Gene copy number variation in pediatric mental illness in a general population

We assessed the relationship of gene copy number variation (CNV) in mental health/neurodevelopmental traits and diagnoses, physical health, and cognitive biomarkers in a community sample of 7,100 unrelated European, and East Asian children and youth (Spit for Science). Diagnoses of mental health disorders were found in 17.5% of participants and 27.6% scored in the highest 10% on either or both ADHD and OCD trait measures. Clinically relevant CNVs were present in 3.9% of participants and were associated with elevated scores on a continuous measure of ADHD ( p =5.0×10−3), on a cognitive biomarker of mental health (response inhibition ( p =1.0×10−2)), and on prevalence of mental disorders ( p =1.9×10−6, odds ratio: 3.09). With a rise of mental illness, our data establishes a baseline for delineating genetic contributors in paediatric-onset conditions. One Sentence Summary Copy number variation predicts neurodevelopmental and mental health phenotypes in the general population. ### Competing Interest Statement RJS consults for Highland Therapeutics and Purdue Pharma. SWS is on the Scientific Advisory Committees of Population Bio, and serves as an Academic Consultant for the King Abdulaziz University. These relationships did not influence data interpretation or presentation during this study. The other authors declare no conflict of interest. ### Funding Statement This study was funded by operating grants from the Canadian Institutes of Health Research award to PDA (MOP106573) and RJS (MOP93696). It was also supported by grants from Genome Canada, Canada Foundation for Innovation, Government of Ontario, Canadian Institutes of Health Research, The Hospital for Sick Children Foundation and the University of Toronto McLaughlin Centre. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. RJS holds the Toronto Dominion Bank Financial Group Chair in Child and Adolescent Psychiatry. PDA holds the Alberta Innovates Health Solutions (AIHS) Translational Health Chair in Child and Youth Mental Health at the University of Calgary. SWS holds the Northbridge Chair in Paediatric Research, The Hospital for Sick Children and the University of Toronto. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Research Ethics Board of The Hospital for Sick Children gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The relevant genotype data and CNVs are being prepared for submission to the European Genome-Phenome Archive and the dbVar Database, respectively.