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

Patricia Kipkemoi; Heesu Ally Kim; Bjorn Christ; Emily O'Heir; Jake Allen; Christina Austin-Tse; Samantha Baxter; Harrison Brand; Sam Bryant; Nick Buser; Victoria de Menil; Emma Eastman; Serini Murugasen; Alice Galvin; Martha Kombe; Alfred Ngombo; Beatrice Mkubwa; Paul Mwangi; Collins Kipkoech; Alysia Lovgren; Daniel G MacArthur; Brigitte Melly; Katini Mwangasha; Alicia Martin; Lethukuthula L Nkambule; Alba Sanchis-Juan; Moriel Singer-Berk; Michael E Talkowski; Grace VanNoy; Celia van der Merwe; NeuroDev Project; Charles Newton; Anne O'Donnell-Luria; Amina Abubakar; Kirsten A Donald; Elise B Robinson

doi:10.1016/j.neuron.2023.06.010

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

Neuron. 2023 Sep 20;111(18):2800-2810.e5. doi: 10.1016/j.neuron.2023.06.010. Epub 2023 Jul 17.

Authors

Patricia Kipkemoi¹, Heesu Ally Kim², Bjorn Christ³, Emily O'Heir², Jake Allen², Christina Austin-Tse⁴, Samantha Baxter², Harrison Brand⁵, Sam Bryant², Nick Buser², Victoria de Menil⁶, Emma Eastman³, Serini Murugasen³, Alice Galvin², Martha Kombe⁷, Alfred Ngombo⁷, Beatrice Mkubwa⁷, Paul Mwangi⁷, Collins Kipkoech⁷, Alysia Lovgren², Daniel G MacArthur², Brigitte Melly³, Katini Mwangasha⁷, Alicia Martin⁸, Lethukuthula L Nkambule⁸, Alba Sanchis-Juan⁵, Moriel Singer-Berk², Michael E Talkowski⁵, Grace VanNoy², Celia van der Merwe²; NeuroDev Project; Charles Newton⁹, Anne O'Donnell-Luria¹⁰, Amina Abubakar¹¹, Kirsten A Donald¹², Elise B Robinson¹³

Affiliations

¹ Neuroscience Unit, KEMRI-Wellcome Trust, Center for Geographic Medicine Research Coast, Kilifi, Kenya; Complex Trait Genetics Department, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
² The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
³ Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, 4th Floor ICH Building, Rondebosch, South Africa.
⁴ The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
⁵ The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA.
⁶ The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁷ Neuroscience Unit, KEMRI-Wellcome Trust, Center for Geographic Medicine Research Coast, Kilifi, Kenya.
⁸ Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
⁹ Neuroscience Unit, KEMRI-Wellcome Trust, Center for Geographic Medicine Research Coast, Kilifi, Kenya; Department of Psychiatry, University of Oxford, London, UK; Institute of Human Development, Aga Khan University, Nairobi, Kenya.
¹⁰ The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Division of Genetics and Genomics, Boston Children's Hospital, Boston, MA, USA.
¹¹ Neuroscience Unit, KEMRI-Wellcome Trust, Center for Geographic Medicine Research Coast, Kilifi, Kenya; Department of Psychiatry, University of Oxford, London, UK; Institute of Human Development, Aga Khan University, Nairobi, Kenya. Electronic address: amina.abubakar@aku.edu.
¹² Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital and University of Cape Town, 4th Floor ICH Building, Rondebosch, South Africa; Neuroscience Institute, University of Cape Town, Groote Schuur Hospital, Observatory, Cape Town, South Africa. Electronic address: kirsty.donald@uct.ac.za.
¹³ The Broad Institute of MIT and Harvard, Cambridge, MA, USA; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: erob@broadinstitute.org.

PMID: 37463579
DOI: 10.1016/j.neuron.2023.06.010

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.

Keywords: Kenya; South Africa; autism; de novo variants; developmental disorders; diverse populations; exome sequencing; genetics; intellectual disability; phenotypes.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autistic Disorder* / genetics
Child
Developmental Disabilities / genetics
Exome
Humans
Intellectual Disability* / genetics
Neurodevelopmental Disorders* / genetics
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding