The Genetics Of Obsessive Compulsive Disorder In Adults

强迫症（OCD）是一种严重的遗传性疾病，其终生患病率约为人口的2%。遗传模式尚不清楚，但可能很复杂，涉及多个小到中等影响的位点。我们的实验室在强迫症及其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研究的创始地点之一。本研究通过NIMH校外资助申请（MH 502140）获得批准。由于支持基因对强迫症的贡献的证据的积累，一系列候选基因的关联和连锁研究已经在文献中进行和报道，但只有一个非常小的强迫症全基因组扫描被报道。我们在NIMH IRP中的强迫症遗传研究为这个全国性的多位点、计划的强迫症全基因组研究提供了DNA和家族评估数据。

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.