Clinical description and epigenetic profiling of a new Danish OCD case-control cohort.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric condition involving obsessions/compulsions, with genetic and epigenetic mechanisms implicated in its pathophysiology. We describe a novel Danish case-control cohort (138 cases, 151 controls) designed to investigate epigenetic risk factors for OCD. Mental health assessments included parts of the K-SADS-PL and CYBOCS, alongside clinical and familial histories. Blood genome-wide DNA methylation (DNAm) was profiled using Illumina's EPIC array at birth/adolescence. Epigenome-wide association analyses identified several differentially methylated regions (DMRs) associated with OCD (Šidák-adjusted p < 0.05), including three DMRs replicated at both developmental stages. These were annotated to genes ZFP57 and PIWIL1, previously linked to OCD, and POU6F2, associated with schizophrenia and autism. Direction of DNAm change was consistent across time points. Our data suggests that differences in DNAm levels in genes implicated in mental illness are associated with OCD diagnosis, and that some of these epigenetic signals can be detected both at birth and adolescence.