{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T14:03:58Z","timestamp":1776348238687,"version":"3.51.2"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DP1DA054373"],"award-info":[{"award-number":["DP1DA054373"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Externalizing behaviors in children, such as aggression, hyperactivity, and defiance, are influenced by complex interplays between genetic predispositions and environmental factors, particularly parental behaviors. Unraveling these intricate causal relationships can benefit from the use of robust data-driven methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>We developed \u201cHillclimb-Causal Inference,\u201d a causal discovery approach that integrates the Hill Climb Search algorithm with a customized Linear Gaussian Bayesian Information Criterion (BIC). This method was applied to data from the Adolescent Brain Cognitive Development (ABCD) Study, which included parental behavior assessments, children\u2019s genotypes, and externalizing behavior measures. We performed dimensionality reduction to address multicollinearity among parental behaviors and assessed children\u2019s genetic risk for externalizing disorders using polygenic risk scores (PRS), which were computed based on GWAS summary statistics from independent cohorts. Once the causal pathways were identified, we employed structural equation modeling (SEM) to quantify the relationships within the model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified prominent causal pathways linking parental behaviors to children\u2019s externalizing outcomes. Parental alcohol misuse and broader behavioral issues exhibited notably stronger direct effects (0.33 and 0.20, respectively) compared to children\u2019s PRS (0.07). Moreover, when considering both direct and indirect paths, parental substance misuse (alcohol, drugs, and tobacco) collectively resulted in a total effect exceeding 1.1 on externalizing behaviors. Bootstrap and sensitivity analyses further validated the robustness of these findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>Parental behaviors exert larger effects on children\u2019s externalizing outcomes than genetic risk, suggesting potential targets for prevention and intervention. The Hillclimb-Causal framework provides a general, data-driven way to map causal pathways in developmental psychiatry and related domains.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jamia\/ocaf153","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T11:26:37Z","timestamp":1756725997000},"page":"1936-1946","source":"Crossref","is-referenced-by-count":3,"title":["Hillclimb-Causal Inference: a data-driven approach to identify causal pathways among parental behaviors, genetic risk, and externalizing behaviors in children"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0458-7140","authenticated-orcid":false,"given":"Mengman","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Neuroscience, The Scripps Research Institute , San Diego, CA 92037,","place":["United 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