The Genetics Of Obsessive Compulsive Disorder In Adults

强迫症(OCD)是一种严重的、可遗传的疾病，终生患病率约占人口的2%。遗传方式尚不清楚，但可能很复杂，涉及多个基因座，影响从小到中等。10多年来，我们实验室一直活跃在强迫症及其遗传学的研究中，并于2001年成为由约翰·霍普金斯大学的杰拉尔德·内斯塔特博士领导的强迫症多中心遗传学研究的创始地点之一。这项研究是通过一项竞争性的NIMH校外拨款申请(MH 502140)批准的。由于越来越多的证据支持遗传因素对强迫症的影响，文献中已经进行了一系列候选基因的关联和连锁研究，但只有一次非常小的全基因组扫描被报道。我们在NIMH IRP中的强迫症遗传学研究为这项全国性的多点、计划的全基因组强迫症研究提供了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。该联盟在2004年7月完成了300个新的受影响的同胞对家庭。该样本将用于来年的连锁和关联分析。基因分型和访谈数据将在这个研究强迫症的研究人员联盟内共享，并最终将根据NIMH指南与科学界共享。此外，在NIMH-IRP中，正在对强迫症先证者的DNA、临床特征和人格特征以及与强迫症相关的疾病进行探索性分析，以评估基因变异的候选状态，并更好地确定家族性强迫症的表型。NIMH-IRP强迫症网站目前已登记并完全查明了816名强迫症患者及其随行家属。其他家庭正处于完成协议要求的不同阶段。在过去的一年中，报道了一种不常见的(0.1%)功能性5-羟色胺转运体错义突变与强迫症之间的关联。去年还观察到和报道了突变基因产物的调节和运输功能的改变。这项议定书的继续将允许扩大强迫症先证者、受影响的兄弟姐妹及其家庭成员的样本。这将增加识别与强迫症和相关的神经精神疾病相关的染色体区域和基因的可能性，包括抽动症、抽动症和阿斯伯格综合症。

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 its 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 genetic contributions to 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. This consortium completed 300 new families with affected sib-pairs in July, 2004. This sample will be used for linkage and association analyses during the coming year. 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, within the NIMH-IRP, 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 816 individuals with OCD and their accompanying 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 was reported during the last year. Altered regulation and transport function of the mutated gene product was also observed and reported during the last year. 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 including Tourette's Syndrome, tics and Asperger's Syndrome.