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6 results on '"Bienvenu, OJ"'

1. Revealing the complex genetic architecture of obsessive-compulsive disorder using meta-analysis

Author

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)

Subjects
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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2. Whole-genome association analysis of treatment response in obsessive-compulsive disorder

Author

Qin, H, Samuels, JF, Wang, Y, Zhu, Y, Grados, MA, Riddle, MA, Greenberg, BD, Knowles, JA, Fyer, AJ, McCracken, JT, Murphy, DL, Rasmussen, SA, Cullen, BA, Piacentini, J, Geller, D, Stewart, SE, Pauls, D, Bienvenu, OJ, Goes, FS, Maher, B, Pulver, AE, Valle, D, Lange, C, Mattheisen, M, McLaughlin, NC, Liang, K-Y, Nurmi, EL, Askland, KD, Nestadt, G, and Shugart, YY

Subjects
Adult, Male, Obsessive-Compulsive Disorder, Adolescent, Medical and Health Sciences, Linkage Disequilibrium, Genetics, 2.1 Biological and endogenous factors, Humans, Genetic Predisposition to Disease, Aetiology, Polymorphism, Child, Aged, Psychiatry, Human Genome, Psychology and Cognitive Sciences, Membrane Proteins, Genetic Variation, Single Nucleotide, Middle Aged, Biological Sciences, Serious Mental Illness, Mental Health, Treatment Outcome, Serotonin Uptake Inhibitors, Female, Self Report, Selective Serotonin Reuptake Inhibitors, Biotechnology, Genome-Wide Association Study
Abstract

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P

Published
2016

4. Acute fatal myocarditis apparently of viral origin: a case report

Author

Leonard Gl and Bienvenu Oj

Subjects
Myocarditis, business.industry, Myocardium, General Medicine, Middle Aged, medicine.disease, Radiography, Electrocardiography, Virus Diseases, Immunology, Acute Disease, Medicine, Humans, Female, Autopsy, business
Published
1970

5. Copy number variation in obsessive-compulsive disorder and tourette syndrome: a cross-disorder study

Author

McGrath, Lauren M, Yu, Dongmei, Marshall, Christian, Davis, Lea K, Thiruvahindrapuram, Bhooma, Li, Bingbin, Cappi, Carolina, Gerber, Gloria, Wolf, Aaron, Schroeder, Frederick A, Osiecki, Lisa, O'Dushlaine, Colm, Kirby, Andrew, Illmann, Cornelia, Haddad, Stephen, Gallagher, Patience, Fagerness, Jesen A, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Bienvenu, O Joseph, Black, Donald W, Bloch, Michael H, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Cath, Danielle C, Cavallini, Maria C, Chouinard, Sylvain, Coric, Vladimir, Cullen, Bernadette, Delorme, Richard, Denys, Damiaan, Derks, Eske M, Dion, Yves, Rosário, Maria C, Eapen, Valsama, Evans, Patrick, Falkai, Peter, Fernandez, Thomas V, Garrido, Helena, Geller, Daniel, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Grünblatt, Edna, Heiman, Gary A, Hemmings, Sian M J, Herrera, Luis D, Hounie, Ana G, Jankovic, Joseph, Kennedy, James L, King, Robert A, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Lochner, Christine, Lowe, Thomas L, Lyon, Gholson J, Macciardi, Fabio, Maier, Wolfgang, McCracken, James T, McMahon, William, Murphy, Dennis L, Naarden, Allan L, Neale, Benjamin M, Nurmi, Erika, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Reus, Victor I, Richter, Margaret A, Riddle, Mark, Robertson, Mary M, Rosenberg, David, Rouleau, Guy A, Ruhrmann, Stephan, Sampaio, Aline S, Samuels, Jack, Sandor, Paul, Sheppard, Brooke, Singer, Harvey S, Smit, Jan H, Stein, Dan J, Tischfield, Jay A, Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Wang, Ying, Wendland, Jens R, Shugart, Yin Yao, Miguel, Euripedes C, Nicolini, Humberto, Oostra, Ben A, Moessner, Rainald, Wagner, Michael, Ruiz-Linares, Andres, Heutink, Peter, Nestadt, Gerald, Freimer, Nelson, Petryshen, Tracey, Posthuma, Danielle, Jenike, Michael A, Cox, Nancy J, Hanna, Gregory L, Brentani, Helena, Scherer, Stephen W, Arnold, Paul D, Stewart, S Evelyn, Mathews, Carol A, Knowles, James A, Cook, Edwin H, Pauls, David L, Wang, Kai, Scharf, Jeremiah M, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, University of Zurich, Scharf, Jeremiah M, Leerstoel Hout, Sub String Theory Cosmology and ElemPart, Experimental psychopathology, Clinical Genetics, Child and Adolescent Psychiatry / Psychology, Artificial intelligence, Complex Trait Genetics, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Functional Genomics, AIMMS, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, ANS - Amsterdam Neuroscience, Adult Psychiatry, APH - Amsterdam Public Health, Netherlands Institute for Neuroscience (NIN), Mcgrath, Lm, Yu, D, Marshall, C, Davis, Lk, Thiruvahindrapuram, B, Li, B, Cappi, C, Gerber, G, Wolf, A, Schroeder, Fa, Osiecki, L, O'Dushlaine, C, Kirby, A, Illmann, C, Haddad, S, Gallagher, P, Fagerness, Ja, Barr, Cl, Bellodi, Laura, Benarroch, F, Bienvenu, Oj, Black, Dw, Bloch, Mh, Bruun, Rd, Budman, Cl, Camarena, B, Cath, Dc, Cavallini, Mc, Chouinard, S, Coric, V, Cullen, B, Delorme, R, Denys, D, Derks, Em, Dion, Y, Rosário, Mc, Eapen, V, Evans, P, Falkai, P, Fernandez, Tv, Garrido, H, Geller, D, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Grünblatt, E, Heiman, Ga, Hemmings, Sm, Herrera, Ld, Hounie, Ag, Jankovic, J, Kennedy, Jl, King, Ra, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Lochner, C, Lowe, Tl, Lyon, Gj, Macciardi, F, Maier, W, Mccracken, Jt, Mcmahon, W, Murphy, Dl, Naarden, Al, Neale, Bm, Nurmi, E, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Reus, Vi, Richter, Ma, Riddle, M, Robertson, Mm, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Tischfield, Ja, Vallada, H, Veenstra VanderWeele, J, Walitza, S, Wang, Y, Wendland, Jr, Shugart, Yy, Miguel, Ec, Nicolini, H, Oostra, Ba, Moessner, R, Wagner, M, Ruiz Linares, A, Heutink, P, Nestadt, G, Freimer, N, Petryshen, T, Posthuma, D, Jenike, Ma, Cox, Nj, Hanna, Gl, Brentani, H, Scherer, Sw, Arnold, Pd, Stewart, Se, Mathews, Ca, Knowles, Ja, Cook, Eh, Pauls, Dl, Wang, K, Scharf, J. M., Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Mental health

Subjects
Oncology, Male, medicine.medical_specialty, diagnosis [Tourette Syndrome], Adolescent, DNA Copy Number Variations, Genome-wide association study, 610 Medicine & health, Tourette syndrome, Polymorphism, Single Nucleotide, behavioral disciplines and activities, Article, 2738 Psychiatry and Mental Health, SDG 3 - Good Health and Well-being, Obsessive compulsive, Genetic etiology, Internal medicine, mental disorders, Developmental and Educational Psychology, medicine, Humans, Genetic Predisposition to Disease, genetics, Copy-number variation, ddc:610, Genetics, genetics [Obsessive-Compulsive Disorder], 3204 Developmental and Educational Psychology, copy number variation, 10058 Department of Child and Adolescent Psychiatry, medicine.disease, 16p13.11, Diagnostic and Statistical Manual of Mental Disorders, obsessive-compulsive disorder, Psychiatry and Mental health, genetics [Tourette Syndrome], Schizophrenia, Autism, Female, Psychology, Genome-Wide Association Study, diagnosis [Obsessive-Compulsive Disorder]
Abstract

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (

Published
2014
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6. Partitioning the heritability of Tourette syndrome and obsessive compulsive disorder reveals differences in genetic architecture

Author

Patrick Evans, Jay A. Tischfield, Anuar Konkashbaev, Richard Delorme, Sandra Catalina Mesa Restrepo, Margaret A. Richter, Gregory L. Hanna, Allan L. Naarden, Michele T. Pato, Jian Yang, Denise A. Chavira, Damiaan Denys, Paul Sandor, Michael A. Jenike, Sian M. J. Hemmings, Paul D. Arnold, Stephan Ruhrmann, H.G.M. Westenberg, Yves Dion, Cathy L. Barr, Andres Ruiz-Linares, Brooke Sheppard, Leonhard Lennertz, Eske M. Derks, Lauren M. McGrath, Barbara Kremeyer, Marion Leboyer, Victor I. Reus, Cornelia Illmann, S. Evelyn Stewart, Dan J. Stein, Ana Gabriela Hounie, James T. McCracken, R. Kurlan, Chunyu Liu, Aline S. Sampaio, Thomas L. Lowe, Benjamin M. Neale, Yehuda Pollak, Desmond Campbell, Fabio Macciardi, Mary M. Robertson, Benjamin D. Greenberg, Ben A. Oostra, Rainald Moessner, Gary A. Heiman, Nuria Lanzagorta, Sylvain Chouinard, Rianne M. Blom, Karin Egberts, Carlos N. Pato, David V. Conti, Carol A. Mathews, Ying Wang, Marco A. Grados, Julio C. Cardona Silgado, S. Hong Lee, H. Müller, Eric R. Gamazon, Humberto Nicolini, Jan Smit, Euripedes Constantino Miguel, Jens R. Wendland, Cathy L. Budman, Laura Bellodi, Danielle Posthuma, Jubel Morgan, David R. Rosenberg, John Piacentini, Hans J. Grabe, Mark A. Riddle, Beatriz Camarena, Naomi R. Wray, Eric Strengman, Dennis L. Murphy, Simon Girard, Christine Lochner, Ruth D. Bruun, Joseph Jankovic, Edwin H. Cook, William M. McMahon, Scott L. Rauch, James F. Leckman, Peter Falkai, Fortu Benarroch, Christopher K. Edlund, Gabriel Bedoya Berrío, Homero Vallada, Susanne Walitza, Nelson B. Freimer, Stephen A. Haddad, Yin Yao Shugart, Danielle C. Cath, Nancy J. Cox, Varda Gross-Tsur, Guy A. Rouleau, Bernadette Cullen, Michael H. Bloch, Dieter Deforce, David L. Pauls, Thomas V. Fernandez, Roel A. Ophoff, Filip Van Nieuwerburgh, Gerald Nestadt, Dongmei Yu, Helena Garrido, Robert A. King, James L. Kennedy, Clare L. Keenan, Lisa Osiecki, Jack Samuels, Jeremy Veenstra-VanderWeele, Ana V. Valencia Duarte, James A. Knowles, Patience J. Gallagher, Carolina Cappi, Maria Conceição do Rosário, Andrew J. Pakstis, Christopher Pittenger, Michael Wagner, Jeremiah M. Scharf, Daniel A. Geller, Vladimir Coric, Tobias J. Renner, Oscar J. Bienvenu, Roxana Romero, William Cornejo Ochoa, Peter Heutink, Lea K. Davis, Harvey S. Singer, Maria Cristina Cavallini, Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, Department of Psychiatry and Mental Health, Faculty of Health Sciences, Univ Chicago, Harvard Univ, Broad Inst Harvard & MIT, Univ Amsterdam, Massachusetts Gen Hosp, Univ Queensland, Univ Hlth Network, Hosp Sick Children, Univ Vita Salute San Raffaele, Hadassah Hebrew Univ Med Ctr, Univ Pontificia Bolivariana, Johns Hopkins Univ, Yale Univ, North Shore Long Isl Jewish Med Ctr, NYU Med Ctr, North Shore Long Isl Jewish Hlth Syst, Hofstra Univ, Inst Nacl Psiquiatria Ramon de la Fuente Muniz, UCL, Univ Hong Kong, Universidade de São Paulo (USP), Vrije Univ Amsterdam, Univ Utrecht, Altrecht Acad Anxiety Ctr, Univ Milan, Univ Calif Los Angeles, Univ Calif San Diego, Univ Montreal, Univ Illinois, Univ Ghent, Inst Pasteur, French Natl Sci Fdn, Hop Robert Debre, Univ Wurzburg, Univ Munich, Univ Med Greifswald, Butler Hosp, Shaare Zedek Med Ctr, Rutgers State Univ, Univ Stellenbosch, Baylor Coll Med, Ctr Addict & Mental Hlth, Univ Toronto, Overlook Hosp, Carracci Med Grp, Inst Mondor Rech Biomed, Univ Bonn, Univ Calif San Francisco, UCI, Univ Utah, NIMH Intramural Res Program, Med City Dallas Hosp, Univ Med Ctr, Univ So Calif, Partners Psychiat & McLean Hosp, Sunnybrook Hlth Sci Ctr, St George Hosp, Sch Med, Hosp Nacl Ninos Dr Carlos Saenz Herrera, Universidade Federal de São Paulo (UNIFESP), Wayne State Univ, Detroit Med Ctr, McGill Univ, Univ Cologne, Universidade Federal da Bahia (UFBA), Youthdale Treatment Ctr, Johns Hopkins Univ Sch Med, Univ Cape Town, Univ Med Ctr Utrecht, Vanderbilt Univ, Univ Zurich, Inst Royal Netherlands Acad Arts & Sci NIN KNAW, Natl Inst Genom Med SAP, Vrije Univ Amsterdam Med Ctr, Erasmus Univ, Univ Michigan, German Ctr Neurodegenerat Dis, Erasmus MC, Univ British Columbia, Brigham & Womens Hosp, Davis, Lk, Yu, D, Keenan, Cl, Gamazon, Er, Konkashbaev, Ai, Derks, Em, Neale, Bm, Yang, J, Lee, Sh, Evans, P, Barr, Cl, Bellodi, Laura, Benarroch, F, Berrio, Gb, Bienvenu, Oj, Bloch, Mh, Blom, Rm, Bruun, Rd, Budman, Cl, Camarena, B, Campbell, D, Cappi, C, Cardona Silgado, Jc, Cath, Dc, Cavallini, Mc, Chavira, Da, Chouinard, S, Conti, Dv, Cook, Eh, Coric, V, Cullen, Ba, Deforce, D, Delorme, R, Dion, Y, Edlund, Ck, Egberts, K, Falkai, P, Fernandez, Tv, Gallagher, Pj, Garrido, H, Geller, D, Girard, Sl, Grabe, Hj, Grados, Ma, Greenberg, Bd, Gross Tsur, V, Haddad, S, Heiman, Ga, Hemmings, Sm, Hounie, Ag, Illmann, C, Jankovic, J, Jenike, Ma, Kennedy, Jl, King, Ra, Kremeyer, B, Kurlan, R, Lanzagorta, N, Leboyer, M, Leckman, Jf, Lennertz, L, Liu, C, Lochner, C, Lowe, Tl, Macciardi, F, Mccracken, Jt, Mcgrath, Lm, Mesa Restrepo, Sc, Moessner, R, Morgan, J, Muller, H, Murphy, Dl, Naarden, Al, Ochoa, Wc, Ophoff, Ra, Osiecki, L, Pakstis, Aj, Pato, Mt, Pato, Cn, Piacentini, J, Pittenger, C, Pollak, Y, Rauch, Sl, Renner, Tj, Reus, Vi, Richter, Ma, Riddle, Ma, Robertson, Mm, Romero, R, Rosàrio, Mc, Rosenberg, D, Rouleau, Ga, Ruhrmann, S, Ruiz Linares, A, Sampaio, A, Samuels, J, Sandor, P, Sheppard, B, Singer, H, Smit, Jh, Stein, Dj, Strengman, E, Tischfield, Ja, Valencia Duarte, Av, Vallada, H, Van Nieuwerburgh, F, Veenstra Vanderweele, J, Walitza, S, Wang, Y, Wendland, Jr, Westenberg, Hg, Shugart, Yy, Miguel, Ec, Mcmahon, W, Wagner, M, Nicolini, H, Posthuma, D, Hanna, Gl, Heutink, P, Denys, D, Arnold, Pd, Oostra, Ba, Nestadt, G, Freimer, Nb, Pauls, Dl, Wray, Nr, Stewart, Se, Mathews, Ca, Knowles, Ja, Cox, Nj, Scharf, Jm, Functional Genomics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Davis, Lea K, Yu, Dongmei, Keenan, Clare L, Gamazon, Eric R, Lee, S Hong, Scharf, Jeremiah M, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Other departments, ANS - Amsterdam Neuroscience, APH - Amsterdam Public Health, Adult Psychiatry, and Graduate School

Subjects
Cancer Research, Obsessive-Compulsive Disorder, COMPLEX DISEASES, Genome-wide association study, heritability, Genome-wide association studies, neurobehavioral disorders, COMMON SNPS, 0302 clinical medicine, Gene Frequency, Missing heritability problem, MISSING HERITABILITY, Cerebellum, Heritability of autism, BRAIN, Genetics (clinical), Genetics, ddc:616, Genetics & Heredity, 0303 health sciences, Chromosome 15, humanities, FAMILY, obsessive-compulsive disorder, genetics [Tourette Syndrome], Phenotype, NEUROPSYCHIATRIC DISORDERS, GENÔMICA, Research Article, EXPRESSION, lcsh:QH426-470, SNP, Biology, Quantitative trait locus, Genome-wide Complex Trait Analysis, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Chromosomes, TIC DISORDERS, 03 medical and health sciences, Quantitative Trait, Heritable, mental disorders, genetic risk factors, Humans, ddc:610, AUTISM, Variant genotypes, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, genetics [Obsessive-Compulsive Disorder], Tourette syndrome, Parietal lobe, Biology and Life Sciences, Heritability, Genetic architecture, Minor allele frequency, Trastorno Obsesivo Compulsivo, lcsh:Genetics, pathology [Obsessive-Compulsive Disorder], genetic variation, pathology [Tourette Syndrome], Síndrome de Tourette, 030217 neurology & neurosurgery, GILLES, Genome-Wide Association Study, Tourette Syndrome
Abstract

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures., Author Summary Family and twin studies have shown that genetic risk factors are important in the development of Tourette Syndrome (TS) and obsessive compulsive disorder (OCD). However, efforts to identify the individual genetic risk factors involved in these two neuropsychiatric disorders have been largely unsuccessful. One possible explanation for this is that many genetic variations scattered throughout the genome each contribute a small amount to the overall risk. For TS and OCD, the genetic architecture (characterized by the number, frequency, and distribution of genetic risk factors) is presently unknown. This study examined the genetic architecture of TS and OCD in a variety of ways. We found that rare genetic changes account for more genetic risk in TS than in OCD; certain chromosomes contribute to OCD risk more than others; and variants that influence the level of genes expressed in two regions of the brain can account for a significant amount of risk for both TS and OCD. Results from this study might help in determining where, and what kind of variants are individual risk factors for TS and OCD and where they might be located in the human genome.

Published
2013
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