# Elucidating the Genetic Etiology of Intellectual Disability in African, Asian, and European Families

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $623,770

## Abstract

PROJECT SUMMARY/ABSTRACT
 Intellectual disability (ID) affects 1-3% of the world population. Six and a half million Americans have been
diagnosed with ID. Identification of genes and variants that cause ID in a variety of populations. i.e., African,
Asian, and European is highly beneficial for understanding brain mechanism and function, development of
treatment modalities, and diagnosis through genetic screening. Although >1000 genes have been identified
for ID, most genes remain to be uncovered.
 For this study we will ascertain 500 ID families from Finland, Hungary (Romani and Magyar), Mali, and
Pakistan. Families with ID due to a FMR1 repeat expansion (Fragile X syndrome) or environmental exposures
(trauma or infection) will be excluded. The studied will consist of trios (affected proband and parents), nuclear
and extended families including those with consanguinity. Next-generation sequencing will be performed on
DNA samples obtained from the proband and his/her parents for the trios and on average three affected
members for the nuclear/extended families. Analysis of the sequence data will be performed by implementing
tools developed in house that are incorporated in Jupyter Notebooks using information on variant frequency,
deleterious status, and conservation as well as database annotations on clinical etiology, animal models, and
brain expression. Candidate variants will be validated and for nuclear/extended families tested for segregation
with ID using DNA samples obtained from all available family members. Three-dimensional protein modeling
will be performed to investigate how identified variants affect protein function. Once a putatively causal ID
variant is identified, we will screen our collection of ID pedigrees and use GeneMatcher to find additional ID
families that segregate potentially pathogenic variants within the same gene. For newly identified ID genes,
spatiotemporal expression profiling will be performed in the developing and adult brain and nervous system
to provide additional evidence of the gene’s involvement in ID etiology and to better understand how disruption
of the gene can impact brain function.
 ID has been understudied in African populations. The study of West Africans (Mali) should bring about new
knowledge which can directly impact African Americans since their ancestors were brought to the Americas
from West Africa through the trans-Atlantic slave trade. Pakistani families due to their size and structure are
highly beneficial in identify ID genes. The Hungarian Romani and the Finnish both belong to founder
populations which can aid in variant identification. This unique resource of families from Africa, Asia, and
Europe will aid in better understanding of the genetic etiology of ID and the role genetic plays in brain function.
The new knowledge obtained from this study should be beneficial to the health of minority and non-minority
American populations.

## Key facts

- **NIH application ID:** 10906931
- **Project number:** 5R01HD109342-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SUZANNE M LEAL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $623,770
- **Award type:** 5
- **Project period:** 2023-08-14 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906931

## Citation

> US National Institutes of Health, RePORTER application 10906931, Elucidating the Genetic Etiology of Intellectual Disability in African, Asian, and European Families (5R01HD109342-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10906931. Licensed CC0.

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