Phenotype and genetic analysis of data collected within the first year of NeuroDev

Summary Genetic association studies have made significant contributions to our understanding of the aetiology of neurodevelopmental disorders (NDDs). However, the vast majority of these studies have focused on populations of European ancestry, and few include individuals from the African continent. The NeuroDev project aims to address this diversity gap through detailed phenotypic and genetic characterization of children with NDDs from Kenya and South Africa. Here we present results from NeuroDev’s first year of data collection, including phenotype data from 206 cases and clinical genetic analysis of 99 parent-child trios. The majority of the cases met criteria for global developmental delay/intellectual disability (GDD/ID, 80.3%). Approximately half of the children with GDD/ID also met criteria for autism, and 14.6% met criteria for autism alone. Analysis of exome sequencing data identified a pathogenic or likely pathogenic variant in 13 (17%) of the 75 cases from South Africa and 9 (38%) of the 24 cases from Kenya, as well as 7 total cases with suspicious variants of uncertain significance (VUS) in emerging disease genes that were matched through the MatchMaker Exchange. Data from the trio pilot cases has already been made publicly available, and the NeuroDev project will continue to develop resources for the global genetics community. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement NeuroDev is supported by the Stanley Center for Psychiatric Research at the Broad Institute, a grant from SFARI (704413, E.B.R), and by the National Institute of Mental Health of the National Institutes of Health under Award Number U01MH119689. Research reported in this publication was also supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number R01HD102975. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Sequencing was provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. ### 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: Ethical approval was sought in the site institutional review boards as well as at the Harvard T.H Chan School of Public Health. In Kilifi, Kenya, approval was granted by the Scientific Ethics and Review Unit (KEMRI/SERU/CGMR-C/104/3629) and Health Research Ethics Committee (HREC REF:810/2016) in Cape Town, South Africa. 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 trio data presented here can be accessed through National Human Genome Research Institute (NHGRI) Analysis Visualization and Informatics Lab-space (ANVIL) controlled access data repository.