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The genetics of obsessive-compulsive disorder: a review.

ABSTRACT: Obsessive-compulsive disorder (OCD) is a serious psychiatric disorder that affects approximately 2% of the populations of children and adults. Family aggregation studies have demonstrated that OCD is familial, and results from twin studies demonstrate that the familiality is due in part to genetic factors. Only three genome-wide linkage studies have been completed to date, with suggestive but not definitive results. In addition, over 80 candidate gene studies have been published. Most of these studies have focused on genes in the serotonergic and dopaminergic pathways. Unfortunately, none have achieved genome-wide significance, and, with the exception of the glutamate transporter gene, none have been replicated. Future research will require the collaboration of multidisciplinary teams of investigators to (i) achieve sufficiently large samples of individuals with OCD; (ii) apply the state-of-the-art laboratory techniques; and (iii) perform the bioinformatic analyses essential to the identification of risk loci.

SUBMITTER: Pauls DL

PROVIDER: S-EPMC3181951 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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The genetics of obsessive-compulsive disorder: a review.

Pauls David L DL

Dialogues in clinical neuroscience 20100101 2

Obsessive-compulsive disorder (OCD) is a serious psychiatric disorder that affects approximately 2% of the populations of children and adults. Family aggregation studies have demonstrated that OCD is familial, and results from twin studies demonstrate that the familiality is due in part to genetic factors. Only three genome-wide linkage studies have been completed to date, with suggestive but not definitive results. In addition, over 80 candidate gene studies have been published. Most of these s ...[more]

PMID: 20623920

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Project description:Objective: To evaluate the lifetime prevalence of infectious, inflammatory, and autoimmune disorders in a multisite study of probands with childhood-onset obsessive compulsive disorder (OCD) and their first-degree relatives. Methods: Medical questionnaires were completed by 1401 probands and 1045 first-degree relatives in the OCD Collaborative Genetics Association Study. Lifetime prevalence of immune-related diseases was compared with the highest available population estimate and reported as a point estimate with 95% adjusted Wald interval. Worst-episode OCD severity and symptom dimensions were assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS) and Symptom Checklist (YBOCS-CL). Results: Probands reported higher-than-expected prevalence of scarlet fever (4.0 [3.1-5.2]% vs. 1.0%-2.0%, z?=?1.491, p?<?0.001, n?=?1389), encephalitis or meningitis (1.4 [0.9-2.1]% vs. 0.1%-0.4%, z?=?5.913, p?<?0.001, n?=?1393), rheumatoid arthritis (1.1 [0.6-2.0]% vs. 0.2%-0.4%, z?=?3.416, p?<?0.001, n?=?949) and rheumatic fever (0.6 [0.3-1.2]% vs. 0.1%-0.2%, z?=?3.338, p?<?0.001, n?=?1390), but not systemic lupus erythematosus, diabetes, asthma, multiple sclerosis, psoriasis, or inflammatory bowel disease. First-degree relatives reported similarly elevated rates of scarlet fever, rheumatic fever, and encephalitis or meningitis independent of OCD status. There was no association between worst-episode severity and immune-related comorbidities, although probands reporting frequent ear or throat infections had increased severity of cleaning-/contamination-related symptoms (mean factor score 2.5?±?0.9 vs. 2.3?±?1.0, t?=?3.183, p?=?0.002, n?=?822). Conclusion: These data suggest high rates of streptococcal-related and other immune-mediated diseases in patients with childhood-onset OCD and are consistent with epidemiological studies in adults noting familial clustering. Limitations include potential reporting bias and absence of a control group, underscoring the need for further prospective studies characterizing medical and psychiatric disease clusters and their interactions in children. Such studies may ultimately improve our understanding of OCD pathogenesis and aid in the development of adjunctive immune-modulating therapeutic strategies.

Dataset Information

The genetics of obsessive-compulsive disorder: a review.

Publications

The genetics of obsessive-compulsive disorder: a review.

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