Copy number variants differ in frequency across genetic ancestry groups

Copy number variants (CNVs), which are duplicated or deleted genomic segments larger than 1000 base pairs1, have been implicated in a variety of neuropsychiatric and cognitive phenotypes2-4. In the first large-scale of examination of genome-wide CNV frequencies across ancestry groups, we found that deleterious CNVs are less prevalent in non-European ancestry groups than they are in European ancestry groups of both the UK Biobank (UKBB) and a US replication cohort (SPARK). We also identified specific recurrent CNVs that consistently differ in frequency across ancestry groups in both the UKBB and SPARK. These ancestry-related differences in CNV prevalence present in both an unselected community population and a family cohort enriched with individuals diagnosed with autism spectrum disorder (ASD) strongly suggest that genetic ancestry should be considered when probing associations between CNVs and health outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by National Institute of Mental Health (NIMH) grant number U01-MH119690. ### 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: We obtained de-identified data from the UK Biobank under application number 40980. The UK Biobank has ethical approval from the North West Multi-centre Research Ethics Committee as a Research Tissue Bank approval. All recruiting sites for SPARK delegated institutional oversight of the study to Western Institutional Review, a central institutional review board, which gave ethical approval under protocol #20151664. The Institutional Review Board of Boston Children's Hospital gave ethical approval for this work using only publicly available, de-identified data from the UK Biobank and SPARK. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript.