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Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

ABSTRACT: Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples.

SUBMITTER: Mattheisen M

PROVIDER: S-EPMC4231023 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Mattheisen M M Samuels J F JF Wang Y Y Greenberg B D BD Fyer A J AJ McCracken J T JT Geller D A DA Murphy D L DL Knowles J A JA Grados M A MA Riddle M A MA Rasmussen S A SA McLaughlin N C NC Nurmi E L EL Askland K D KD Qin H-D HD Cullen B A BA Piacentini J J Pauls D L DL Bienvenu O J OJ Stewart S E SE Liang K-Y KY Goes F S FS Maher B B Pulver A E AE Shugart Y Y YY Valle D D Lange C C Nestadt G G

Molecular psychiatry 20140513 3

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based sa ...[more]

PMID: 24821223

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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

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Publications

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

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