# Integrating neuroimaging and brain gene expression for functional characterization of psychiatric GWAS

> **NIH NIH R21** · MCLEAN HOSPITAL · 2020 · $451,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Mental disorders are complex, debilitating health conditions, yet the neurobiological causes and
pathophysiological mechanisms underlying these disorders are not well understood. The emergence of large-
scale genome-wide association studies (GWAS) has enabled identification of significant, reliable genetic
associations to mental disorders. However, it has been difficult to translate GWAS loci into specific causal driver
variants/genes to extract mechanistic insights for identifying actionable targets for therapeutic interventions.
Neurobiological intermediate phenotypes (NBIPs) are invaluable in understanding the brain’s structural and
functional correlates of elevated risk of psychopathology, although the underlying processes and molecular
mechanisms for observed NBIPs are elusive. Recent advances in genetic-based imputation now allow one to
infer genetically-regulated portions of intermediate phenotypes from genome-wide genotype data. Our research
team has successfully employed brain-specific transcriptomic imputation approaches across mental disorders to
identify novel genes and pathways of risk.
In this proposal, we seek to increase the biological resolution of the link between neuroimaging genetics and
psychiatric genetics by creating novel polygenic models of multimodal neuroimaging based on brain-specific
gene expression that can be applied to psychiatric GWAS. In Aim 1, we will generate brain transcriptomic
predictive models of multimodal neuroimaging and replicate them in independent datasets. In Aim 2, we will
conduct Imaging Transcriptome-wide Association Studies (ITWAS) to identify neuroimaging associations with
mental disorders at a brain-specific gene-level and distinguish the causal ones. Our integrative analyses will
enhance our understanding of NBIPs and mental disorder risk; thus, they will provide mechanistic insights that
may drive identification of novel diagnostic, trans-diagnostic and treatment approaches.

## Key facts

- **NIH application ID:** 10057769
- **Project number:** 1R21MH121909-01A1
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Nikolaos Daskalakis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $451,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057769

## Citation

> US National Institutes of Health, RePORTER application 10057769, Integrating neuroimaging and brain gene expression for functional characterization of psychiatric GWAS (1R21MH121909-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057769. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*