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10多年来一直积极研究强迫症及其遗传学，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杰拉尔德·内斯塔特博士。）本研究通过竞争性NIMH校外资助申请获得批准。由于支持遗传对强迫症的贡献的证据的积累，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强迫症全基因组扫描。我们在NIMH IRP中的OCD遗传研究为这个国家多位点、全基因组OCD研究提供了DNA和家族评估数据，该研究最近向CIDR提交了DNA和表型信息，用于10 cM基因组扫描（Samuels et al.，出版中）。 基因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，在NIMH-IRP中，对OCD先证者和OCD相关疾病的DNA、临床特征和人格特征的探索性分析被用于评估基因变异的候选状态，并更好地定义家族性OCD表型。 在一项这样的研究中，对317名强迫症患者中的每一名评定的70种强迫症症状的因子和聚类分析揭示了症状的四因子分组，其显示出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、宗教和躯体强迫观念，以及检查强迫）与共病焦虑症和抑郁症广泛相关;因子II（对称强迫观念，以及重复、计数和排序/安排强迫）与双相情感障碍和惊恐障碍/广场恐怖症广泛相关;因子III（污染强迫观念和清洁强迫）与进食障碍广泛相关。因子I和因子II与早发性强迫症相关。强迫症与其他精神疾病的频繁共存以及强迫症症状维度与共病疾病之间相对特定的关联模式支持强迫症亚型对这种异质性疾病的遗传、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.