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

The study is funded by the National Institute of Health (NIH) and led James Joseph Crowley, assistant Professor Department of Genetics University of North Carolina at Chapel Hill. The Norwegian arm of this study is led by professor Gerd Kvale (PI) and associate professor Bjarne Hansen (co-PI), with professor Jan Haavik and associate professor Stian Solem as collaborators.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition that causes enormous human suffering and cost to society. Still, 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.

To realize the same advances for OCD, reserchers from University of North Carolina at Chapel Hill, Haukeland University Hospital in Bergen, Karolinska Institutet in Stockholm and Aarhus University, established a consortium (NORDiC). Though this we aim to 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.

Status: Currently collecting samples to the biobank "Biomarkører ved angst og tvangslidelser". The biobank has been approved by the regional ethics commitee (REK Vest: 2014/75) and Professor Jan Haavik is head of the biobank.

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