# Functional genomic resource and integrative model of dopaminergic circuitry associated with psychiatric disease

> **NIH NIH U01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $660,307

## Abstract

PROJECT SUMMARY
Great progress has been made in mapping the transcriptome and some its epigenomic determinants of the
adult and developing human cerebral cortex (including alterations in common psychiatric disease) through the
efforts of the PsychENCODE consortium. However, next to nothing, or very little, is known about genomic
regulation in brainstem monoaminergic neurons and their ascending projections into the forebrain, a circuitry
critically involved in the pathophysiology of mood and psychosis spectrum disorders and substance abuse
disorders, among others. The goal of our project is to construct transcriptome and epigenome (incl. 3D
genome/chromosomal conformation) maps for midbrain dopaminergic neurons and for their surrounding non-
neuronal cells, and to assess the relationship to known genetic risk factors for complex mental illness, including
psychosis with substance abuse co-morbidity. We will apply integrative methods for functional analysis of risk
genetic variation and networks, including but not limited to Bayesian network reconstruction and prediction
algorithms of variant causality to identify key drivers of schizophrenia and bipolar disease pathology, and drug
addiction co-morbidity. These methods will simultaneously integrate multiple different dimensions of data: DNA
variation, RNA expression, chromatin accessibility, 3D structure of the genome, known pathway and gene
network information in the context of clinical phenotype data. The fundamental source of data for the project
comes from the current studies on human midbrain functional omics, and the CommonMinds and
PsychENCODE consortia (whole genome sequencing and cortical functional omics data), the Psychiatric
Genomics Consortium and the Million Veterans Project (genetic variation and disease phenotypes). The Million
Veterans Project (MVP) has collected genotyping and phenotypic data from ~700,000 individuals, including a
subgroup of 50,000 veterans diagnosed with SCZ and BD and a larger group of individuals diagnosed with
other neuropsychiatric traits (recurrent depression, suicide and substance abuse). We will make our newly
generated transcriptome and epigenome datasets from adult midbrain, as well as the network and predictive
models, available to the research community in accordance with NIMH data sharing policies.

## Key facts

- **NIH application ID:** 10360606
- **Project number:** 5U01DA048279-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Schahram Akbarian
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $660,307
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360606

## Citation

> US National Institutes of Health, RePORTER application 10360606, Functional genomic resource and integrative model of dopaminergic circuitry associated with psychiatric disease (5U01DA048279-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360606. Licensed CC0.

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