학술논문
Genome-wide association study of obsessive-compulsive disorder
Document Type
Academic Journal
Author
Stewart, S E; Yu, D; Scharf, J M; Neale, B M; Fagerness, J A; Mathews, C A; Arnold, P D; Evans, P D; Gamazon, E R; Osiecki, L; McGrath, L; Haddad, S; Crane, J; Hezel, D; Illman, C; Mayerfeld, C; Konkashbaev, A; Liu, C; Pluzhnikov, A; Tikhomirov, A; Edlund, C K; Rauch, S L; Moessner, R; Falkai, P; Maier, W; Ruhrmann, S; Grabe, H-J; Lennertz, L; Wagner, M; Bellodi, L; Cavallini, M C; Richter, M A; Cook, E H, Jr; Kennedy, J L; Rosenberg, D; Stein, D J; Hemmings, S MJ; Lochner, C; Azzam, A; Chavira, D A; Fournier, E; Garrido, H; Sheppard, B; Umaña, P; Murphy, D L; Wendland, J R; Veenstra-VanderWeele, J; Denys, D; Blom, R; Deforce, D; Van Nieuwerburgh, F; Westenberg, H GM; Walitza, S; Egberts, K; Renner, T; Miguel, E C; Cappi, C; Hounie, A G; do Rosário, Conceição M; Sampaio, A S; Vallada, H; Nicolini, H; Lanzagorta, N; Camarena, B; Delorme, R; Leboyer, M; Pato, C N; Pato, M T; Voyiaziakis, E; Heutink, P; Cath, D C; Posthuma, D; Smit, J H; Samuels, J; Bienvenu, O J; Cullen, B; Fyer, A J; Grados, M A; Greenberg, B D; McCracken, J T; Riddle, M A; Wang, Y; Coric, V; Leckman, J F; Bloch, M; Pittenger, C; Eapen, V; Black, D W; Ophoff, R A; Strengman, E; Cusi, D; Turiel, M; Frau, F; Macciardi, F; Gibbs, J R; Cookson, M R; Singleton, A; Hardy, J; Crenshaw, A T; Parkin, M A; Mirel, D B; Conti, D V; Purcell, S; Nestadt, G; Hanna, G L; Jenike, M A; Knowles, J A; Cox, N; Pauls, D L
Source
Molecular Psychiatry. Jul 01, 2013 18(7):788-798
Subject
Language
English
ISSN
1359-4184
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 x 10 and P = 3.44 x 10), 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 x 10. However, when trios were meta-analyzed with the case—control samples, the P-value for this variant was 3.62 x 10, 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.