Dataset Information

Genome-wide association study of obsessive-compulsive disorder.

ABSTRACT: Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 ancestry-matched controls and 400 complete trios remained, with a common set of 469,410 autosomal and 9657 X-chromosome single nucleotide polymorphisms (SNPs). Ancestry-stratified case-control association analyses were conducted for three genetically-defined subpopulations and combined in two meta-analyses, with and without the trio-based analysis. In the case-control analysis, the lowest two P-values were located within DLGAP1 (P=2.49 × 10(-6) and P=3.44 × 10(-6)), a member of the neuronal postsynaptic density complex. In the trio analysis, rs6131295, near BTBD3, exceeded the genome-wide significance threshold with a P-value=3.84 × 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 × 10(-5), losing genome-wide significance. Although no SNPs were identified to be associated with OCD at a genome-wide significant level in the combined trio-case-control sample, a significant enrichment of methylation QTLs (P<0.001) and frontal lobe expression quantitative trait loci (eQTLs) (P=0.001) was observed within the top-ranked SNPs (P<0.01) from the trio-case-control analysis, suggesting these top signals may have a broad role in gene expression in the brain, and possibly in the etiology of OCD.

SUBMITTER: Stewart SE

PROVIDER: S-EPMC4218751 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Genome-wide association study of obsessive-compulsive disorder.

Stewart S E SE Yu D D Scharf J M JM Neale B M BM Fagerness J A JA Mathews C A CA Arnold P D PD Evans P D PD Gamazon E R ER Davis L K LK Osiecki L L McGrath L L Haddad S S Crane J J Hezel D D Illman C C Mayerfeld C C Konkashbaev A A Liu C C Pluzhnikov A A Tikhomirov A A Edlund C K CK Rauch S L SL Moessner R R Falkai P P Maier W W Ruhrmann S S Grabe H-J HJ Lennertz L L Wagner M M Bellodi L L Cavallini M C MC Richter M A MA Cook E H EH Kennedy J L JL Rosenberg D D Stein D J DJ Hemmings S M J SM Lochner C C Azzam A A Chavira D A DA Fournier E E Garrido H H Sheppard B B Umaña P P Murphy D L DL Wendland J R JR Veenstra-VanderWeele J J Denys D D Blom R R Deforce D D Van Nieuwerburgh F F Westenberg H G M HG Walitza S S Egberts K K Renner T T Miguel E C EC Cappi C C Hounie A G AG Conceição do Rosário M M Sampaio A S AS Vallada H H Nicolini H H Lanzagorta N N Camarena B B Delorme R R Leboyer M M Pato C N CN Pato M T MT Voyiaziakis E E Heutink P P Cath D C DC Posthuma D D Smit J H JH Samuels J J Bienvenu O J OJ Cullen B B Fyer A J AJ Grados M A MA Greenberg B D BD McCracken J T JT Riddle M A MA Wang Y Y Coric V V Leckman J F JF Bloch M M Pittenger C C Eapen V V Black D W DW Ophoff R A RA Strengman E E Cusi D D Turiel M M Frau F F Macciardi F F Gibbs J R JR Cookson M R MR Singleton A A Hardy J J Crenshaw A T AT Parkin M A MA Mirel D B DB Conti D V DV Purcell S S Nestadt G G Hanna G L GL Jenike M A MA Knowles J A JA Cox N N Pauls D L DL

Molecular psychiatry 20120814 7

Obsessive-compulsive disorder (OCD) is a common, debilitating neuropsychiatric illness with complex genetic etiology. The International OCD Foundation Genetics Collaborative (IOCDF-GC) is a multi-national collaboration established to discover the genetic variation predisposing to OCD. A set of individuals affected with DSM-IV OCD, a subset of their parents, and unselected controls, were genotyped with several different Illumina SNP microarrays. After extensive data cleaning, 1465 cases, 5557 anc ...[more]

PMID: 22889921

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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 of obsessive-compulsive disorder.

Publications

Genome-wide association study of obsessive-compulsive disorder.

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