Abstract
Genetic association studies have made significant contributions to our understanding of the etiology of neurodevelopmental disorders (NDDs). However, these studies rarely focused on 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. We present results from NeuroDev's first year of data collection, including phenotype data from 206 cases and clinical genetic analyses of 99 parent-child trios. Most 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. 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. Data from the trio pilot are publicly available, and the NeuroDev Project will continue to develop resources for the global genetics community.
Original language | English |
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Pages (from-to) | 2800-2810.e1-e5 |
Number of pages | 17 |
Journal | Neuron |
Volume | 111 |
Issue number | 18 |
Early online date | 17 Jul 2023 |
DOIs | |
Publication status | Published - 20 Sept 2023 |
Bibliographical note
Funding Information:We are extremely grateful to the family members for participating in this research. We are grateful to the clinical laboratories and biobank teams at KEMRI-Wellcome Trust and the University of Cape Town, the community liaison group and neuro-epilepsy clinic at the KEMRI-Wellcome Trust, and developmental and allied clinics at Red Cross Memorial Hospital. We acknowledge James Swanson, Edith Nolan, William Pelham, and team for the use of the SNAP-IV; David Skuse, Richard Warrington, Will Mandy, and team for the use of the 3Di and SCDC; the ASEBA team for the use of the CBCL; Christopher Molteno and team for the use of the Molteno Adapted Scales; and the John C. Raven, John H. Court, and team for the use of the Raven's Progressive Matrices. 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; the National Heart, Lung, and Blood Institute grant UM1HG008900; and in part by National Human Genome Research Institute grant R01HG009141. E.B.R. K.A.D. A.A. and C.N. designed the study. The NeuroDev Project members, including P.K. B.C. E.E. M.K. A.N. B.M. S.M. and K.M. were involved in data collection. H.A.K. E.O. J.A. S. Bryant, N.B. C.K. P.M. and B.M. were involved in the curation and analysis of the data. P.K. H.A.K. B.C. E.O. and E.B.R. wrote the manuscript with input from all authors. P.K. B.C. E.E. A.G. and K.M. were involved in project administration, and C.A.-T. S. Baxter, H.B. A.L. D.G.M. A.S.-J. M.S.-B. M.E.T. V.d.M. A.M. L.L.N. C.v.d.M. C.N. A.D.-L. A.A. K.A.D. and E.B.R. supervised various aspects of the project and the core project teams. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research.
Funding Information:
We are extremely grateful to the family members for participating in this research. We are grateful to the clinical laboratories and biobank teams at KEMRI-Wellcome Trust and the University of Cape Town, the community liaison group and neuro-epilepsy clinic at the KEMRI-Wellcome Trust, and developmental and allied clinics at Red Cross Memorial Hospital. We acknowledge James Swanson, Edith Nolan, William Pelham, and team for the use of the SNAP-IV; David Skuse, Richard Warrington, Will Mandy, and team for the use of the 3Di and SCDC; the ASEBA team for the use of the CBCL; Christopher Molteno and team for the use of the Molteno Adapted Scales; and the John C. Raven, John H. Court, and team for the use of the Raven’s Progressive Matrices. 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 ; the National Heart, Lung, and Blood Institute grant UM1HG008900 ; and in part by National Human Genome Research Institute grant R01HG009141 .
Publisher Copyright:
© 2023 The Authors
Funding
We are extremely grateful to the family members for participating in this research. We are grateful to the clinical laboratories and biobank teams at KEMRI-Wellcome Trust and the University of Cape Town, the community liaison group and neuro-epilepsy clinic at the KEMRI-Wellcome Trust, and developmental and allied clinics at Red Cross Memorial Hospital. We acknowledge James Swanson, Edith Nolan, William Pelham, and team for the use of the SNAP-IV; David Skuse, Richard Warrington, Will Mandy, and team for the use of the 3Di and SCDC; the ASEBA team for the use of the CBCL; Christopher Molteno and team for the use of the Molteno Adapted Scales; and the John C. Raven, John H. Court, and team for the use of the Raven's Progressive Matrices. 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; the National Heart, Lung, and Blood Institute grant UM1HG008900; and in part by National Human Genome Research Institute grant R01HG009141. E.B.R. K.A.D. A.A. and C.N. designed the study. The NeuroDev Project members, including P.K. B.C. E.E. M.K. A.N. B.M. S.M. and K.M. were involved in data collection. H.A.K. E.O. J.A. S. Bryant, N.B. C.K. P.M. and B.M. were involved in the curation and analysis of the data. P.K. H.A.K. B.C. E.O. and E.B.R. wrote the manuscript with input from all authors. P.K. B.C. E.E. A.G. and K.M. were involved in project administration, and C.A.-T. S. Baxter, H.B. A.L. D.G.M. A.S.-J. M.S.-B. M.E.T. V.d.M. A.M. L.L.N. C.v.d.M. C.N. A.D.-L. A.A. K.A.D. and E.B.R. supervised various aspects of the project and the core project teams. The authors declare no competing interests. We support inclusive, diverse, and equitable conduct of research. We are extremely grateful to the family members for participating in this research. We are grateful to the clinical laboratories and biobank teams at KEMRI-Wellcome Trust and the University of Cape Town, the community liaison group and neuro-epilepsy clinic at the KEMRI-Wellcome Trust, and developmental and allied clinics at Red Cross Memorial Hospital. We acknowledge James Swanson, Edith Nolan, William Pelham, and team for the use of the SNAP-IV; David Skuse, Richard Warrington, Will Mandy, and team for the use of the 3Di and SCDC; the ASEBA team for the use of the CBCL; Christopher Molteno and team for the use of the Molteno Adapted Scales; and the John C. Raven, John H. Court, and team for the use of the Raven’s Progressive Matrices. 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 ; the National Heart, Lung, and Blood Institute grant UM1HG008900 ; and in part by National Human Genome Research Institute grant R01HG009141 .
Funders | Funder number |
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Harvard Center for Mendelian Genomics | |
James Swanson, Edith Nolan | |
KEMRI-Wellcome Trust | |
SCDC | |
William Pelham | |
National Institutes of Health | U01MH119689 |
National Institutes of Health | |
National Institute of Mental Health | |
National Heart, Lung, and Blood Institute | R01HG009141, UM1HG008900 |
National Heart, Lung, and Blood Institute | |
National Human Genome Research Institute | |
National Eye Institute | |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | R01HD102975 |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | |
Broad Institute | |
Simons Foundation Autism Research Initiative | |
University of Cape Town |
Keywords
- autism
- de novo variants
- developmental disorders
- diverse populations
- exome sequencing
- genetics
- intellectual disability
- Kenya
- phenotypes
- South Africa