# 3/9 Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $188,643

## Abstract

PROJECT SUMMARY
 The International Consortium on Brain and Behavior Copy Number Variants (IBBC-CNVs) is a collaborative
effort of 9 institutions with complementary experience and expertise in phenomics and genomics. The 22q11.2
and 16p11.2 loci are associated with significant risk for neuropsychiatric disorders across the lifespan. The
clinical presentations are heterogeneous, manifesting in a range of developmental neuropsychiatric disorders,
including Attention Deficit Hyperactivity, Anxiety, Autism Spectrum, and Psychosis Spectrum Disorders. Taking
a `genetics first' approach of ascertaining patients based on known, homogeneous genetic etiologies will allow
us to overcome barriers posed by the genetic and phenotypic complexity of idiopathic developmental
neuropsychiatric disorders. We postulate that CNVs exert a large main effect on psychopathology, but the
nature and degree of psychopathology observed in CNV carriers is multifactorial, with contributions from
additional rare and common genetic variants, as well as environmental factors. Therefore, dissecting the
effects of major CNV hits as well as additional rare and common variants on dimensional measures of
psychopathology can elucidate the combined contribution of genetic mechanisms to psychiatric conditions and
build models of risk prediction. Notably, the presentation and course of psychopathology in the CNVs resemble
these features in idiopathic disorders. Therefore, beyond the specific genetic syndromes investigated, such a
cross-CNV effort will identify convergent risk mechanisms for developmental neuropsychiatric disorders that
are of relevance to the broader population.
 We propose to dissect dimensional measures of psychosis, social-emotional processing and
neurocognition, and their genetic and environmental modifiers, to elucidate the architecture of risk for
neuropsychiatric disorders in CNV carriers. Prospective evaluation with dimensional measures relevant to
neuropsychiatric disorders will be applied to a cohort of 2000 individuals with 22q11.2 and 16p11.2 deletions
and duplications (500 per group) and their relatives as feasible. In addition, categorical psychiatric diagnoses
will be assessed in CNV carriers. Recruitment for prospective phenotyping will leverage existing large cohorts
that carry these reciprocal CNVs, many of whom have already been ascertained and characterized with a
range of phenotypic measures. New whole genome sequencing (WGS) will be performed in CNV carriers that
have not yet been sequenced. We will also utilize existing genetic data from the largest available case-control
samples diagnosed with SZ, ASD, and ADHD in the PGC. Finally, analysis of common variants for a subset of
family members will allow us to complement our primary analysis by exploring models of complex genetic
inheritance in extended pedigrees that carry CNVs. Our ability to conceive such a large scale study capitalizes
on our existing successful collaborations, complementary expertis...

## Key facts

- **NIH application ID:** 9948016
- **Project number:** 5U01MH119736-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** CARRIE E BEARDEN
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $188,643
- **Award type:** 5
- **Project period:** 2019-06-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948016

## Citation

> US National Institutes of Health, RePORTER application 9948016, 3/9 Dissecting the effects of genomic variants on neurobehavioral dimensions in CNVs enriched for neuropsychiatric disorders (5U01MH119736-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948016. Licensed CC0.

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