1. Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis
- Author
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nternational Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC), OCD Collaborative Genetics Association Studies (OCGAS): Arnold PD, Askland KD, Barlassina C, Bellodi L, Bienvenu OJ, Black D, Bloch M, Brentani H, Burton CL, Camarena B, Cappi C, Cath D, Cavallini M, Conti D, Cook E, Coric V, Cullen BA, Cusi D, Davis LK, Delorme R, Denys D, Derks E, Eapen V, Edlund C, Erdman L, Falkai P, Figee M, Fyer AJ, Geller DA, Goes FS, Grabe H, Grados MA, Greenberg BD, Grünblatt E, Guo W, Hanna GL, Hemmings S, Hounie AG, Jenicke M, Keenan C, Kennedy J, Khramtsova EA, Konkashbaev A, Knowles JA, Krasnow J, Lange C, Lanzagorta N, Leboyer M, Lennertz L, Li B, Liang KY, Lochner C, Macciardi F, Maher B, Maier W, Marconi M, Mathews CA, Matthesien M, McCracken JT, McLaughlin NC, Miguel EC, Moessner R, Murphy DL, Neale B, Nestadt G, Nestadt P, Nicolini H, Nurmi E, Osiecki L, Pauls DL, Piacentini J, Posthuma D, Pulver AE, Qin HD, Rasmussen SA, Rauch S, Richter MA, Riddle MA, Ripke S, Ruhrmann S, Sampaio AS, Samuels JF, Scharf JM, Shugart YY, Smit J, Stein D, Stewart SE, Turiel M, Vallada H, Veenstra-VanderWeele J, Wagner M, Walitza S, Wang Y, Wendland J, Vulink N, Yu D, Zai G., Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Psychiatry, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Reproduction & Development (AR&D), Human genetics, ANS - Compulsivity, Impulsivity & Attention, Adult Psychiatry, APH - Mental Health, Arnold, Paul D, Askland, Kathleen D, Barlassina, Cristina, Bellodi, Laura, Bienvenu, O. J, Black, Donald, Bloch, Michael, Brentani, Helena, Burton, Christie L, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Conti, David, Cook, Edwin, Coric, Vladimir, Cullen, Bernadette A, Cusi, Danielle, Davis, Lea K, Delorme, Richard, Denys, Damiaan, Derks, Eske, Eapen, Valsamma, Edlund, Christopher, Erdman, Lauren, Falkai, Peter, Figee, Martijn, Fyer, Abigail J, Geller, Daniel A, Goes, Fernando S, Grabe, Han, Grados, Marcos A, Greenberg, Benjamin D, Grünblatt, Edna, Guo, Wei, Hanna, Gregory L, Hemmings, Sian, Hounie, Ana G, Jenicke, Michael, Keenan, Clare, Kennedy, Jame, Khramtsova, Ekaterina A, Konkashbaev, Anuar, Knowles, James A, Krasnow, Janice, Lange, Cristophe, Lanzagorta, Nuria, Leboyer, Marion, Lennertz, Leonhard, Li, Bingbin, Liang, K. y, Lochner, Christine, Macciardi, Fabio, Maher, Brion, Maier, Wolfgang, Marconi, Maurizio, Mathews, Carol A, Matthesien, Manuel, Mccracken, James T, Mclaughlin, Nicole C, Miguel, Euripedes C, Moessner, Rainald, Murphy, Dennis L, Neale, Benjamin, Nestadt, Gerald, Nestadt, Paul, Nicolini, Humberto, Nurmi, Ericka, Osiecki, Lisa, Pauls, David L, Piacentini, John, Posthuma, Danielle, Pulver, Ann E, Qin, H. d, Rasmussen, Steven A, Rauch, Scott, Richter, Margaret A, Riddle, Mark A, Ripke, Stephan, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack F, Scharf, Jeremiah M, Shugart, Yin Yao, Smit, Jan, Stein, Daniel, Stewart, S. Evelyn, Turiel, Maurizio, Vallada, Homero, Veenstra vanderweele, Jeremy, Wagner, Michael, Walitza, Susanne, Wang, Y, Wendland, Jen, Vulink, Nienke, Yu, Dongmei, Zai, Gwyneth, and Netherlands Institute for Neuroscience (NIN)
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0301 basic medicine ,Genetics ,TRANSTORNO OBSESSIVO-COMPULSIVO ,Single-nucleotide polymorphism ,Odds ratio ,Biology ,Heritability ,Confidence interval ,Genetic architecture ,Minor allele frequency ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Psychiatry and Mental health ,030104 developmental biology ,0302 clinical medicine ,Journal Article ,SNP ,SDG 2 - Zero Hunger ,Molecular Biology ,030217 neurology & neurosurgery ,Genetic association - Abstract
Two obsessive-compulsive disorder (OCD) genome-wide association studies (GWASs) have been published by independent OCD consortia, the International Obsessive-Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC) and the OCD Collaborative Genetics Association Study (OCGAS), but many of the top-ranked signals were supported in only one study. We therefore conducted a meta-analysis from the two consortia, investigating a total of 2688 individuals of European ancestry with OCD and 7037 genomically matched controls. No single-nucleotide polymorphisms (SNPs) reached genome-wide significance. However, in comparison with the two individual GWASs, the distribution of P-values shifted toward significance. The top haplotypic blocks were tagged with rs4733767 (P=7.1 × 10(-7); odds ratio (OR)=1.21; confidence interval (CI): 1.12-1.31, CASC8/CASC11), rs1030757 (P=1.1 × 10(-6); OR=1.18; CI: 1.10-1.26, GRID2) and rs12504244 (P=1.6 × 10(-6); OR=1.18; CI: 1.11-1.27, KIT). Variants located in or near the genes ASB13, RSPO4, DLGAP1, PTPRD, GRIK2, FAIM2 and CDH20, identified in linkage peaks and the original GWASs, were among the top signals. Polygenic risk scores for each individual study predicted case-control status in the other by explaining 0.9% (P=0.003) and 0.3% (P=0.0009) of the phenotypic variance in OCGAS and the European IOCDF-GC target samples, respectively. The common SNP heritability in the combined OCGAS and IOCDF-GC sample was estimated to be 0.28 (s.e.=0.04). Strikingly, ∼65% of the SNP-based heritability in the OCGAS sample was accounted for by SNPs with minor allele frequencies of ⩾40%. This joint analysis constituting the largest single OCD genome-wide study to date represents a major integrative step in elucidating the genetic causes of OCD.Molecular Psychiatry advance online publication, 1 August 2017; doi:10.1038/mp.2017.154.
- Published
- 2018
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