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。我们实验室对强迫症及其遗传学的研究已经活跃了10多年，并于2001年成为强迫症多中心遗传学研究的创始地点之一(P.I.：约翰·霍普金斯大学的Gerald Nestadt博士)。这项研究是通过竞争性的NIMH校外拨款申请获得批准的。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上的强迫症遗传学研究为最近向CIDR提交了DNA和表型信息以进行10 cm基因组扫描的这项全国性的多点、全基因组强迫症研究提供了DNA和家庭评估数据(Samuels等人，在印刷中)。 基因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。 在一项这样的研究中，对317名强迫症患者中每个人的70个强迫症症状进行了因子和聚类分析，发现症状的四个因素组显示了与共病精神障碍的特定关系(Hasler等人，2005年)。因此，因子I(攻击性、性、宗教和躯体的强迫症，以及检查强迫)广泛地与焦虑症和抑郁症并存；因子II(对称性、重复、数数和排序/安排强迫)与双相情感障碍和恐慌症/广场恐惧症有关；因子III(污染强迫和清洁强迫)与进食障碍有关。因子I和因子II与早发性强迫症相关。强迫症与其他精神障碍的频繁共存，以及强迫症症状维度与共病障碍之间相对特殊的关联模式，支持了强迫症亚型对这种异质性疾病的遗传学、治疗和其他研究的重要性。

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 its genetics for over 10 years, and in 2001 became one of the founding sites of a multi-center genetic study of OCD (P.I.: Dr. Gerald Nestadt of Johns Hopkins University.) This study was approved via a competitive NIMH extramural grant application. 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, genome-wide study of OCD which recently submitted DNA and phenotypic information to CIDR for a 10cM genome scan (Samuels et al., in press). Gene 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. In one such study, factor and cluster analysis of 70 OCD symptoms rated in each of the 317 patients with OCD revealed a four factor grouping of symptoms which showed specific relationships to comorbid psychiatric disorders (Hasler et al., 2005). Thus, Factor I (aggressive, sexual, religious and somatic obsessions, and checking compulsions) was broadly associated with comorbid anxiety disorders and depression; Factor II (obsessions of symmetry, and repeating, counting and ordering/arranging compulsions) with bipolar disorders and panic disorder/agoraphobia; and Factor III (contamination obsessions and cleaning compulsions) with eating disorders. Factors I and II were associated with early onset OCD. The frequent co-occurrence of OCD with other psychiatric disorders and the relatively specific association patterns between OCD symptom dimensions and comorbid disorders support the importance of OCD subtyping for genetic, treatment, and other research studies of this heterogeneous disorder.