1. Genome-wide association study of obsessive-compulsive disorder
- Author
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Helena Garrido, Richard O'Brien, Michael H. Bloch, David L. Pauls, M. Van Der Brug, Anna Tikhomirov, Andrew B. Singleton, Susanne Walitza, Benjamin M. Neale, Patrick Evans, Rianne M. Blom, Mina Ryten, James L. Kennedy, Christopher Pittenger, C. Illman, Amin Azzam, Stephen A. Haddad, Gregory L. Hanna, Michele T. Pato, D. Rosenberg, Maurizio Turiel, Stephan Ruhrmann, Peter Falkai, Nuria Lanzagorta, Richard Delorme, D. G. Hernandez, Leonhard Lennertz, Abby J. Fyer, M Conceição do Rosário, Euripedes Constantino Miguel, John Hardy, Carlos N. Pato, Francesca Frau, Hans-Jörgen Grabe, Daniele Cusi, Alan B. Zonderman, Dieter Deforce, Peter Heutink, Brooke Sheppard, Jacquelyn Crane, Dongmei Yu, Danielle C. Cath, Rainald Moessner, Nancy J. Cox, Shaun Purcell, James A. Knowles, Daniel B. Mirel, Aline S. Sampaio, D. L. Murphy, R. Johnson, Jens R. Wendland, David V. Conti, Carolina Cappi, Paula Umaña, Marco A. Grados, Dan J. Stein, J. R. Gibbs, Humberto Nicolini, Anna Pluzhnikov, Denise A. Chavira, F. Van Nieuwerburgh, Valsamma Eapen, Lisa Osiecki, Christine Lochner, Juan C. Troncoso, Jeremy Veenstra-VanderWeele, Mark A. Riddle, Michael Wagner, Jeremiah M. Scharf, Beatriz Camarena, Edwin H. Cook, Ana Gabriela Hounie, Daniah Trabzuni, Donald W. Black, Scott L. Rauch, Marion Leboyer, Andrew Crenshaw, S. E. Stewart, Roel A. Ophoff, Dianne M. Hezel, Damiaan Denys, Gerald Nestadt, Melissa Parkin, Karin Egberts, Colin Smith, Anuar Konkashbaev, Danielle Posthuma, Vladimir Coric, James F. Leckman, Eric Strengman, Jack Samuels, Tobias J. Renner, Michael E. Weale, L. Ferrucci, Mark R. Cookson, Laura Bellodi, Oscar J. Bienvenu, C. Mayerfeld, Christopher K. Edlund, Youfa Wang, Robert Walker, Dan L. Longo, Maria Cristina Cavallini, James T. McCracken, Jesen Fagerness, H. R. Zielke, Homero Vallada, Chunyu Liu, Bernadette Cullen, Carol A. Mathews, Sian M. J. Hemmings, Allissa Dillman, E. Voyiaziakis, Fabio Macciardi, Eduardo Fournier, Benjamin D. Greenberg, Eric R. Gamazon, S. Arepalli, Margaret A. Richter, Bryan J. Traynor, Michael A. Jenike, J.H. Smit, M. A. Nalls, Lauren M. McGrath, Paul D. Arnold, H.G.M. Westenberg, W. Maier, Other departments, ANS - Amsterdam Neuroscience, Adult Psychiatry, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Netherlands Institute for Neuroscience (NIN), Human genetics, Psychiatry, NCA - Brain mechanisms in health and disease, and NCA - Neurobiology of mental health
- Subjects
Parents ,Obsessive-Compulsive Disorder ,OCD COLLABORATIVE GENETICS ,SLC1A1 ,Genome-wide association study ,genomic ,0302 clinical medicine ,Polymorphism (computer science) ,TRANSPORTER GENE ,GWAS ,SNPS ,Genetics ,QUANTITATIVE TRAIT LOCI ,0303 health sciences ,biology ,Frontal Lobe ,obsessive-compulsive disorder ,Psychiatry and Mental health ,EXPRESSION ,Quantitative Trait Loci ,TWIN ,Nerve Tissue Proteins ,Single-nucleotide polymorphism ,Quantitative trait locus ,Polymorphism, Single Nucleotide ,Article ,White People ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,SDG 17 - Partnerships for the Goals ,DLGAP ,Genetic variation ,mental disorders ,LINKAGE ,Humans ,SNP ,Genetic Predisposition to Disease ,Molecular Biology ,FAMILY-BASED ASSOCIATION ,030304 developmental biology ,Biology and Life Sciences ,neurodevelopmental disorder ,SAP90-PSD95 Associated Proteins ,Case-Control Studies ,REPLICATION ,Expression quantitative trait loci ,biology.protein ,genetic ,030217 neurology & neurosurgery ,Genome-Wide Association Study - 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(-6) and P = 3.44 x 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 x 10(-8). However, when trios were meta-analyzed with the case-control samples, the P-value for this variant was 3.62 x 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.
- Published
- 2013