# Genetic Architecture of Early-Onset Psychosis in Mexicans (EPIMex)

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $2,351,491

## Abstract

PROJECT SUMMARY/ABSTRACT
Despite recent progress, clinical heterogeneity has likely hindered efforts to clearly delineate the genetic
architecture of psychotic disorders like schizophrenia and bipolar disorder. However, this heterogeneity also
presents an opportunity for studying individuals with extreme phenotypes, virulent forms of the illness with
putatively more homogeneous etiologies. Early onset psychosis (EOP, onset prior to 18 years) represents such
an extreme phenotype, with dramatically higher rates of rare deleterious mutations in EOP than adult-onset
psychosis. Consequently, studying EOP cohorts provides a unique opportunity to discover rare genetic loci
influencing illness risk. We will deep phenotype and sequence 1900 EOP probands and 1900 non-psychotic,
demographically matched youth. For 400 probands, both parents and a non-psychotic sibling will be recruited
to facilitate the search for inherited and de novo mutations associated with EOP (n=1200 family members).
Children and adolescents and their families will be recruited from a single, large public pediatric psychiatric
hospital in Mexico City. To date, most psychiatric genetic studies focus on European-ancestry (EA) cohorts,
while excluding of other ancestry groups. Yet, no single population is sufficient to fully illuminate the genetic
architecture of complex traits like psychosis, and the EA focus could exacerbate health care disparities. Latinos
make up ~8% of the world population (~18% of the US population) but appear in less than 1% of published
genome-wide studies. Complicating matters, Latinos are genetically heterogeneous, with substantial
differences between Central and South American and Caribbean populations, reflecting continental-level
ancestral group admixture and the substructure of local Indigenous American populations. As 62% of the
Latinos in the US are of Mexican origin findings from the Mexican population are directly relevant for most
individuals in the nation’s largest racial/ethnic minority. During our initial 1-year project, we recruited 1000
participants from the same psychiatric hospital and using identical procedures, thus demonstrating the
feasibility of the current study. Combining these 1000 individuals with the additional 5000 participants we now
propose to acquire, we aim to: 1) characterize EOP probands and siblings in terms of cognitive and
psychosocial functioning, frequency of adverse life events, social determinants, and cannabis use; 2)
document the prevalence of rare loss of function mutations and CNVs previously associated with
schizophrenia or autism spectrum disorder in EOP participants relative to their unaffected family members and
demographic and population controls; and 3) utilize ancestry analysis to identify chromosomal regions and
runs of homozygosity shared in common by multiple unrelated EOP cases but not by unaffected individuals.
David Glahn (BCH), Laura Almasy (CHOP), Humberto Nicolini (Instituto Nacional de Medicina Genómic...

## Key facts

- **NIH application ID:** 10886810
- **Project number:** 5R01MH133621-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Laura A. Almasy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,351,491
- **Award type:** 5
- **Project period:** 2023-07-14 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10886810

## Citation

> US National Institutes of Health, RePORTER application 10886810, Genetic Architecture of Early-Onset Psychosis in Mexicans (EPIMex) (5R01MH133621-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10886810. Licensed CC0.

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