| Literature DB >> 22889921 |
S E Stewart1, D Yu, J M Scharf, B M Neale, J A Fagerness, C A Mathews, P D Arnold, P D Evans, E R Gamazon, L K Davis, L Osiecki, L McGrath, S Haddad, J Crane, D Hezel, C Illman, C Mayerfeld, A Konkashbaev, C Liu, A Pluzhnikov, A Tikhomirov, C K Edlund, S L Rauch, R Moessner, P Falkai, W Maier, S Ruhrmann, H-J Grabe, L Lennertz, M Wagner, L Bellodi, M C Cavallini, M A Richter, E H Cook, J L Kennedy, D Rosenberg, D J Stein, S M J Hemmings, C Lochner, A Azzam, D A Chavira, E Fournier, H Garrido, B Sheppard, P Umaña, D L Murphy, J R Wendland, J Veenstra-VanderWeele, D Denys, R Blom, D Deforce, F Van Nieuwerburgh, H G M Westenberg, S Walitza, K Egberts, T Renner, E C Miguel, C Cappi, A G Hounie, M Conceição do Rosário, A S Sampaio, H Vallada, H Nicolini, N Lanzagorta, B Camarena, R Delorme, M Leboyer, C N Pato, M T Pato, E Voyiaziakis, P Heutink, D C Cath, D Posthuma, J H Smit, J Samuels, O J Bienvenu, B Cullen, A J Fyer, M A Grados, B D Greenberg, J T McCracken, M A Riddle, Y Wang, V Coric, J F Leckman, M Bloch, C Pittenger, V Eapen, D W Black, R A Ophoff, E Strengman, D Cusi, M Turiel, F Frau, F Macciardi, J R Gibbs, M R Cookson, A Singleton, J Hardy, A T Crenshaw, M A Parkin, D B Mirel, D V Conti, S Purcell, G Nestadt, G L Hanna, M A Jenike, J A Knowles, N Cox, D L Pauls.
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.Entities:
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Year: 2012 PMID： 22889921 PMCID： PMC4218751 DOI： 10.1038/mp.2012.85
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992