; Welfare Baekseok University  Cheonan Republic of 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