# Rare genetic disorders in NeuroDev: Insight into the genetic and phenotypic heterogeneity of ID, ASD and ADHD in South African Populations

> **NIH NIH U01** · BROAD INSTITUTE, INC. · 2021 · $1,127,917

## Abstract

Project Summary
Rare genetic disorders (RGDs) have provided a significant window into the genetic architecture of cognitive
and behavioral variation. They have also posed questions about the relationship between idiopathic and
syndromic forms of cognitive and behavioral disorders, and the role of genetic background in RGD expression.
Further, most genetic studies to date have focused on populations of European ancestry, meaning little is
known about RGD expression and variability in other populations. To address these gaps, we will leverage the
ongoing NeuroDev South Africa collection to genetically and phenotypically characterize 1,000 children aged
2-17, ascertained for Autism Spectrum Disorders, Intellectual Disability/Global Developmental Delay, and
Attention Deficit Hyperactive Disorder in Cape Town. The collection also includes 1,000 case parents and
1,000 unrelated, ancestry-matched controls. We will genetically characterize all 3,000 NeuroDev participants in
order to identify and investigate an estimated 300 RGD cases in the NeuroDev sample. We propose to use
medical record data to further characterize all NeuroDev cases which, in conjunction with the detailed
phenotype data collected as part of the core collection activity, will create uncommon opportunities for the
phenotypic comparison of RGD-based and idiopathic neuropsychiatric disorders (e.g. dimensional cognitive
and behavioral data, brain imaging, audiology data). With the aggregated data, we will compare the phenotypic
features of RGD-based and idiopathic neuropsychiatric disorders and highlight points of divergence, which will
be useful for addressing heterogeneity in future research, as well as in eventual treatment trials. Lastly, we
consider the role of genetic background in the variable expressivity of neuropsychiatrically-involved RGDs, in
terms of both genome-wide genetic risk for behavioral disorders and ancestral variation. These analyses will
address several critical questions about the biology and presentation of RGDs, as well as their relationship to
cognitive and behavioral disorders. The wide sharing of these data will permit further investigation at the field-
wide level.

## Key facts

- **NIH application ID:** 10201430
- **Project number:** 5U01MH119689-03
- **Recipient organization:** BROAD INSTITUTE, INC.
- **Principal Investigator:** Kirsty Donald
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,127,917
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201430

## Citation

> US National Institutes of Health, RePORTER application 10201430, Rare genetic disorders in NeuroDev: Insight into the genetic and phenotypic heterogeneity of ID, ASD and ADHD in South African Populations (5U01MH119689-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10201430. Licensed CC0.

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