Genetics and Epigenetics of Obsessive-Compulsive Disorder and related endophenotypes

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Obsessive-Compulsive Disorder (OCD) is a debilitating psychiatric disorder with high prevalence and substantial heritability. Better insight into the molecular genetic underpinnings of OCD could lead to new treatment approaches. Within the DFG-Project „Endophenotypes of Obsessive-Compulsive Disorder" we gathered detailed phenotypic information from over 500 OCD patients, first-degree-relatives, and healthy controls (symptom dimensions; onset, course, and treatment; stress and other environmental exposures; cognition, structural and functional MRI, EEG). We confirmed several assumed endophenotypes as being familial (e.g. Harm Avoidance, saccade variability). Blood (90%) or saliva (10%) were sampled from all participants and genome-wide SNP data are already available. Here we apply for detailed genetic and epigenetic (DNA methylation) analyses of this deeply phenotyped sample, combining hypothesis-driven and constrained discovery approaches. For example, polygenic risk scores of OCD, derived from existing genome-wide association studies, will be linked with the most robust OCD endophenotypes. Novel, genetically informed epigenetic analyses are expected to reveal genes with differential methylation and expression. Established international collaborations allow an extensive and sustainable use of the data, exchange of latest bioinformatics tool, and access to samples for replication and follow-up of results.