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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Genome-wide association study of obsessive-compulsive disorder
Molecular Psychiatry, Volume 18, No. 7, Year 2013
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Description
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. © 2013 Macmillan Publishers Limited. All rights reserved.
Authors & Co-Authors
Stewart, S. Evelyn
Unknown Affiliation
Yu, Dongmei
Unknown Affiliation
Scharf, Jeremiah M.
Unknown Affiliation
Neale, Benjamin M.
Unknown Affiliation
Fagerness, Jesen A.
Unknown Affiliation
Mathews, Carol A.
Unknown Affiliation
Arnold, Paul Daniel
Unknown Affiliation
Evans, Patrick
Unknown Affiliation
Gamazon, Eric R.
Unknown Affiliation
Osiecki, Lisa
Unknown Affiliation
McGrath, Lauren M.
Unknown Affiliation
Haddad, Stephen
Unknown Affiliation
Crane, Jacquelyn
Unknown Affiliation
Hezel, Dianne M.
Unknown Affiliation
Illman, C.
Unknown Affiliation
Mayerfeld, Catherine
Unknown Affiliation
Konkashbaev, Anuar I.
Unknown Affiliation
Liu, Chunyu
Unknown Affiliation
Pluzhnikov, Anna
Unknown Affiliation
Tikhomirov, A.
Unknown Affiliation
Edlund, Christopher K.
Unknown Affiliation
Rauch, Scott L.
Unknown Affiliation
Moessner, Rainald
Unknown Affiliation
Falkai, Peter
Unknown Affiliation
Maier, Wolfgang
Unknown Affiliation
Ruhrmann, Stephan
Unknown Affiliation
Grabe, Hans Jörgen
Unknown Affiliation
Lennertz, Leonhard
Unknown Affiliation
Wagner, Michael
Unknown Affiliation
Bellodi, Laura
Unknown Affiliation
Cavallini, Maria C.
Unknown Affiliation
Richter, Margaret A.
Unknown Affiliation
Cook, Edwin H.
Unknown Affiliation
Kennedy, James Lowery
Unknown Affiliation
Rosenberg, David
Unknown Affiliation
Stein, Dan J.
Unknown Affiliation
Joanna Hemmings, Sîan Megan
Unknown Affiliation
Lochner, Christine
Unknown Affiliation
Azzam, A.
Unknown Affiliation
Chavira, D. A.
Unknown Affiliation
Fournier, Eduardo
Unknown Affiliation
Garrido, Helena
Unknown Affiliation
Sheppard, Brooke
Unknown Affiliation
Umaña, P.
Unknown Affiliation
Murphy, Dennis L.
Unknown Affiliation
Wendland, J. R.
Unknown Affiliation
Veenstra-Vanderweele, Jeremy
Unknown Affiliation
Denys, Damiaan A.J.P.
Unknown Affiliation
Blom, R.
Unknown Affiliation
Deforce, Dieter
Unknown Affiliation
Van Nieuwerburgh, Filip C.W.
Unknown Affiliation
Westenberg, Herman G.M.
Unknown Affiliation
Walitza, Susanne
Unknown Affiliation
Egberts, Karin Maria
Unknown Affiliation
Renner, T.
Unknown Affiliation
Miguel, Eurípedes Constantino
Unknown Affiliation
Cappi, Carolina
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Hounie, Ana G.
Unknown Affiliation
Rosário, Maria Conceição Do
Unknown Affiliation
Sampaio, Aline S.
Unknown Affiliation
Vallada, Homero
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Nicolini, Humberto
Unknown Affiliation
Lanzagorta, Nuria
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Camarena, Beatriz
Unknown Affiliation
Delorme, Richard
Unknown Affiliation
Leboyer, Marion
Unknown Affiliation
Pato, Carlos N.
Unknown Affiliation
Pato, Michèle T.
Unknown Affiliation
Voyiaziakis, E.
Unknown Affiliation
Heutink, Peter
Unknown Affiliation
Cath, Daniëlle C.
Unknown Affiliation
Posthuma, Daniëlle
Unknown Affiliation
Smit, Johannes Hendrikus
Unknown Affiliation
Samuels, Jack
Unknown Affiliation
Bienvenu, O. Joseph
Unknown Affiliation
Cullen, Bernadette
Unknown Affiliation
Fyer, A. J.
Unknown Affiliation
Grados, M.
Unknown Affiliation
Greenberg, Benjamin D.
Unknown Affiliation
McCracken, James T.
Unknown Affiliation
Riddle, Mark
Unknown Affiliation
Wang, Youfa
Unknown Affiliation
Coric, Vladimir
Unknown Affiliation
Leckman, James F.
Unknown Affiliation
Bloch, Michael Howard
Unknown Affiliation
Pittenger, Christopher John
Unknown Affiliation
Eapen, Valsamma N.
Unknown Affiliation
Black, Donald W.
Unknown Affiliation
Ophoff, R. A.
Unknown Affiliation
Strengman, Eric
Unknown Affiliation
Cusi, Daniele
Unknown Affiliation
Turiel, Maurizio
Unknown Affiliation
Frau, F.
Unknown Affiliation
MacCiardi, Fabio
Unknown Affiliation
Gibbs, J. Raphael
Unknown Affiliation
Cookson, Mark Robert
Unknown Affiliation
Singleton, Andrew B.
Unknown Affiliation
Arepalli, Sampath K.
Unknown Affiliation
Cookson, Mark R.
Unknown Affiliation
Dillman, Allissa Amanda
Unknown Affiliation
Statistics
Citations: 293
Authors: 100
Affiliations: 60
Identifiers
Doi:
10.1038/mp.2012.85
ISSN:
13594184
e-ISSN:
14765578
Research Areas
Genetics And Genomics
Study Design
Case-Control Study
Study Approach
Quantitative