# Expanding Genetic Understanding of Depression, Anxiety, and their Treatments

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $706,877

## Abstract

ABSTRACT
 Major depressive disorder (MDD) and anxiety disorders (ANX) are genetically related traits that cause
very substantial morbidity and mortality worldwide. The large, diverse, and actively expanding Veterans Affairs
(VA) Million Veteran Program (MVP) is an ideal setting for study of these problems. We have identified risk loci
for MDD and ANX in large genomewide association studies (GWAS), but the size and power of the MVP
dataset, and other datasets worldwide, continue to grow, and considerable work still needs to be done to
develop and maximize the scientific value of the MVP for these traits, and in relation to other datasets available
worldwide. The MVP sample (currently at >900,000 participants) is continuing to expand, and with more
subjects there will be increased power to map relevant traits, including constituent traits (i.e., social phobia).
Extensive phenotype data are available. MVP data releases for the coming year will include whole genome
sequence (WGS) data that will be available for novel analyses; and array data increasing marker density for
non-European populations. Together, availability of these data presents an enormous opportunity.
 We will make our GWAS data available via dbGAP and make further use of it for the present project
We will conduct gene-discovery analysis and leverage polygenicity to dissect the predisposition to MDD, ANX
(and specific anxiety and anxiety -related disorders and subphenotypes which may have distinct as well as
overlapping genetic risk). We will also study medication response genetics and traits phenotypically associated
with MDD and ANX in the MVP sample, e.g. cardiovascular disease, using approaches that permit testing of
likely causality among these correlated traits (e.g., Mendelian Randomization [MR]). We will use genomic
structural equation modeling (gSEM) to investigate the underlying genetic relationships of ANX, MDD, and
other related psychiatric and medical traits. We will complete polygenic risk score (PRS) analysis within MVP
and with respect to external samples using MVP data. WGS data will facilitate study of rare and structural
variants. As the VA has electronic health record (EHR) data going back to the 1990’s and the MVP has EHR
linkage, longitudinal and repeated measures can be constructed. We will replicate findings in collaboration with
other consortia such as the Psychiatric Genomics Consortium MDD (PGC-MDD) and anxiety (PGC-ANX)
working groups (we participate presently). Considering the MVP and other samples we will be able to access,
we predict that case numbers of both traits will increase 2-3 fold over the next five years, greatly increasing
power for locus discovery and thus for post-GWAS analyses. Finally, we will investigate these traits in non-
European populations including African Americans and Latinx – both particularly well-represented in the MVP
sample -- and other populations. Increased understanding of the underlying genetics of these traits should
ulti...

## Key facts

- **NIH application ID:** 10980010
- **Project number:** 1R01MH133728-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JOEL GELERNTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $706,877
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980010

## Citation

> US National Institutes of Health, RePORTER application 10980010, Expanding Genetic Understanding of Depression, Anxiety, and their Treatments (1R01MH133728-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10980010. Licensed CC0.

---

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