# Utilizing circRNA transcriptomics for functional characterization of psychiatric GWAS

> **NIH NIH R21** · MCLEAN HOSPITAL · 2024 · $246,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Psychiatric disorders pose intricate challenges to individuals’ well-being, with their underlying
molecular causes and pathophysiological mechanisms remaining elusive. Genome-wide
association studies (GWAS) have provided valuable insights into the genetic associations of
psychiatric disorders. However, translating these associations into specific causal driver variants
and genes to unravel the underlying molecular mechanisms remains a significant challenge.
Recent advancements in genetic-based imputation have enabled the inference of genetically-
regulated components of trascriptomics from genome-wide genotype data. Our research team
has successfully utilized brain-specific transcriptomic imputation approaches across psychiatric
disorders to identify novel genes and pathways associated with risk. Here, we aim to further
enhance our understanding of psychiatric disorders by performing transcriptome-wide
association studies (TWAS) on circular RNAs (circRNA) transcriptomics. CircRNAs are formed
through back splicing and exhibit functional importance. Their unique circular structure and
enhanced stability make them intriguing candidates for studying gene expression regulation in
physiological and pathological conditions. However, their involvement in psychiatric disorders is
understudied and their integration with GWAS studies remains unexplored. In Aim 1, we will
construct genetically regulated circRNA expression models using RNAseq ribo-depleted
libraries of postmortem brain tissues, encompassing diverse ancestries and multiple brain
regions. In Aim 2, we will integrate GWAS data with circRNA expression profiles using TWAS to
identify disease-relevant genes and pathways influenced by circRNA dysregulation. This
integrative approach will enhance our understanding of the molecular mechanisms underlying
psychiatric disorders and provide valuable insights into the functional implications of circRNA
dysregulation. Ultimately, this research has the potential to transform our understanding of the
molecular basis of psychiatric disorders and pave the way for precision medicine strategies in
psychiatric care.

## Key facts

- **NIH application ID:** 10869048
- **Project number:** 1R21MH136479-01
- **Recipient organization:** MCLEAN HOSPITAL
- **Principal Investigator:** Nikolaos Daskalakis
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $246,000
- **Award type:** 1
- **Project period:** 2024-04-05 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869048

## Citation

> US National Institutes of Health, RePORTER application 10869048, Utilizing circRNA transcriptomics for functional characterization of psychiatric GWAS (1R21MH136479-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10869048. Licensed CC0.

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