# OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment Mechanisms

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $595,175

## Abstract

PROJECT SUMMARY
 In this study we seek to understand how genetic and environmental factors jointly influence both the
risk of developing Obsessive-Compulsive Disorder (OCD) and the outcome of treatment interventions. OCD
and related disorders are of major public health importance owing to their profound personal and societal
costs. Little is known for certain about their etiology, and treatment, detection and prevention strategies are not
optimal or directed by knowledge of pathophysiology. In other psychiatric disorders (e.g., schizophrenia,
bipolar disorder and autism), genomics has begun to deliver fundamental knowledge about genetic
architecture, identify specific loci for biological follow-up and localize pathways altered in disease. We intend to
realize these same advances for OCD by markedly increasing the worldwide sample size for genomic analysis,
in a first step toward elucidating the fundamental biology of this condition.
 Three overlapping areas will be investigated in this project. First, we will collect the world's largest richly
phenotyped sample of OCD cases (N = 10,000). To do this in an efficient and cost-effective manner, we will
take advantage of an ongoing nationwide OCD treatment study in Norway and a network of active OCD clinics
in Sweden. The phenotypes will include a detailed clinical characterization (e.g., comorbidities, symptom
dimensions, treatment response) and links to the Swedish and Norwegian registers, facilitating gene by
environment interaction studies. Second, we will genotype all 10,000 samples on the PsychChip GWAS array
(genotypes for >30,000 matched controls are already available). This will allow us to discover genomic loci
harboring common and rare variation associated with OCD. We will also incorporate a novel comparative
genomic approach to interpret these genomic data, capitalizing on an animal model with high face and
construct validity: canine compulsive disorder. Third, we will calculate individual risk profile scores (GRS) as a
measure of genetic liability to OCD and test for interactions between genetic liability and a range of clinical
(e.g., response to treatment), epidemiological (e.g., paternal age, obstetric complications, early life adversity,
socioeconomic status) and genetic epidemiological (e.g., family history) variables from the Swedish and
Norwegian registers. We expect this study to improve our understanding of the causal mechanisms implicated
in OCD, with a view towards improving clinical outcomes and reducing chronicity and societal costs.

## Key facts

- **NIH application ID:** 10161830
- **Project number:** 5R01MH110427-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** James Joseph Crowley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $595,175
- **Award type:** 5
- **Project period:** 2016-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10161830

## Citation

> US National Institutes of Health, RePORTER application 10161830, OCD: Novel Comparative Genomic Approaches to Identify Disease and Treatment Mechanisms (5R01MH110427-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10161830. Licensed CC0.

---

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