Genetics and Epigenetics of Obsessive-Compulsive Disorder and related endophenotypes

强迫症（Obsessive-Compulsive Disorder， OCD）是一种致残性精神疾病，具有高患病率和高遗传性。更好地了解强迫症的分子遗传基础可能会带来新的治疗方法。在dfg项目“强迫症的内在表型”中，我们收集了500多名强迫症患者、一级亲属和健康对照者的详细表型信息（症状维度；发病、病程和治疗；压力和其他环境暴露；认知、结构和功能MRI、脑电图）。我们证实了几种假定的内表型是家族性的（例如，伤害避免、眼跳变异性）。从所有参与者中抽取血液（90%）或唾液（10%），并且已经获得了全基因组SNP数据。在这里，我们应用详细的遗传和表观遗传（DNA甲基化）分析这个深度表型样本，结合假设驱动和约束发现方法。例如，从现有的全基因组关联研究中得出的强迫症的多基因风险评分，将与最强大的强迫症内表型相关联。新的、遗传信息丰富的表观遗传学分析有望揭示具有差异甲基化和表达的基因。已建立的国际合作可以广泛和可持续地使用数据，交换最新的生物信息学工具，并获得样品以进行复制和后续结果。

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.