The Genetics Of Obsessive Compulsive Disorder In Adults

成人强迫症的遗传学

• 批准号: 6970030
• 负责人: DENNIS L MURPHY
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6970030
• 关键词: adult human (21+); behavioral /social science research tag; behavioral genetics; family genetics; genotype; human subject; interview; linkage mapping; neurogenetics; obsessive compulsive disorder; patient oriented research; point mutation; psychobiology; serotonin transporter

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.

强迫症（OCD）是一种严重的，可遗传的疾病，终生患病率约为2％。遗传方式尚不清楚，但可能很复杂，涉及小到中度效应的多个基因座。我们的实验室已经活跃于OCD及其遗传学研究已有10多年了，并于2001年成为由约翰·霍普金斯大学（Johns Hopkins University）的杰拉尔德·内斯塔特（Gerald Nestadt）博士领导的多中心基因研究的创始场所之一。这项研究通过竞争性的NIMH校外赠款应用（MH 502140）批准。由于积累了支持OCD遗传贡献的证据，在文献中已经进行了一系列候选基因的关联和联系研究，但仅报告了一个非常小的OCD基因组扫描。我们在NIMH IRP中的强迫症遗传研究为这项全国多站点，计划的全基因组研究的OCD贡献了DNA和家庭评估数据。 OCD遗传联盟中的所有六个地点都使用了标准化的诊断和其他确定性。该财团于2004年7月完成了300个新家庭，由受影响的SIB对，该样本将在来年进行链接和协会分析。基因型和访谈数据将在研究强迫症的研究人员的联盟中共享，并最终按照NIMH指南与科学界共享。此外，在NIMH-IRP中，对DNA的探索性分析，OCD概率的临床特征和人格特征以及与OCD相关的疾病的探索性分析可用于评估基因变异的候选性状态，并更好地定义家族性OCD表型。 NIMH-IRP OCD网站现在已经招募并完全确定了816名患有强迫症的人及其伴随的家人。其他家庭处于完成协议要求的不同阶段。去年报告了不常见的（0.1％），功能性5-羟色胺转运蛋白传播者的错义突变与OCD之间的关联。去年还观察到了突变基因产物的调节和转运功能的改变。该协议的延续将允许扩展OCD检验样本，受影响的兄弟姐妹对及其家人。这应该增加与OCD及相关神经精神疾病有关的染色体区域和基因的可能性，包括Tourette的综合症，TICS和Asperger's综合征。