{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:12:50Z","timestamp":1792102370259,"version":"4.4.0"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"Abstract<\/jats:title>\n \n Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGG\n overall<\/jats:sub>\n ) was 3.31% (SE\u2009=\u20090.0038). We found no genome-wide significant SNPs for AGG\n overall<\/jats:sub>\n . The gene-based analysis returned three significant genes:\n ST3GAL3<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20091.6E\u201306),\n PCDH7<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20092.0E\u201306), and\n IPO13<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20092.5E\u201306). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (\n r<\/jats:italic>\n \n g<\/jats:italic>\n <\/jats:sub>\n ) among rater-specific assessment of AGG ranged from\n r<\/jats:italic>\n \n g<\/jats:italic>\n <\/jats:sub>\n \u2009=\u20090.46 between self- and teacher-assessment to\n r<\/jats:italic>\n \n g<\/jats:italic>\n <\/jats:sub>\n \u2009=\u20090.81 between mother- and teacher-assessment. We obtained moderate-to-strong\n r<\/jats:italic>\n \n g<\/jats:italic>\n <\/jats:sub>\n s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range\n \n \n $$\\left| {r_g} \\right|$$<\/jats:tex-math>\n \n \n \n \n \n r<\/mml:mi>\n <\/mml:mrow>\n \n g<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:mfenced>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n : 0.19\u20131.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (\n r<\/jats:italic>\n \n g<\/jats:italic>\n <\/jats:sub>\n \u2009=\u2009~\u22120.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range\n \n \n $$\\left| {r_g} \\right|$$<\/jats:tex-math>\n \n \n \n \n \n r<\/mml:mi>\n <\/mml:mrow>\n \n g<\/mml:mi>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:mfenced>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n : 0.46\u20130.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.\n <\/jats:p>","DOI":"10.1038\/s41398-021-01480-x","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T02:03:46Z","timestamp":1627610626000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Genetic association study of childhood aggression across raters, instruments, and age"],"prefix":"10.1038","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-5019","authenticated-orcid":false,"given":"Hill F.","family":"Ip","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camiel M.","family":"van der Laan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva M. 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JARQ was on the speakers\u2019 bureau and\/or acted as consultant Eli Lilly, Janssen-Cilag, Novartis, Shire, Lundbeck, Almirall, Braingaze, Sincrolab, Medicine, Exeltis, and Rubi\u00f3 in the last 5 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubi\u00f3, Shire, Medice, and Eli-Lilly. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 5 years: Eli-Lilly, Lundbeck, Janssen-Cilag, Actelion, Shire, Ferrer, Oryzon, Roche, Psious, and Rubi\u00f3.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"413"}}