# Chronic pain conditions and internalizing psychopathology, a genetic epidemiology investigation.

> **NIH VA IK2** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

ABSTRACT. Veterans with chronic pain conditions such as migraine headache, fibromyalgia, and irritable
bowel syndrome frequently manifest comorbid internalizing psychiatric conditions such as mood and anxiety
disorders. The comorbidity between chronic pain conditions and internalizing disorders exacerbates the course
of both, contributes to increased opiate use and low quality of life, and leads to worse treatment outcomes.
While twin studies have indicated substantial overlap in genetic and environmental influences between
individual chronic pain conditions and internalizing disorders, progress in identifying specific genetic variants
underlying this relationship has been slow. To date, no studies have evaluated the relationship among chronic
pain conditions and internalizing disorders using molecular genetic methodology, those that allow for the
identification of specific genes, representing a significant knowledge gap in our understanding of the etiology of
these conditions. To address the glaring research gap, the present CDA-2 includes an observational cohort
study using data available from the Million Veteran Program (MVP) to examine the relationship between
chronic pain conditions and internalizing disorders. The MVP represents a unique and powerful resource for
evaluating these relationships through the combination of extensive electronic health record (EHR) and
genome-wide genetic data. Using data from this large and representative sample, the specific aims are to: 1)
derive chronic pain and internalizing disorder phenotypes from EHR; 2) evaluate the genetic overlap between
chronic pain conditions and internalizing disorders using genome-wide association study and linkage
disequilibrium (LD)-score regression; and 3) explore the causal relationships among chronic pain, internalizing
disorders, and opioid use with Mendelian randomization methods. Strengths of the proposal include the use of
large-scale EHR and genetic data to reveal the genetic contributions to the comorbidity among chronic pain
conditions and internalizing disorders, and the evaluation of multiple chronic pain conditions and internalizing
disorders at once. Understanding the shared genetic etiologies between chronic pain conditions and
internalizing disorders as well as potential causal mechanisms will provide targets for advancing therapeutic
intervention and facilitate the progression from genetic epidemiology to personalized medicine.
 The proposed CDA-2 will provide the candidate the training and research opportunities necessary to
advance a model of genetic comorbidity among chronic pain conditions and internalizing disorders and support
her long-term goal of becoming an independent researcher within the VA with a focus on genetic epidemiology
of chronic pain and psychiatric disorders, and the development of precision medicine approaches to the
treatment of Veterans with these conditions. Specific training goals include 1) gaining proficiency in the use of
EHR data f...

## Key facts

- **NIH application ID:** 10595497
- **Project number:** 5IK2CX002107-03
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Marianna Gasperi
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10595497

## Citation

> US National Institutes of Health, RePORTER application 10595497, Chronic pain conditions and internalizing psychopathology, a genetic epidemiology investigation. (5IK2CX002107-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10595497. Licensed CC0.

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