Produção Nacional
Revisado por pares
Genome-wide association study of obsessive-compulsive disorder
2012; Springer Nature; Volume: 18; Issue: 7 Linguagem: Inglês
10.1038/mp.2012.85
ISSN1476-5578
AutoresS. Evelyn Stewart, Dongmei Yu, Jeremiah M. Scharf, Benjamin M. Neale, Jesen Fagerness, Carol A. Mathews, Paul Arnold, Patrick Evans, Eric R. Gamazon, Lisa Osiecki, Lauren M. McGrath, Stephen A. Haddad, Jacquelyn Crane, Dianne M. Hezel, C Illman, C Mayerfeld, Anuar Konkashbaev, Chunyu Liu, Anna Pluzhnikov, А. А. Тихомиров, Christopher K. Edlund, Scott L. Rauch, R. Moessner, Peter Falkai, W. Maier, Stephan Ruhrmann, HJ Grabe, Leonhard Lennertz, Michael Wagner, Laura Bellodi, Maria Cristina Cavallini, Margaret A. Richter, Edwin H. Cook, James L. Kennedy, David Rosenberg, Dan J. Stein, Sian Hemmings, Christine Löchner, Amin Azzam, Denise A. Chavira, Eduardo Fournier, Helena Garrido, Brooke Sheppard, Paula Umaña, Dennis L. Murphy, Jens R. Wendland, Jeremy Veenstra‐VanderWeele, Damiaan Denys, Rianne M. Blom, Dieter Deforce, Filip Van Nieuwerburgh, H.G.M. Westenberg, Susanne Walitza, Karin Egberts, Tobias Renner, Eurípedes C. Miguel, Carolina Cappi, Ana Gabriela Hounie, Maria Conceição do Rosário, Aline S. Sampaio, Homero Vallada, Humberto Nicolini, Nuria Lanzagorta, Beatríz Camarena, Richard Delorme, Marion Leboyer, Carlos N. Pato, Michele T. Pato, Emanuel Voyiaziakis, Peter Heutink, Daniëlle C. Cath, Daniëlle Posthuma, Johannes H. Smit, Jack Samuels, O. Joseph Bienvenu, Bernadette Cullen, Abby J. Fyer, Marco A. Grados, Benjamin D. Greenberg, James T. McCracken, Mark A. Riddle, Ying Wang, Vladimir Coric, James F. Leckman, Michael H. Bloch, Christopher Pittenger, Valsamma Eapen, Donald W. Black, Roel A. Ophoff, E Strengman, Daniele Cusi, Maurizio Turiel, Francesca Frau, Fabìo Macciardi, J. Raphael Gibbs, Mark Cookson, Andrew Singleton, Sampath Arepalli, Mark Cookson, Allissa Dillman, Luigi Ferrucci, J. Raphael Gibbs, D. G. Hernandez, Ralph J. Johnson, Dan L. Longo, Michael A. Nalls, Richard M. O’Brien, Andrew Singleton, Bryan J. Traynor, Juan C. Troncoso, Marcel van der Brug, H. Ronald Zielke, Alan B. Zonderman, John Hardy, John Hardy, Mina Ryten, Cynthia C. Smith, Daniah Trabzuni, Robert Walker, Michael E. Weale, Andrew Crenshaw, Melissa Parkin, Daniel B. Mirel, D V Conti, Shaun Purcell, Gerald Nestadt, Gregory L. Hanna, Michael A. Jenike, James A. Knowles, N J Cox, David L. Pauls,
Tópico(s)Autism Spectrum Disorder Research
ResumoObsessive-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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