Genetics and Epigenetics of Obsessive-Compulsive Disorder and related endophenotypes

强迫症(OCD)是一种发病率高、遗传性强的衰弱精神障碍。更好地了解强迫症的分子遗传学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，我们从500多名强迫症患者、一级亲属和健康对照中收集了详细的表型信息(症状维度；发病、病程和治疗；应激和其他环境暴露；认知、结构和功能磁共振成像，EEG)。我们确认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)。从所有参与者身上采集了血液(90%)或唾液(10%)的样本，已经有了全基因组的SNP数据。在这里，我们应用详细的遗传和表观遗传学(DNA甲基化)分析，结合假设驱动和受限的发现方法，对这个表型很深的样本进行分析。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健的强迫症内表型联系在一起。新颖的、基于遗传信息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。已建立的国际合作允许广泛和可持续地使用数据，交换最新的生物信息学工具，以及获取样本以复制和跟踪结果。

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.