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STEWART, S. E; YU, D; MCGRATH, L; HADDAD, S; CRANE, J; HEZEL, D; ILLMAN, C; MAYERFELD, C; KONKASHBAEV, A; LIU, C; PLUZHNIKOV, A; TIKHOMIROV, A; SCHARF, J. M; EDLUND, C. K; RAUCH, S. L; MOESSNER, R; FALKAI, P; MAIER, W; RUHRMANN, S; GRABE, H.-J; LENNERTZ, L; WAGNER, M; BELLODI, L; NEALE, B. M; CAVALLINI, M. C; RICHTER, M. A; COOK, E. H; KENNEDY, J. L; ROSENBERG, D; STEIN, D. J; HEMMINGS, Smj; LOCHNER, C; AZZAM, A; CHAVIRA, D. A; FAGEMESS, J. A; FOURNIER, E; GARRIDO, H; SHEPPARD, B; UMANA, P; MURPHY, D. L; WENDLAND, J. R; VEENSTRA-VANDERWEELE, J; DENYS, D; BLOM, R; DEFORCE, D; MATHEWS, C. A; VAN NIEUWERBURGH, F; WESTENBERG, Hgm; WALITZA, S; EGBERTS, K; RENNER, T; MIGUEL, E. C; CAPPI, C; HOUNIE, A. G; CONCEICAO DO ROSARIO, M; SAMPAIO, A. S; ARNOLD, P. D; EVANS, P. D; GAMAZON, E. R; OSIECKI, L
Molecular psychiatry, 07/2013, Volume: 18, Issue: 7Journal Article
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.
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