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Irritability is frequently observed in childhood neurodevelopmental conditions, yet its aetiology is largely unknown. Genetic variation may play a role, but there is a sparsity of studies investigating the presentation of irritability in young people with ND-CNVs. This study aimed to investigate whether there is a difference in irritability in young people with rare ND-CNVs compared to those without ND-CNVs, and to what extent irritability is associated with psychiatric diagnoses and cognitive ability (IQ). Irritability and broader psychopathology were assessed in 485 young people with ND-CNVs and 164 sibling controls, using the child and adolescent psychiatric assessment. Autism was assessed using the social communication questionnaire, and intelligence quotient (IQ) by the Wechsler abbreviated scale of intelligence. Fifty four percent of young people with ND-CNVs met the threshold for irritability; significantly more than controls (OR\u2009=\u20093.77, CI\u2009=\u20093.07\u20137.90,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20095.31\u2009\u00d7\u200910\n                    <jats:sup>\u221211<\/jats:sup>\n                    ). When controlling for the presence of other psychiatric comorbidities, ND-CNV status was still associated with irritability. There was no evidence for a relationship between irritability and IQ. Irritability is an important aspect of the clinical picture in young people with ND-CNVs. This work shows that genetic variation is associated with irritability in young people with ND-CNVs, independent of psychiatric comorbidities or IQ impairment. Clinicians should be aware of this increased risk to inform management and interventions.\n                  <\/jats:p>","DOI":"10.1038\/s41398-024-02975-z","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T09:04:46Z","timestamp":1718701486000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Irritability in young people with copy number variants associated with neurodevelopmental disorders (ND-CNVs)"],"prefix":"10.1038","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3433-4784","authenticated-orcid":false,"given":"Jessica H.","family":"Hall","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2590-2874","authenticated-orcid":false,"given":"Samuel J. R. 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Cognit Behav Ther. 2023;16:e3.","journal-title":"Cognit Behav Ther"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02975-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02975-z","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02975-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T09:05:13Z","timestamp":1718701513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02975-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,18]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2975"],"URL":"https:\/\/doi.org\/10.1038\/s41398-024-02975-z","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.05.23299440","asserted-by":"object"}]},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,18]]},"assertion":[{"value":"24 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 June 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki declaration of 1975, as revised in 2008. Written consent was given by the primary caregiver and consent or assent by the young people as applicable. All procedures involving human subjects\/patients were approved by the appropriate university and NHS ethics and research and development committees; the NHS London Queen Square Research Ethics Committee (14\/LO\/1069) and the South East Wales Research Ethics Committee (09\/WSE04\/22).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"JHH, SJRAC, JW, PH and JH declaration of interest: none. DS reports a grant from Sarepta Therapeutics outside the scope of this work. MJO reports grants from Akrivia Health and Takeda Pharmaceuticals outside the scope of the present work. MBMvdB reports a grant from Takeda Pharmaceuticals outside the scope of the present work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"259"}}