# Somatic Mosaicism in Neuropsychiatric Disorders

> **NIH NIH F31** · HARVARD MEDICAL SCHOOL · 2022 · $33,576

## Abstract

Project Abstract
 In the United States, neuropsychiatric disorders are the leading cause of disability. These disorders can
have deep consequences on different dimensions of the individual such as social and emotional. The standard
of diagnosis is based on relatively subjective criteria that tends to dichotomize disease categories, even when
individuals have a spectrum of presentations. This discordance emphasizes the need to further understand the
underlying patient biology. In the proposed study, I will focus on Schizophrenia (SCZ), Bipolar disorder (BP),
and ADHD, because even though they have many clinical differences they contribute to a great proportion of
years lived with disability in the United states, with a combined 4.38%. In addition, SCZ is one of the top 10
global causes of disability. Even though the great health burden of these disorders is known, their biological
mechanism remains greatly unknown. Genetic studies have implicated a strong genetic component for these
disorders, including inherited variants, as well as rare de novo mutations. However, it has recently been
proposed that somatic mosaicism might contribute partly to the missing risk. Somatic mutations have shown to
play an important pathogenic role in several neurodevelopmental disorders such epileptic focal cortical
dysplasia, Sturge-Weber disorder. Our lab and others have implicated mosaic single nucleotide variants
(SNVs) as well as copy number variants (CNVs) to autism spectrum disorder (ASD). Strong overlap in the
genetic architecture of ASD in multiple neuropsychiatric disorders has been reported. This observation poses
the question of whether somatic mutations could contribute to the genetic architecture of SCZ and related
disorders.
 With this grant, I propose to systematically test and characterize the contribution of somatic
mutations to the genetic architecture of neuropsychiatric disorders such as SCZ, BP, and ADHD. Aim 1
proposes to test the hypothesis that mosaic copy number variants (CNVs) contribute to these disorders. This
will be accomplished by leveraging a recently developed method by our collaborator Prof. Po Ru Loh. I will
enhance the robustness of the algorithm to varying array platforms to exploit large case-control SNP array
databases. This method will allow for the systematic identification and burden quantification of mosaic CNVs
across large datasets of SCZ, BP, ADHD from the Psychiatric Genomic Consortium. Aim 2 proposes to test the
hypothesis that mosaic SNVs contribute to these disorders. This will be accomplished by developing
methodology to identify mosaic SNVs from brain derived RNA-seq data, since there have been growing brain
derived RNA-seq databases for neuropsychiatric disorders with enough coverage to identify somatic SNVs
compared to whole exome and whole genome sequencing efforts. With this novel method it will be possible to
systematically characterize mutational burden and patterns across SCZ and BP from readily available dat...

## Key facts

- **NIH application ID:** 10360480
- **Project number:** 5F31MH124292-02
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Eduardo Antonio Maury
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $33,576
- **Award type:** 5
- **Project period:** 2021-03-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360480

## Citation

> US National Institutes of Health, RePORTER application 10360480, Somatic Mosaicism in Neuropsychiatric Disorders (5F31MH124292-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360480. Licensed CC0.

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