The Genetics Of Obsessive Compulsive Disorder In Adults

强迫症（OCD）是一种严重的遗传性疾病，终生患病率约为人口的2%。遗传方式知之甚少，但可能很复杂，涉及多个小到中等影响的基因座。我们的实验室在强迫症和遗传学研究方面已经活跃了10多年，并于2001年成为由约翰霍普金斯大学的Gerald Nestadt博士领导的强迫症多中心遗传学研究的创始地点之一。本研究通过竞争性NIMH校外资助申请（MH 502140）获得批准。由于支持OCD遗传病因学的证据的积累，已经进行了一系列候选基因的关联和连锁研究并在文献中报道，但是仅报道了一个非常小的OCD全基因组扫描。我们在NIMH IRP中的强迫症遗传研究为这个国家多地点，计划的强迫症全基因组研究提供了DNA和家庭评估数据。 强迫症遗传学联盟内的所有六个地点都在使用标准化的诊断和其他确定方法。预计该联盟将在未来三年内增加300个新的受影响兄弟姐妹家庭。该样本将用于连锁和关联分析。基因型和访谈数据将在这个研究强迫症的研究者联盟中共享，并最终将根据NIMH指南与科学界共享。此外，对强迫症先证者和强迫症相关疾病的DNA、临床特征和人格特征的探索性分析正被用于评估基因变异的候选状态，并更好地定义家族性强迫症表型。NIMH-IRP强迫症网站现已招募并完全确定了541名强迫症患者及其家人（包括14对受影响的兄弟姐妹及其家人）。其他家庭正处于完成方案要求的不同阶段。一种罕见的（0.1%）功能性5-羟色胺转运体错义突变与强迫症和强迫性人格障碍（OCPD）之间的关联今年被报道。观察到突变基因的调节和转运功能改变。 本方案的继续将允许扩大强迫症先证者、受影响的兄弟姐妹对及其家庭成员的样本。这将增加识别与强迫症和相关神经精神疾病相关的染色体区域和基因的可能性。

Obsessive-compulsive disorder (OCD) is a severe, heritable condition with a lifetime prevalence of about two percent of the population. The mode of inheritance is poorly understood but is likely complex, involving multiple loci of small to moderate effect. Our laboratory has been active in studies of OCD and of genetics for over 10 years, and in 2001 became one of the founding sites of a multi-center genetic study of OCD, led by Dr. Gerald Nestadt of Johns Hopkins University. This study was approved via a competitive NIMH extramural grant application (MH 502140). Due to the accumulation of evidence supportive of a genetic etiology of OCD, a series of association and linkage studies of candidate genes has been undertaken and reported in the literature, but only one, very small genome- wide scan of OCD has been reported. Our OCD genetic studies in the NIMH IRP contribute DNA and family evaluation data to this national multi-site, planned genome-wide study of OCD. Standardized diagnostic and other ascertainments are being used by all six sites within the OCD genetics consortium. It is anticipated that this consortium will add 300 new families with affected sib-pairs over the next three years. This sample will be used for linkage and association analyses. Genotypes and interview data will be shared within this consortium of investigators studying OCD and will eventually be shared with the scientific community following NIMH guidelines. In addition, exploratory analyses of DNA, clinical features and personality characteristics of OCD probands and of disorders related to OCD are being used to assess the candidacy status of gene variants and to better define the familial OCD phenotype. The NIMH-IRP OCD site has now enrolled and completely ascertained 541 individuals with OCD and family members (including 14 affected sibling pairs and their family members). Other families are in varying stages of completing the protocol requirements. An association between an uncommon (0.1%), functional serotonin transporter missense mutation and OCD and obsessive compulsive personality disorder (OCPD) was reported this year. Altered regulation and transport function of the mutated gene was observed. Continuation of this protocol will allow expansion of a sample of OCD probands, affected sibling pairs and their family members. This should add to the likelihood of identifying chromosomal regions and genes relevant to OCD and related neuropsychiatric disorders.