# Leveraging sources of heterogeneity to delineate the genetic architecture of major depressive disorder

> **NIH NIH K01** · VIRGINIA COMMONWEALTH UNIVERSITY · 2020 · $182,040

## Abstract

ABSTRACT
Major depressive disorder (MD) is a common psychiatric disorder and a leading cause of disability
worldwide. Twin studies estimate the heritability of MD as ~37%, supporting a complex etiology with
both genetic and environmental factors. Efforts to identify specific genetic variants influencing MD risk
remain a challenge. Genome-wide association studies have identified numerous risk variants for many
complex traits but until recently no replicable genome-wide significant associations had been reported for
DSM-defined MD. This may reflect the extensive clinical and etiological heterogeneity of MD. To date,
there has been little systematic work on addressing heterogeneity in a genetically informed framework.
Here, the candidate proposes a research program aimed at leveraging sources of heterogeneity to increase
the power of molecular genetic analyses of MD, towards identification of genetic variants conferring risk
to MD in general, to specific subtypes and symptoms, as well as comorbid traits. Importantly, this
research will move beyond simple phenotype-genotype association towards providing a deeper
understanding of causal processes underlying MD.
 The overarching goal for this career development award is to integrate dimensional phenotype
assessments with molecular genetic data into comprehensive models of disease risk. Through the support
of a K01, the candidate will acquire and apply advanced training in psychiatric nosology, psychometrics,
bioinformatics, and statistical genetic approaches to research causal mechanisms underlying liability to
MD. By leveraging sources of heterogeneity in a multidisciplinary framework, the candidate's research
program aims to (1) refine the MD phenotype for genetic analyses by developing quantitative indices of
MD liability and symptom dimensions, (2) clarify the genetic architecture by applying aggregate genetic
risk methodologies and moderating effects of the environment, and (3) develop novel methods to model
causality and comorbidity by synthesizing divergent methodologies. Moving forward, the candidate's
long-term career goal is to develop the training and experience needed to execute an independent,
transformative, and federally-funded research programme that will elucidate causal processes underlying
mood disorders and correlated traits, with a particular emphasis on statistical methods development.

## Key facts

- **NIH application ID:** 9960608
- **Project number:** 5K01MH113848-03
- **Recipient organization:** VIRGINIA COMMONWEALTH UNIVERSITY
- **Principal Investigator:** Roseann Elizabeth Peterson
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,040
- **Award type:** 5
- **Project period:** 2018-06-19 → 2021-10-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9960608

## Citation

> US National Institutes of Health, RePORTER application 9960608, Leveraging sources of heterogeneity to delineate the genetic architecture of major depressive disorder (5K01MH113848-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9960608. Licensed CC0.

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