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1. Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author: Barr, Cathy L., Batterson, James R., Berlin, Cheston, Budman, Cathy L., Coppola, Giovanni, Cox, Nancy J., Darrow, Sabrina, Dion, Yves, Freimer, Nelson B., Grados, Marco A., Greenberg, Erica, Hirschtritt, Matthew E., Huang, Alden Y., Illmann, Cornelia, King, Robert A., Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., McMahon, William M., Neale, Benjamin M., Okun, Michael S., Osiecki, Lisa, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Singer, Harvey S., Smit, Jan H., Sul, Jae Hoon, Androutsos, Christos, Basha, Entela, Farkas, Luca, Fichna, Jakub, Janik, Piotr, Kapisyzi, Mira, Karagiannidis, Iordanis, Koumoula, Anastasia, Nagy, Peter, Puchala, Joanna, Szejko, Natalia, Szymanska, Urszula, Tsironi, Vaia, Apter, Alan, Ball, Juliane, Bodmer, Benjamin, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, Garcia-Delgar, Blanca, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Madruga-Garrido, Marcos, Pellico, Alessandra, Ruhrman, Daphna, Schnell, Jaana, Silvestri, Paola Rosaria, Skov, Liselotte, Steinberg, Tamar, Gloor, Friederike Tagwerker, Turner, Victoria L., Weidinger, Elif, Alexander, John, Aranyi, Tamas, Buisman, Wim R., Buitelaar, Jan K., Driessen, Nicole, Drineas, Petros, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., Nawaz, Muhammad S., Nespoli, Ester, Pagliaroli, Luca, Poelmans, Geert, Pouwels, Petra J.W., Rizzo, Francesca, Veltman, Dick J., van der Werf, Ysbrand D., Widomska, Joanna, Zilhäo, Nuno R., Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Fernandez, Thomas V., Gilbert, Donald L., Hong, Hyun Ju, Ibanez-Gomez, Laura, Kim, Eun-Joo, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L., Maras, Athanasios, Murphy, Tara L., Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, State, Matthew W., Visscher, Frank, Wang, Sheng, Zinner, Samuel H., Tsetsos, Fotis, Topaloudi, Apostolia, Jain, Pritesh, Yang, Zhiyu, Yu, Dongmei, Kolovos, Petros, Tumer, Zeynep, Rizzo, Renata, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Müller-Vahl, Kirsten R., Cath, Danielle C., Boomsma, Dorret I., Wolanczyk, Tomasz, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Padmanabhuni, Shanmukha S., Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Yannaki, Evangelia, Stamatoyannopoulos, John A., Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Mir, Pablo, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Roessner, Veit, Walitza, Susanne, Schrag, Anette, Martino, Davide, Tischfield, Jay A., Heiman, Gary A., Willsey, A. Jeremy, Dietrich, Andrea, Davis, Lea K., Crowley, James J., Mathews, Carol A., Scharf, Jeremiah M., Georgitsi, Marianthi, Hoekstra, Pieter J., and Paschou, Peristera
Published: 2024
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2. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Author: Claudio‐Campos, Karla, Stevens, Daniel, Koo, Sang‐Wahn, Valko, Alexa, Bienvenu, Oscar Joseph, Budman, Cathy B, Cath, Danielle C, Darrow, Sabrina, Geller, Daniel, Goes, Fernando S, Grados, Marco A, Greenberg, Benjamin D, Greenberg, Erica, Hirschtritt, Matthew E, Illmann, Cornelia, Ivankovic, Franjo, King, Robert A, Knowles, James A, Krasnow, Janice, Lee, Paul C, Lyon, Gholson J, McCracken, James T, Robertson, Mary M, Osiecki, Lisa, Riddle, Mark A, Rouleau, Guy, Sandor, Paul, Nestadt, Gerald, Samuels, Jack, Scharf, Jeremiah M, Mathews, Carol A, and Study, for the Tourette Association of America International Consortium for Genetics and the OCD Collaborative Genetics Association
Subjects: Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Brain Disorders, Behavioral and Social Science, Anxiety Disorders, Tourette Syndrome, Neurodegenerative, Serious Mental Illness, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Mental health, Attention Deficit Disorder with Hyperactivity, Comorbidity, Humans, Obsessive-Compulsive Disorder, Tic Disorders, Tics, chronic tics, meta&#8208, analysis, severity, Tourette, Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study, meta-analysis, Human Movement and Sports Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Published: 2021

3. Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Author: Tsetsos, Fotis, Yu, Dongmei, Sul, Jae Hoon, Huang, Alden Y, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M, Hirschtritt, Matthew E, Greenberg, Erica, Muller-Vahl, Kirsten R, Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy A, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L, Grados, Marco A, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, Hinney, Anke, King, Robert A, Fernandez, Thomas V, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L, Rizzo, Renata, Lyon, Gholson J, McMahon, William M, Batterson, James R, Cath, Danielle C, Malaty, Irene A, Okun, Michael S, Berlin, Cheston, Woods, Douglas W, Lee, Paul C, Jankovic, Joseph, Robertson, Mary M, Gilbert, Donald L, Brown, Lawrence W, Coffey, Barbara J, Dietrich, Andrea, Hoekstra, Pieter J, Kuperman, Samuel, Zinner, Samuel H, Wagner, Michael, Knowles, James A, Jeremy Willsey, A, Tischfield, Jay A, Heiman, Gary A, Cox, Nancy J, Freimer, Nelson B, Neale, Benjamin M, Davis, Lea K, Coppola, Giovanni, Mathews, Carol A, Scharf, Jeremiah M, Paschou, Peristera, Tourette Association of America International Consortium for Genetics, Darrow, Sabrina, Kurlan, Roger, Leckman, James F, Smit, Jan H, and Gilles de la Tourette GWAS Replication Initiative
Subjects: Tourette Association of America International Consortium for Genetics, Gilles de la Tourette GWAS Replication Initiative, Tourette International Collaborative Genetics Study, Psychiatric Genomics Consortium Tourette Syndrome Working Group, Neurons, Humans, Tourette Syndrome, Genotype, Genome-Wide Association Study, Mental Health, Genetics, Neurosciences, Human Genome, Brain Disorders, Biotechnology, Neurodegenerative, 2.1 Biological and endogenous factors, Clinical Sciences, Public Health and Health Services, Psychology
Abstract: Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.
Published: 2021

4. Relationship between adverse childhood experiences and symptom severity in adult men with Tourette Syndrome

Author: Yang, Kelly, Essa, Angela, Noriega, Daisy, Yu, Dongmei, Osiecki, Lisa, Gauvin, Caitlin A., Illmann, Cornelia, Bortolato, Marco, Dunn, Erin C., Mathews, Carol A., and Scharf, Jeremiah M.
Published: 2022
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5. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

Author: Yu, Dongmei, Sul, Jae Hoon, Tsetsos, Fotis, Nawaz, Muhammad S, Huang, Alden Y, Zelaya, Ivette, Illmann, Cornelia, Osiecki, Lisa, Darrow, Sabrina M, Hirschtritt, Matthew E, Greenberg, Erica, Muller-Vahl, Kirsten R, Stuhrmann, Manfred, Dion, Yves, Rouleau, Guy, Aschauer, Harald, Stamenkovic, Mara, Schlögelhofer, Monika, Sandor, Paul, Barr, Cathy L, Grados, Marco, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, Hinney, Anke, King, Robert A, Fernandez, Thomas V, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Budman, Cathy L, Rizzo, Renata, Lyon, Gholson J, McMahon, William M, Batterson, James R, Cath, Danielle C, Malaty, Irene A, Okun, Michael S, Berlin, Cheston, Woods, Douglas W, Lee, Paul C, Jankovic, Joseph, Robertson, Mary M, Gilbert, Donald L, Brown, Lawrence W, Coffey, Barbara J, Dietrich, Andrea, Hoekstra, Pieter J, Kuperman, Samuel, Zinner, Samuel H, Luðvigsson, Pétur, Sæmundsen, Evald, Thorarensen, Ólafur, Atzmon, Gil, Barzilai, Nir, Wagner, Michael, Moessner, Rainald, Ophoff, Roel, Pato, Carlos N, Pato, Michele T, Knowles, James A, Roffman, Joshua L, Smoller, Jordan W, Buckner, Randy L, Willsey, A Jeremy, Tischfield, Jay A, Heiman, Gary A, Stefansson, Hreinn, Stefansson, Kári, Posthuma, Danielle, Cox, Nancy J, Pauls, David L, Freimer, Nelson B, Neale, Benjamin M, Davis, Lea K, Paschou, Peristera, Coppola, Giovanni, Mathews, Carol A, and Scharf, Jeremiah M
Subjects: Mental Health, Prevention, Brain Disorders, Human Genome, Neurosciences, Neurodegenerative, Serious Mental Illness, Tourette Syndrome, Genetics, Aetiology, 2.1 Biological and endogenous factors, Case-Control Studies, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Risk Factors, Severity of Illness Index, Tic Disorders, fms-Like Tyrosine Kinase 3, Tourette Association of America International Consortium for Genetics, the Gilles de la Tourette GWAS Replication Initiative, the Tourette International Collaborative Genetics Study, and the Psychiatric Genomics Consortium Tourette Syndrome Working Group, Child Psychiatry, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.
Published: 2019

6. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome

Author: Greenberg, Erica, Tung, Esther S, Gauvin, Caitlin, Osiecki, Lisa, Yang, Kelly G, Curley, Erin, Essa, Angela, Illmann, Cornelia, Sandor, Paul, Dion, Yves, Lyon, Gholson J, King, Robert A, Darrow, Sabrina, Hirschtritt, Matthew E, Budman, Cathy L, Grados, Marco, Pauls, David L, Keuthen, Nancy J, Mathews, Carol A, Scharf, Jeremiah M, and The Tourette Association of America International Consortium for Genetics
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Psychology, Brain Disorders, Tourette Syndrome, Neurodegenerative, Serious Mental Illness, Mental Health, Clinical Research, Anxiety Disorders, Mental health, Child, Comorbidity, Female, Humans, Male, Obsessive-Compulsive Disorder, Prevalence, Self-Injurious Behavior, Surveys and Questionnaires, Trichotillomania, Trichotillomania/hair pulling disorder, Excoriation disorder/skin picking disorder, Tourette syndrome, Obsessive-compulsive disorder, Body-focused repetitive behaviors, Tourette Association of America International Consortium for Genetics, Obsessive–compulsive disorder, Developmental & Child Psychology, Clinical sciences, Applied and developmental psychology, Clinical and health psychology
Abstract: Trichotillomania/hair pulling disorder (HPD) and excoriation/skin picking disorder (SPD) are childhood-onset, body-focused repetitive behaviors that are thought to share genetic susceptibility and underlying pathophysiology with obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We sought to determine the prevalence of DSM-5 HPD and SPD in TS patients, and to identify clinical factors most associated with their co-morbidity with TS. Participants included 811 TS patients recruited from TS specialty clinics for a multi-center genetic study. Patients were assessed using standardized, validated semi-structured interviews. HPD and SPD diagnoses were determined using a validated self-report questionnaire. HPD/SPD prevalence rates were calculated, and clinical predictors were evaluated using regression modeling. 3.8 and 13.0% of TS patients met DSM-5 criteria for HPD and SPD, respectively. In univariable analyses, female sex, OCD, and both tic and obsessive-compulsive symptom severity were among those associated with HPD and/or SPD. In multivariable analyses, only lifetime worst-ever motor tic severity remained significantly associated with HPD. Female sex, co-occurring OCD, ADHD, and motor tic severity remained independently associated with SPD. This is the first study to examine HPD and SPD prevalence in a TS sample using semi-structured diagnostic instruments. The prevalence of HPD and SPD in TS patients, and their association with increased tic severity and co-occurring OCD, suggests that clinicians should screen children with TS and related disorders for HPD/SPD, particularly in females and in those with co-occurring OCD. This study also helps set a foundation for subsequent research regarding HPD/SPD risk factors, pathophysiology, and treatment models.
Published: 2018

7. Autism Spectrum Symptoms in a Tourette's Disorder Sample.

Author: Darrow, Sabrina M, Grados, Marco, Sandor, Paul, Hirschtritt, Matthew E, Illmann, Cornelia, Osiecki, Lisa, Dion, Yves, King, Robert, Pauls, David, Budman, Cathy L, Cath, Danielle C, Greenberg, Erica, Lyon, Gholson J, McMahon, William M, Lee, Paul C, Delucchi, Kevin L, Scharf, Jeremiah M, and Mathews, Carol A
Subjects: Humans, Tourette Syndrome, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity, Comorbidity, Adolescent, Adult, Middle Aged, Child, Female, Male, Young Adult, Autism Spectrum Disorder, Tourette's disorder, attention-deficit/hyperactivity disorder, autism, heritability, obsessive-compulsive disorder, Neurodegenerative, Neurosciences, Clinical Research, Intellectual and Developmental Disabilities (IDD), Attention Deficit Hyperactivity Disorder (ADHD), Autism, Mental Health, Behavioral and Social Science, Pediatric, Brain Disorders, Mental health, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology
Abstract: ObjectiveTourette's disorder (TD) and autism spectrum disorder (ASD) share clinical features and possibly an overlapping etiology. The aims of this study were to examine ASD symptom rates in participants with TD, and to characterize the relationships between ASD symptom patterns and TD, obsessive-compulsive disorder (OCD), and attention-deficit/hyperactivity disorder (ADHD).MethodParticipants with TD (n = 535) and their family members (n =234) recruited for genetic studies reported TD, OCD, and ADHD symptoms and completed the Social Responsiveness Scale Second Edition (SRS), which was used to characterize ASD symptoms.ResultsSRS scores in participants with TD were similar to those observed in other clinical samples but lower than in ASD samples (mean SRS total raw score = 51; SD = 32.4). More children with TD met cut-off criteria for ASD (22.8%) than adults with TD (8.7%). The elevated rate in children was primarily due to high scores on the SRS Repetitive and Restricted Behaviors (RRB) subscale. Total SRS scores were correlated with TD (r = 0.27), OCD (r = 0.37), and ADHD (r = 0.44) and were higher among individuals with OCD symptom-based phenotypes than for those with tics alone.ConclusionHigher observed rates of ASD among children affected by TD may in part be due to difficulty in discriminating complex tics and OCD symptoms from ASD symptoms. Careful examination of ASD-specific symptom patterns (social communication vs. repetitive behaviors) is essential. Independent of ASD, the SRS may be a useful tool for identifying patients with TD with impairments in social communication that potentially place them at risk for bullying and other negative sequelae.
Published: 2017

8. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.

Author: Huang, Alden Y, Yu, Dongmei, Davis, Lea K, Sul, Jae Hoon, Tsetsos, Fotis, Ramensky, Vasily, Zelaya, Ivette, Ramos, Eliana Marisa, Osiecki, Lisa, Chen, Jason A, McGrath, Lauren M, Illmann, Cornelia, Sandor, Paul, Barr, Cathy L, Grados, Marco, Singer, Harvey S, Nöthen, Markus M, Hebebrand, Johannes, King, Robert A, Dion, Yves, Rouleau, Guy, Budman, Cathy L, Depienne, Christel, Worbe, Yulia, Hartmann, Andreas, Müller-Vahl, Kirsten R, Stuhrmann, Manfred, Aschauer, Harald, Stamenkovic, Mara, Schloegelhofer, Monika, Konstantinidis, Anastasios, Lyon, Gholson J, McMahon, William M, Barta, Csaba, Tarnok, Zsanett, Nagy, Peter, Batterson, James R, Rizzo, Renata, Cath, Danielle C, Wolanczyk, Tomasz, Berlin, Cheston, Malaty, Irene A, Okun, Michael S, Woods, Douglas W, Rees, Elliott, Pato, Carlos N, Pato, Michele T, Knowles, James A, Posthuma, Danielle, Pauls, David L, Cox, Nancy J, Neale, Benjamin M, Freimer, Nelson B, Paschou, Peristera, Mathews, Carol A, Scharf, Jeremiah M, Coppola, Giovanni, Tourette Syndrome Association International Consortium for Genetics (TSAICG), and Gilles de la Tourette Syndrome GWAS Replication Initiative (GGRI)
Subjects: Tourette Syndrome Association International Consortium for Genetics, Gilles de la Tourette Syndrome GWAS Replication Initiative, Humans, Tourette Syndrome, Genetic Predisposition to Disease, Calcium-Binding Proteins, Cell Adhesion Molecules, Neuronal, Neural Cell Adhesion Molecules, Nerve Tissue Proteins, Odds Ratio, Case-Control Studies, Genotype, Adolescent, Adult, Child, Female, Male, Genome-Wide Association Study, Young Adult, DNA Copy Number Variations, Contactins, White People, CNTN6, NRXN1, copy number variation, genetics, neurodevelopmental disorders, structural variation, tic disorders, Prevention, Human Genome, Genetics, Brain Disorders, Neurodegenerative, Neurosciences, Mental Health, 2.1 Biological and endogenous factors, Aetiology, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract: Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (< 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (> 1 Mb), singleton events (OR = 2.28, 95% CI [1.39-3.79], p = 1.2 × 10-3) and known, pathogenic CNVs (OR = 3.03 [1.85-5.07], p = 1.5 × 10-5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6-156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3-45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.
Published: 2017

9. Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

Author: Darrow, Sabrina M, Hirschtritt, Matthew E, Davis, Lea K, Illmann, Cornelia, Osiecki, Lisa, Grados, Marco, Sandor, Paul, Dion, Yves, King, Robert, Pauls, David, Budman, Cathy L, Cath, Danielle C, Greenberg, Erica, Lyon, Gholson J, Yu, Dongmei, McGrath, Lauren M, McMahon, William M, Lee, Paul C, Delucchi, Kevin L, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Syndrome Association International Consortium for Genetics
Subjects: Tourette Syndrome Association International Consortium for Genetics, Humans, Tourette Syndrome, Genetic Predisposition to Disease, Risk Assessment, Mothers, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity, Comorbidity, Multifactorial Inheritance, Phenotype, Adolescent, Adult, Middle Aged, Child, Child, Preschool, Child of Impaired Parents, Female, Male, Genome-Wide Association Study, Young Adult, Endophenotypes, Attention Deficit Hyperactivity Disorder, Genetics, Latent Variable Modeling, Tourette’s Disorder, Genetic Testing, Pediatric, Brain Disorders, Serious Mental Illness, Mental Health, Clinical Research, Anxiety Disorders, Human Genome, Attention Deficit Hyperactivity Disorder (ADHD), Neurodegenerative, Aetiology, 2.1 Biological and endogenous factors, Mental health, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectivePhenotypic heterogeneity in Tourette syndrome is partly due to complex genetic relationships among Tourette syndrome, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD). Identifying symptom-based endophenotypes across diagnoses may aid gene-finding efforts.MethodAssessments for Tourette syndrome, OCD, and ADHD symptoms were conducted in a discovery sample of 3,494 individuals recruited for genetic studies. Symptom-level factor and latent class analyses were conducted in Tourette syndrome families and replicated in an independent sample of 882 individuals. Classes were characterized by comorbidity rates and proportion of parents included. Heritability and polygenic load associated with Tourette syndrome, OCD, and ADHD were estimated.ResultsThe authors identified two cross-disorder symptom-based phenotypes across analyses: symmetry (symmetry, evening up, checking obsessions; ordering, arranging, counting, writing-rewriting compulsions, repetitive writing tics) and disinhibition (uttering syllables/words, echolalia/palilalia, coprolalia/copropraxia, and obsessive urges to offend/mutilate/be destructive). Heritability estimates for both endophenotypes were high and statistically significant (disinhibition factor=0.35, SE=0.03; symmetry factor=0.39, SE=0.03; symmetry class=0.38, SE=0.10). Mothers of Tourette syndrome probands had high rates of symmetry (49%) but not disinhibition (5%). Polygenic risk scores derived from a Tourette syndrome genome-wide association study (GWAS) were significantly associated with symmetry, while risk scores derived from an OCD GWAS were not. OCD polygenic risk scores were significantly associated with disinhibition, while Tourette syndrome and ADHD risk scores were not.ConclusionsThe analyses identified two heritable endophenotypes related to Tourette syndrome that cross traditional diagnostic boundaries. The symmetry phenotype correlated with Tourette syndrome polygenic load and was present in otherwise Tourette-unaffected mothers, suggesting that this phenotype may reflect additional Tourette syndrome (rather than OCD) genetic liability that is not captured by traditional DSM-based diagnoses.
Published: 2017

10. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

Author: Hirschtritt, Matthew E, Darrow, Sabrina M, Illmann, Cornelia, Osiecki, Lisa, Grados, Marco, Sandor, Paul, Dion, Yves, King, Robert A, Pauls, David L, Budman, Cathy L, Cath, Danielle C, Greenberg, Erica, Lyon, Gholson J, Yu, Dongmei, McGrath, Lauren M, McMahon, William M, Lee, Paul C, Delucchi, Kevin L, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Syndrome Association International Consortium for Genetics (TSAICG)
Subjects: Tourette Syndrome Association International Consortium for Genetics, Humans, Tourette Syndrome, Tics, Factor Analysis, Statistical, Social Behavior, Obsessive-Compulsive Disorder, Attention Deficit Disorder with Hyperactivity, Age of Onset, Comorbidity, Phenotype, Adolescent, Adult, Canada, United States, Netherlands, Female, Male, Young Adult, United Kingdom, Inhibition, Psychological, Brain Disorders, Neurodegenerative, Neurosciences, Genetics, Serious Mental Illness, Mental Health, Mental health, Clinical Sciences, Cognitive Sciences, Neurology & Neurosurgery
Abstract: ObjectiveTo identify heritable symptom-based subtypes of Tourette syndrome (TS).MethodsForty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.ResultsA 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 × 10(-18)).ConclusionsExpanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.
Published: 2016

11. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

Author: Hirschtritt, Matthew E, Lee, Paul C, Pauls, David L, Dion, Yves, Grados, Marco A, Illmann, Cornelia, King, Robert A, Sandor, Paul, McMahon, William M, Lyon, Gholson J, Cath, Danielle C, Kurlan, Roger, Robertson, Mary M, Osiecki, Lisa, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Syndrome Association International Consortium for Genetics
Subjects: Tourette Syndrome Association International Consortium for Genetics, Humans, Tourette Syndrome, Prevalence, Risk Factors, Mental Disorders, Age Factors, Age of Onset, Comorbidity, Age Distribution, Adolescent, Child, Child, Preschool, Canada, United States, Netherlands, Female, Male, Young Adult, United Kingdom, Brain Disorders, Neurodegenerative, Clinical Research, Anxiety Disorders, Behavioral and Social Science, Serious Mental Illness, Genetics, Attention Deficit Hyperactivity Disorder (ADHD), Pediatric, Neurosciences, Prevention, Mental Health, Aetiology, 2.3 Psychological, social and economic factors, Mental health, Other Medical and Health Sciences, Psychology, Cognitive Sciences
Abstract: ImportanceTourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (
Published: 2015

12. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

Author: Yu, Dongmei, Mathews, Carol A, Scharf, Jeremiah M, Neale, Benjamin M, Davis, Lea K, Gamazon, Eric R, Derks, Eske M, Evans, Patrick, Edlund, Christopher K, Crane, Jacquelyn, Fagerness, Jesen A, Osiecki, Lisa, Gallagher, Patience, Gerber, Gloria, Haddad, Stephen, Illmann, Cornelia, McGrath, Lauren M, Mayerfeld, Catherine, Arepalli, Sampath, Barlassina, Cristina, Barr, Cathy L, Bellodi, Laura, Benarroch, Fortu, Berrió, Gabriel Bedoya, Bienvenu, O Joseph, Black, Donald W, Bloch, Michael H, Brentani, Helena, Bruun, Ruth D, Budman, Cathy L, Camarena, Beatriz, Campbell, Desmond D, Cappi, Carolina, Silgado, Julio C Cardona, Cavallini, Maria C, Chavira, Denise A, Chouinard, Sylvain, Cook, Edwin H, Cookson, MR, Coric, Vladimir, Cullen, Bernadette, Cusi, Daniele, Delorme, Richard, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald L, Girard, Simon L, Grabe, Hans J, Grados, Marco A, Greenberg, Benjamin D, Gross-Tsur, Varda, Grünblatt, Edna, Hardy, John, Heiman, Gary A, Hemmings, Sian MJ, Herrera, Luis D, Hezel, Dianne M, Hoekstra, Pieter J, Jankovic, Joseph, Kennedy, James L, King, Robert A, Konkashbaev, Anuar I, Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F, Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L, Lupoli, Sara, Macciardi, Fabio, Maier, Wolfgang, Manunta, Paolo, Marconi, Maurizio, McCracken, James T, Mesa Restrepo, Sandra C, Moessner, Rainald, Moorjani, Priya, Morgan, Jubel, Muller, Heike, Murphy, Dennis L, Naarden, Allan L, Nurmi, Erika, Ochoa, William Cornejo, Ophoff, Roel A, Pakstis, Andrew J, Pato, Michele T, Pato, Carlos N, Piacentini, John, Pittenger, Christopher, and Pollak, Yehuda
Subjects: Humans, Tourette Syndrome, Severity of Illness Index, Obsessive-Compulsive Disorder, Psychiatric Status Rating Scales, Comorbidity, Polymorphism, Single Nucleotide, Adult, Female, Male, Genome-Wide Association Study, Human Genome, Genetics, Brain Disorders, Serious Mental Illness, Neurodegenerative, Prevention, Anxiety Disorders, Mental Health, Neurosciences, 2.1 Biological and endogenous factors, Aetiology, Mental health, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract: ObjectiveObsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.MethodThe authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.ResultsAlthough no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).ConclusionsPrevious work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
Published: 2015

13. 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 MJ, 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, and Oostra, Ben A
Subjects: Human Genome, Genetics, Brain Disorders, Serious Mental Illness, Neurodegenerative, Mental Health, Tourette Syndrome, Neurosciences, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Mental health, Adolescent, DNA Copy Number Variations, Diagnostic and Statistical Manual of Mental Disorders, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Obsessive-Compulsive Disorder, Polymorphism, Single Nucleotide, Tourette syndrome, obsessive-compulsive disorder, copy number variation, genetics, 16p13.11, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental & Child Psychology
Abstract: ObjectiveObsessive-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

14. Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

Author: Tsetsos, Fotis, primary, Topaloudi, Apostolia, additional, Jain, Pritesh, additional, Yang, Zhiyu, additional, Yu, Dongmei, additional, Kolovos, Petros, additional, Tumer, Zeynep, additional, Rizzo, Renata, additional, Hartmann, Andreas, additional, Depienne, Christel, additional, Worbe, Yulia, additional, Müller-Vahl, Kirsten R., additional, Cath, Danielle C., additional, Boomsma, Dorret I., additional, Wolanczyk, Tomasz, additional, Zekanowski, Cezary, additional, Barta, Csaba, additional, Nemoda, Zsofia, additional, Tarnok, Zsanett, additional, Padmanabhuni, Shanmukha S., additional, Buxbaum, Joseph D., additional, Grice, Dorothy, additional, Glennon, Jeffrey, additional, Stefansson, Hreinn, additional, Hengerer, Bastian, additional, Yannaki, Evangelia, additional, Stamatoyannopoulos, John A., additional, Benaroya-Milshtein, Noa, additional, Cardona, Francesco, additional, Hedderly, Tammy, additional, Heyman, Isobel, additional, Huyser, Chaim, additional, Mir, Pablo, additional, Morer, Astrid, additional, Mueller, Norbert, additional, Munchau, Alexander, additional, Plessen, Kerstin J., additional, Porcelli, Cesare, additional, Roessner, Veit, additional, Walitza, Susanne, additional, Schrag, Anette, additional, Martino, Davide, additional, Tischfield, Jay A., additional, Heiman, Gary A., additional, Willsey, A. Jeremy, additional, Dietrich, Andrea, additional, Davis, Lea K., additional, Crowley, James J., additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, Georgitsi, Marianthi, additional, Hoekstra, Pieter J., additional, Paschou, Peristera, additional, Barr, Cathy L., additional, Batterson, James R., additional, Berlin, Cheston, additional, Budman, Cathy L., additional, Coppola, Giovanni, additional, Cox, Nancy J., additional, Darrow, Sabrina, additional, Dion, Yves, additional, Freimer, Nelson B., additional, Grados, Marco A., additional, Greenberg, Erica, additional, Hirschtritt, Matthew E., additional, Huang, Alden Y., additional, Illmann, Cornelia, additional, King, Robert A., additional, Kurlan, Roger, additional, Leckman, James F., additional, Lyon, Gholson J., additional, Malaty, Irene A., additional, McMahon, William M., additional, Neale, Benjamin M., additional, Okun, Michael S., additional, Osiecki, Lisa, additional, Robertson, Mary M., additional, Rouleau, Guy A., additional, Sandor, Paul, additional, Singer, Harvey S., additional, Smit, Jan H., additional, Sul, Jae Hoon, additional, Androutsos, Christos, additional, Basha, Entela, additional, Farkas, Luca, additional, Fichna, Jakub, additional, Janik, Piotr, additional, Kapisyzi, Mira, additional, Karagiannidis, Iordanis, additional, Koumoula, Anastasia, additional, Nagy, Peter, additional, Puchala, Joanna, additional, Szejko, Natalia, additional, Szymanska, Urszula, additional, Tsironi, Vaia, additional, Apter, Alan, additional, Ball, Juliane, additional, Bodmer, Benjamin, additional, Bognar, Emese, additional, Buse, Judith, additional, Vela, Marta Correa, additional, Fremer, Carolin, additional, Garcia-Delgar, Blanca, additional, Gulisano, Mariangela, additional, Hagen, Annelieke, additional, Hagstrøm, Julie, additional, Madruga-Garrido, Marcos, additional, Pellico, Alessandra, additional, Ruhrman, Daphna, additional, Schnell, Jaana, additional, Silvestri, Paola Rosaria, additional, Skov, Liselotte, additional, Steinberg, Tamar, additional, Gloor, Friederike Tagwerker, additional, Turner, Victoria L., additional, Weidinger, Elif, additional, Alexander, John, additional, Aranyi, Tamas, additional, Buisman, Wim R., additional, Buitelaar, Jan K., additional, Driessen, Nicole, additional, Drineas, Petros, additional, Fan, Siyan, additional, Forde, Natalie J., additional, Gerasch, Sarah, additional, van den Heuvel, Odile A., additional, Jespersgaard, Cathrine, additional, Kanaan, Ahmad S., additional, Möller, Harald E., additional, Nawaz, Muhammad S., additional, Nespoli, Ester, additional, Pagliaroli, Luca, additional, Poelmans, Geert, additional, Pouwels, Petra J.W., additional, Rizzo, Francesca, additional, Veltman, Dick J., additional, van der Werf, Ysbrand D., additional, Widomska, Joanna, additional, Zilhäo, Nuno R., additional, Brown, Lawrence W., additional, Cheon, Keun-Ah, additional, Coffey, Barbara J., additional, Fernandez, Thomas V., additional, Gilbert, Donald L., additional, Hong, Hyun Ju, additional, Ibanez-Gomez, Laura, additional, Kim, Eun-Joo, additional, Kim, Young Key, additional, Kim, Young-Shin, additional, Koh, Yun-Joo, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L., additional, Maras, Athanasios, additional, Murphy, Tara L., additional, Shin, Eun-Young, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, State, Matthew W., additional, Visscher, Frank, additional, Wang, Sheng, additional, and Zinner, Samuel H., additional
Published: 2023
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15. Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses

Author: Darrow, Sabrina M., Illmann, Cornelia, Gauvin, Caitlin, Osiecki, Lisa, Egan, Crystelle A., Greenberg, Erica, Eckfield, Monika, Hirschtritt, Matthew E., Pauls, David L., Batterson, James R., Berlin, Cheston M., Malaty, Irene A., Woods, Douglas W., Scharf, Jeremiah M., and Mathews, Carol A.
Published: 2015
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16. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

Author: Claudio-Campos, Karla, Stevens, Daniel, Koo, Sang-Wahn, Valko, Alexa, Bienvenu, Oscar Joseph, Budman, Cathy B, Cath, Danielle C, Darrow, Sabrina, Geller, Daniel, Goes, Fernando S, Grados, Marco A, Greenberg, Benjamin D, Greenberg, Erica, Hirschtritt, Matthew E, Illmann, Cornelia, Ivankovic, Franjo, King, Robert A, Knowles, James A, Krasnow, Janice, Lee, Paul C, Lyon, Gholson J, McCracken, James T, Robertson, Mary M, Osiecki, Lisa, Riddle, Mark A, Rouleau, Guy, Sandor, Paul, Nestadt, Gerald, Samuels, Jack, Scharf, Jeremiah M, Mathews, Carol A, and Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study (OCGAS)
Subjects: Obsessive-Compulsive Disorder, analysis, Clinical Sciences, severity, Comorbidity, Neurodegenerative, Tourette Association of America International Consortium for Genetics (TAAICG) and the OCD Collaborative Genetics Association Study, chronic tics, Behavioral and Social Science, Humans, 2.1 Biological and endogenous factors, Aetiology, Neurology & Neurosurgery, Tourette, Neurosciences, meta&#8208, Human Movement and Sports Sciences, Serious Mental Illness, Anxiety Disorders, Brain Disorders, meta-analysis, Mental Health, Attention Deficit Disorder with Hyperactivity, Tic Disorders, Tics, Tourette Syndrome
Abstract: BackgroundPersistent motor or vocal tic disorder (PMVT) has been hypothesized to be a forme fruste of Tourette syndrome (TS). Although the primary diagnostic criterion for PMVT (presence of motor or vocal tics, but not both) is clear, less is known about its clinical presentation.ObjectiveThe goals of this study were to compare the prevalence and number of comorbid psychiatric disorders, tic severity, age at tic onset, and family history for TS and PMVT.MethodsWe analyzed data from two independent cohorts using generalized linear equations and confirmed our findings using meta-analyses, incorporating data from previously published literature.ResultsRates of obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) were lower in PMVT than in TS in all analyses. Other psychiatric comorbidities occurred with similar frequencies in PMVT and TS in both cohorts, although meta-analyses suggested lower rates of most psychiatric disorders in PMVT compared with TS. ADHD and OCD increased the odds of comorbid mood, anxiety, substance use, and disruptive behaviors, and accounted for observed differences between PMVT and TS. Age of tic onset was approximately 2 years later, and tic severity was lower in PMVT than in TS. First-degree relatives had elevated rates of TS, PMVT, OCD, and ADHD compared with population prevalences, with rates of TS equal to or greater than PMVT rates.ConclusionsOur findings support the hypothesis that PMVT and TS occur along a clinical spectrum in which TS is a more severe and PMVT a less severe manifestation of a continuous neurodevelopmental tic spectrum disorder. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Published: 2021

17. Synaptic processes and immune-related pathways implicated in Tourette Syndrome

Author: Tsetsos, Fotis, primary, Yu, Dongmei, additional, Sul, Jae Hoon, additional, Huang, Alden Y., additional, Illmann, Cornelia, additional, Osiecki, Lisa, additional, Darrow, Sabrina M., additional, Hirschtritt, Matthew E., additional, Greenberg, Erica, additional, Muller-Vahl, Kirsten R., additional, Stuhrmann, Manfred, additional, Dion, Yves, additional, Rouleau, Guy A., additional, Aschauer, Harald, additional, Stamenkovic, Mara, additional, Schlögelhofer, Monika, additional, Sandor, Paul, additional, Barr, Cathy L., additional, Grados, Marco A., additional, Singer, Harvey S., additional, Nöthen, Markus M., additional, Hebebrand, Johannes, additional, Hinney, Anke, additional, King, Robert A., additional, Fernandez, Thomas V., additional, Barta, Csaba, additional, Tarnok, Zsanett, additional, Nagy, Peter, additional, Depienne, Christel, additional, Worbe, Yulia, additional, Hartmann, Andreas, additional, Budman, Cathy L., additional, Rizzo, Renata, additional, Lyon, Gholson J., additional, McMahon, William M., additional, Batterson, James R., additional, Cath, Danielle C., additional, Malaty, Irene A., additional, Okun, Michael S., additional, Berlin, Cheston, additional, Woods, Douglas W., additional, Lee, Paul C., additional, Jankovic, Joseph, additional, Robertson, Mary M., additional, Gilbert, Donald L., additional, Brown, Lawrence W., additional, Coffey, Barbara J., additional, Dietrich, Andrea, additional, Hoekstra, Pieter J., additional, Kuperman, Samuel, additional, Zinner, Samuel H., additional, Wagner, Michael, additional, Knowles, James A, additional, Willsey, A. Jeremy, additional, Tischfield, Jay A., additional, Heiman, Gary A., additional, Cox, Nancy J., additional, Freimer, Nelson B., additional, Neale, Benjamin M., additional, Davis, Lea K., additional, Coppola, Giovanni, additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, and Paschou, Peristera, additional
Published: 2020
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18. Analysis of shared heritability in common disorders of the brain

Author: Brainstorm Consortium, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K, Walters, Raymond K, Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J, Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A, Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H, Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-François, Duron, Emmanuelle, Vardarajan, Badri N, Reitz, Christiane, Goate, Alison M, Huentelman, Matthew J, Kamboh, M Ilyas, Larson, Eric B, Rogaeva, Ekaterina, St George-Hyslop, Peter, Hakonarson, Hakon, Kukull, Walter A, Farrer, Lindsay A, Barnes, Lisa L, Beach, Thomas G, Demirci, F Yesim, Head, Elizabeth, Hulette, Christine M, Jicha, Gregory A, Kauwe, John SK, Kaye, Jeffrey A, Leverenz, James B, Levey, Allan I, Lieberman, Andrew P, Pankratz, Vernon S, Poon, Wayne W, Quinn, Joseph F, Saykin, Andrew J, Schneider, Lon S, Smith, Amanda G, Sonnen, Joshua A, Stern, Robert A, Van Deerlin, Vivianna M, Van Eldik, Linda J, Harold, Denise, Russo, Giancarlo, Rubinsztein, David C, Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C, Hampel, Harald, Owen, Michael J, Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M, Rossor, Martin, Lupton, Michelle K, Hoffmann, Per, Kornhuber, Johannes, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C, Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J, De Jager, Philip L, Geschwind, Daniel H, Riemenschneider, Matthias, Riedel-Heller, Steffi, Rotter, Jerome I, Ransmayr, Gerhard, Hyman, Bradley T, Cruchaga, Carlos, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nicholas, Kurth, Tobias, Ligthart, Lannie, Terwindt, Gisela M, Freilinger, Tobias, Ran, Caroline, Gordon, Scott D, Borck, Guntram, Adams, Hieab HH, Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E, Schürks, Markus, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfons, Pozo-Rosich, Patricia, Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Metspalu, Andres, Kubisch, Christian, Ferrari, Michel D, Belin, Andrea C, Van Den Maagdenberg, Arn MJM, Zwart, John-Anker, Boomsma, Dorret, Eriksson, Nicholas, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Avbersek, Andreja, Baum, Larry, Berkovic, Samuel, Bradfield, Jonathan, Buono, Russell J, Catarino, Claudia B, Cossette, Patrick, De Jonghe, Peter, Depondt, Chantal, Dlugos, Dennis, Ferraro, Thomas N, French, Jacqueline, Hjalgrim, Helle, Jamnadas-Khoda, Jennifer, Kälviäinen, Reetta, Kunz, Wolfram S, Lerche, Holger, Leu, Costin, Lindhout, Dick, Lo, Warren, Lowenstein, Daniel, McCormack, Mark, Møller, Rikke S, Molloy, Anne, Ng, Ping-Wing, Oliver, Karen, Privitera, Michael, Radtke, Rodney, Ruppert, Ann-Kathrin, Sander, Thomas, Schachter, Steven, Schankin, Christoph, Scheffer, Ingrid, Schoch, Susanne, Sisodiya, Sanjay M, Smith, Philip, Sperling, Michael, Striano, Pasquale, Surges, Rainer, Thomas, G Neil, Visscher, Frank, Whelan, Christopher D, Zara, Federico, Heinzen, Erin L, Marson, Anthony, Becker, Felicitas, Stroink, Hans, Zimprich, Fritz, Gasser, Thomas, Gibbs, Raphael, Heutink, Peter, Martinez, Maria, Morris, Huw R, Sharma, Manu, Ryten, Mina, Mok, Kin Y, Pulit, Sara, Bevan, Steve, Holliday, Elizabeth, Attia, John, Battey, Thomas, Boncoraglio, Giorgio, Thijs, Vincent, Chen, Wei-Min, Mitchell, Braxton, Rothwell, Peter, Sharma, Pankaj, Sudlow, Cathie, Vicente, Astrid, Markus, Hugh, Kourkoulis, Christina, Pera, Joana, Raffeld, Miriam, Silliman, Scott, Boraska Perica, Vesna, Thornton, Laura M, Huckins, Laura M, William Rayner, N, Lewis, Cathryn M, Gratacos, Monica, Rybakowski, Filip, Keski-Rahkonen, Anna, Raevuori, Anu, Hudson, James I, Reichborn-Kjennerud, Ted, Monteleone, Palmiero, Karwautz, Andreas, Mannik, Katrin, Baker, Jessica H, O'Toole, Julie K, Trace, Sara E, Davis, Oliver SP, Helder, Sietske G, Ehrlich, Stefan, Herpertz-Dahlmann, Beate, Danner, Unna N, Van Elburg, Annemarie A, Clementi, Maurizio, Forzan, Monica, Docampo, Elisa, Lissowska, Jolanta, Hauser, Joanna, Tortorella, Alfonso, Maj, Mario, Gonidakis, Fragiskos, Tziouvas, Konstantinos, Papezova, Hana, Yilmaz, Zeynep, Wagner, Gudrun, Cohen-Woods, Sarah, Herms, Stefan, Julià, Antonio, Rabionet, Raquel, Dick, Danielle M, Ripatti, Samuli, Andreassen, Ole A, Espeseth, Thomas, Lundervold, Astri J, Steen, Vidar M, Pinto, Dalila, Scherer, Stephen W, Aschauer, Harald, Schosser, Alexandra, Alfredsson, Lars, Padyukov, Leonid, Halmi, Katherine A, Mitchell, James, Strober, Michael, Bergen, Andrew W, Kaye, Walter, Szatkiewicz, Jin Peng, Cormand, Bru, Ramos-Quiroga, Josep Antoni, Sánchez-Mora, Cristina, Ribasés, Marta, Casas, Miguel, Hervas, Amaia, Arranz, Maria Jesús, Haavik, Jan, Zayats, Tetyana, Johansson, Stefan, Williams, Nigel, Dempfle, Astrid, Rothenberger, Aribert, Kuntsi, Jonna, Oades, Robert D, Banaschewski, Tobias, Franke, Barbara, Buitelaar, Jan K, Arias Vasquez, Alejandro, Doyle, Alysa E, Reif, Andreas, Lesch, Klaus-Peter, Freitag, Christine, Rivero, Olga, Palmason, Haukur, Romanos, Marcel, Langley, Kate, Rietschel, Marcella, Witt, Stephanie H, Dalsgaard, Soeren, Børglum, Anders D, Waldman, Irwin, Wilmot, Beth, Molly, Nikolas, Bau, Claiton HD, Crosbie, Jennifer, Schachar, Russell, Loo, Sandra K, McGough, James J, Grevet, Eugenio H, Medland, Sarah E, Robinson, Elise, Weiss, Lauren A, Bacchelli, Elena, Bailey, Anthony, Bal, Vanessa, Battaglia, Agatino, Betancur, Catalina, Bolton, Patrick, Cantor, Rita, Celestino-Soper, Patrícia, Dawson, Geraldine, De Rubeis, Silvia, Duque, Frederico, Green, Andrew, Klauck, Sabine M, Leboyer, Marion, Levitt, Pat, Maestrini, Elena, Mane, Shrikant, De-Luca, Daniel Moreno, Parr, Jeremy, Regan, Regina, Reichenberg, Abraham, Sandin, Sven, Vorstman, Jacob, Wassink, Thomas, Wijsman, Ellen, Cook, Edwin, Santangelo, Susan, Delorme, Richard, Rogé, Bernadette, Magalhaes, Tiago, Arking, Dan, Schulze, Thomas G, Thompson, Robert C, Strohmaier, Jana, Matthews, Keith, Melle, Ingrid, Morris, Derek, Blackwood, Douglas, McIntosh, Andrew, Bergen, Sarah E, Schalling, Martin, Jamain, Stéphane, Maaser, Anna, Fischer, Sascha B, Reinbold, Céline S, Fullerton, Janice M, Guzman-Parra, José, Mayoral, Fermin, Schofield, Peter R, Cichon, Sven, Mühleisen, Thomas W, Degenhardt, Franziska, Schumacher, Johannes, Bauer, Michael, Mitchell, Philip B, Gershon, Elliot S, Rice, John, Potash, James B, Zandi, Peter P, Craddock, Nick, Ferrier, I Nicol, Alda, Martin, Rouleau, Guy A, Turecki, Gustavo, Ophoff, Roel, Pato, Carlos, Anjorin, Adebayo, Stahl, Eli, Leber, Markus, Czerski, Piotr M, Cruceanu, Cristiana, Jones, Ian R, Posthuma, Danielle, Andlauer, Till FM, Forstner, Andreas J, Streit, Fabian, Baune, Bernhard T, Air, Tracy, Sinnamon, Grant, Wray, Naomi R, MacIntyre, Donald J, Porteous, David, Homuth, Georg, Rivera, Margarita, Grove, Jakob, Middeldorp, Christel M, Hickie, Ian, Pergadia, Michele, Mehta, Divya, Smit, Johannes H, Jansen, Rick, De Geus, Eco, Dunn, Erin, Li, Qingqin S, Nauck, Matthias, Schoevers, Robert A, Beekman, Aartjan Tf, Knowles, James A, Viktorin, Alexander, Arnold, Paul, Barr, Cathy L, Bedoya-Berrio, Gabriel, Bienvenu, O Joseph, Brentani, Helena, Burton, Christie, Camarena, Beatriz, Cappi, Carolina, Cath, Danielle, Cavallini, Maria, Cusi, Daniele, Darrow, Sabrina, Denys, Damiaan, Derks, Eske M, Dietrich, Andrea, Fernandez, Thomas, Figee, Martijn, Freimer, Nelson, Gerber, Gloria, Grados, Marco, Greenberg, Erica, Hanna, Gregory L, Hartmann, Andreas, Hirschtritt, Matthew E, Hoekstra, Pieter J, Huang, Alden, Huyser, Chaim, Illmann, Cornelia, Jenike, Michael, Kuperman, Samuel, Leventhal, Bennett, Lochner, Christine, Lyon, Gholson J, Macciardi, Fabio, Madruga-Garrido, Marcos, Malaty, Irene A, Maras, Athanasios, McGrath, Lauren, Miguel, Eurípedes C, Mir, Pablo, Nestadt, Gerald, Nicolini, Humberto, Okun, Michael S, Pakstis, Andrew, Paschou, Peristera, Piacentini, John, Pittenger, Christopher, Plessen, Kerstin, Ramensky, Vasily, Ramos, Eliana M, Reus, Victor, Richter, Margaret A, Riddle, Mark A, Robertson, Mary M, Roessner, Veit, Rosário, Maria, Samuels, Jack F, Sandor, Paul, Stein, Dan J, Tsetsos, Fotis, Van Nieuwerburgh, Filip, Weatherall, Sarah, Wendland, Jens R, Wolanczyk, Tomasz, Worbe, Yulia, Zai, Gwyneth, Goes, Fernando S, McLaughlin, Nicole, Nestadt, Paul S, Grabe, Hans-Jorgen, Depienne, Christel, Konkashbaev, Anuar, Lanzagorta, Nuria, Valencia-Duarte, Ana, Bramon, Elvira, Buccola, Nancy, Cahn, Wiepke, Cairns, Murray, Chong, Siow A, Cohen, David, Crespo-Facorro, Benedicto, Crowley, James, Davidson, Michael, DeLisi, Lynn, Dinan, Timothy, Donohoe, Gary, Drapeau, Elodie, Duan, Jubao, Haan, Lieuwe, Hougaard, David, Karachanak-Yankova, Sena, Khrunin, Andrey, Klovins, Janis, Kučinskas, Vaidutis, Lee Chee Keong, Jimmy, Limborska, Svetlana, Loughland, Carmel, Lönnqvist, Jouko, Maher, Brion, Mattheisen, Manuel, McDonald, Colm, Murphy, Kieran C, Nenadic, Igor, Van Os, Jim, Pantelis, Christos, Pato, Michele, Petryshen, Tracey, Quested, Digby, Roussos, Panos, Sanders, Alan R, Schall, Ulrich, Schwab, Sibylle G, Sim, Kang, So, Hon-Cheong, Stögmann, Elisabeth, Subramaniam, Mythily, Toncheva, Draga, Waddington, John, Walters, James, Weiser, Mark, Cheng, Wei, Cloninger, Robert, Curtis, David, Gejman, Pablo V, Henskens, Frans, Mattingsdal, Morten, Oh, Sang-Yun, Scott, Rodney, Webb, Bradley, Breen, Gerome, Churchhouse, Claire, Bulik, Cynthia M, Daly, Mark, Dichgans, Martin, Faraone, Stephen V, Guerreiro, Rita, Holmans, Peter, Kendler, Kenneth S, Koeleman, Bobby, Mathews, Carol A, Price, Alkes, Scharf, Jeremiah, Sklar, Pamela, Williams, Julie, Wood, Nicholas W, Cotsapas, Chris, Palotie, Aarno, Smoller, Jordan W, Sullivan, Patrick, Rosand, Jonathan, Corvin, Aiden, Neale, Benjamin M, Schott, Jonathan M, Anney, Richard, Elia, Josephine, Grigoroiu-Serbanescu, Maria, Edenberg, Howard J, Murray, Robin, Massachusetts General Hospital [Boston], Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), School of Psychology [Cardiff University], Cardiff University, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), New Jersey Institute of Technology [Newark] (NJIT), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neurologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gériatrie générale et aigüe [Paris], AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Columbia University [New York], Dpt of Neuroscience [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Washington [Seattle], Tanz Center Research in Neurodegenerative Diseases [Toronto], University of Toronto, Children’s Hospital of Philadelphia (CHOP ), University of Kentucky (UK), School of medicine, Duke University [Durham], College of medicine, Brigham Young University (BYU), Oregon Health and Science University [Portland] (OHSU), Cleveland Clinic, Department of Neurology, Emory University [Atlanta, GA], Medical School, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Health sciences center, The University of New Mexico [Albuquerque], Institute for Memory Impairments and Neurological Disorders [Irvine], University of California [Irvine] (UC Irvine), University of California (UC)-University of California (UC), Indiana University - Purdue University Indianapolis (IUPUI), Indiana University System, Keck School of Medicine [Los Angeles], University of Southern California (USC), University of South Florida [Tampa] (USF), University of Utah School of Medicine [Salt Lake City], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Perelman School of Medicine, University of Pennsylvania, Dublin City University [Dublin] (DCU), Functional Genomics Center Zurich, Universität Zürich [Zürich] = University of Zurich (UZH)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Aristotle University of Thessaloniki, Maurice Wohl Clinical Neuroscience Institut, King‘s College London, Dementia Research Centre [London] (DRC), Groupe de recherche clinique Alzheimer Precision Medicine (GRC 21 - APM), Sorbonne Université (SU), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, MRC Prion Unit [London], Queen's University [Belfast] (QUB), School of Life Sciences, University of Nottingham, UK (UON), Rheinische Friedrich-Wilhelms-Universität Bonn, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), School of Medicine [Dublin], Trinity College Dublin, Department of Medicine, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), School of Public Health [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Columbia University Medical Center (CUMC), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Saarland University [Saarbrücken], Universität Leipzig, School of Medicine [Los Angeles], Johannes Kepler Universität Linz - Johannes Kepler University Linz [Autriche] (JKU), Department of Neurology [Boston], Harvard Medical School [Boston] (HMS)-Massachusetts General Hospital [Boston], School of Medecine, Washington University in Saint Louis (WUSTL), Oslo University Hospital [Oslo], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, 23andMe Inc., Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Biological Psychology [Amsterdam], Vrije Universiteit Amsterdam [Amsterdam] (VU), Leiden University Medical Center (LUMC), Universiteit Leiden, University-Hospital Munich-Großhadern [München], Karolinska Institutet [Stockholm], Universität Ulm - Ulm University [Ulm, Allemagne], Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), Landspitali National University Hospital of Iceland, VU University Medical Center [Amsterdam], Boston VA Research Institute (BVARI), Department of Physiology, Anatomy and Genetics [Oxford], University of Oxford, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Christian-Albrechts-Universität zu Kiel (CAU), Institute of Clinical Molecular Biology, Kiel University, National Institute for Health and Welfare [Helsinki], Harvard T.H. Chan School of Public Health, Universitat Autònoma de Barcelona (UAB), Vall d'Hebron University Hospital [Barcelona], University of Tartu, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Center for Human and Clinical Genetics, Universiteit Leiden-Universiteit Leiden, University of Copenhagen = Københavns Universitet (UCPH), Institute of Health and Biomedical Innovation (IHBI), Queensland University of Technology [Brisbane] (QUT), Discipline of Psychiatry [Dublin], Trinity College Dublin-Trinity College Dublin, Institute of Neurology [London], The University of Hong Kong (HKU), University of Melbourne, Cooper Medical School of Rowan University [Camden] (CMSRU), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM), University of Antwerp (UA), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), New York University School of Medicine (NYU), New York University School of Medicine, NYU System (NYU)-NYU System (NYU), University of Eastern Finland, Universitätsklinikum Bonn (UKB), Hertie Institute for Clinical Brain Research [Tubingen], University of Tübingen, NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University Medical Center [Utrecht], Ohio State University [Columbus] (OSU), University of California [San Francisco] (UC San Francisco), University of California (UC), Royal College of Surgeons in Ireland (RCSI), University of Southern Denmark (SDU), United Christian Hospital [Hong Kong] (UCH), University of Cincinnati (UC), University of Cologne, Inselspital Bern, University of Wales, Jefferson University Hospitals, University of Liverpool, Medizinische Universität Wien = Medical University of Vienna, National Institutes of Health [Bethesda] (NIH), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Lincoln, University of Newcastle [Callaghan, Australia] (UoN), Fondazione IRCCS Istituto Neurologico 'Carlo Besta', University of Virginia, University of Maryland [Baltimore County] (UMBC), University of Maryland System, Royal Holloway [University of London] (RHUL), University of Edinburgh, Universidade de Lisboa = University of Lisbon (ULISBOA), Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), University of Split, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), McLean Hospital [Belmont, Ma.], Norwegian Institute of Public Health [Oslo] (NIPH), Università degli Studi di Salerno = University of Salerno (UNISA), University of Bristol [Bristol], Technische Universität Dresden = Dresden University of Technology (TU Dresden), Rheinisch-Westfälische Technische Hochschule Aachen University (RWTH), Utrecht University [Utrecht], Azienda Ospedaliera di Padova, Université de Liège, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology (MCMCC), Università degli Studi di Perugia = University of Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli' = University of the Study of Campania Luigi Vanvitelli, National and Kapodistrian University of Athens (NKUA), Charles University [Prague] (CU), SURFACES, Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Flinders University [Adelaide, Australia], Virginia Commonwealth University (VCU), University of Oslo (UiO), University of Bergen (UiB), Weill Medical College of Cornell University [New York], University of North Dakota [Grand Forks] (UND), Oregon Research Institute (ORI), University of California [San Diego] (UC San Diego), Universitat de Barcelona (UB), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), Hospital Universitario Mutua de Terrassa, School of Computer Science and Communication [Stockholm], Royal Institute of Technology [Stockholm] (KTH ), Jefferson (Philadelphia University + Thomas Jefferson University), University Medical Center Göttingen (UMG), Universität Heidelberg [Heidelberg] = Heidelberg University, Radboud University Medical Center [Nijmegen], Universitätsklinikum Frankfurt, Maastricht University [Maastricht], Institute of Psychological Medicine and Clinical Neurosciences, Aarhus University [Aarhus], University of Iowa [Iowa City], Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS), The Hospital for sick children [Toronto] (SickKids), Hospital de Clínicas de Porto Alegre (HCPA), Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), University of British Columbia (UBC), IRCCS Fondazione Stella Maris [Pisa], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Neuroscience Paris Seine (NPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de Coimbra [Coimbra], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Our Lady's Children's Hospital Crumlin (OLCHC), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Children’s Hospital Los Angeles [Los Angeles], Yale University [New Haven], Brown University, Institute of Neuroscience [Newcastle] (ION), Newcastle University [Newcastle], Department of Medical Epidemiology and Biostatistics (MEB), Division of Medical Genetics [Seattle], University of Illinois [Chicago] (UIC), University of Illinois System, Maine Medical Center Research Institute (MMCRI), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre d’Etudes et de Recherches en Psychopathologie et Psychologie de la Santé (CERPPS), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Toulouse Mind & Brain Institut (TMBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Johns Hopkins University School of Medicine [Baltimore], Ludwig Maximilian University [Munich] (LMU), University of Michigan System, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg] = Heidelberg University-Central Institute of Mental Health Mannheim, University of Dundee, National University of Ireland [Galway] (NUI Galway), University Hospital Basel [Basel], Neuroscience Research Australia (NeuRA), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW), University of Chicago, Johns Hopkins University (JHU), Johns Hopkins Bloomberg School of Public Health [Baltimore], Dalhousie University [Halifax], Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada], State University of New York (SUNY), University Hospital of Cologne [Cologne], University of Adelaide, James Cook University (JCU), Institute for Molecular Bioscience, University of Queensland [Brisbane], Greifswald University Hospital, The University of Sydney, University Medical Center Groningen [Groningen] (UMCG), University of Calgary, University Health Network, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Universidade de São Paulo = University of São Paulo (USP), Ospedale San Raffaele, University of Amsterdam [Amsterdam] (UvA), University of Groningen [Groningen], Yale School of Medicine [New Haven, Connecticut] (YSM), Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Cape Town, Cold Spring Harbor Laboratory (CSHL), Universidad de Sevilla / University of Sevilla, University of Florida [Gainesville] (UF), University of Denver, Purdue University [West Lafayette], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Moscow Institute of Physics and Technology [Moscow] (MIPT), Sunnybrook Health Sciences Centre, Federal Institute of São Paulo (IFSP), Democritus University of Thrace (DUTH), Universiteit Gent = Ghent University (UGENT), Medical University of Warsaw - Poland, Sorbonne Université - Faculté de Médecine - Département d'Enseignement et de Recherche en Médecine Générale, Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Institute of Mental Health [Singapore], Universidad de Cantabria [Santander], Tel Aviv University (TAU), University College Cork (UCC), University of Rochester [USA], Statens Serum Institut [Copenhagen], Софийски университет = Sofia University, Russian Academy of Sciences [Moscow] (RAS), Latvian Biomedical Research and Study Centre [Rīga], Vilnius University [Vilnius], Nanyang Technological University [Singapour], Department of Life Sciences, Imperial College London, Jena University Hospital [Jena], Oxford University Hospitals NHS Trust, Schizophrenia Research Institute [Sydney], Faculty of Science, Medicine and Health [Wollongong], University of Wollongong [Australia], City University of Hong Kong [Hong Kong] (CUHK), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), This work was supported by grants 1R01MH10764901 and 5U01MH09443203 from the National Institute of Mental Health, as well as the Orion Farmos Research Foundation (V.A.) and the Fannie and John Hertz Foundation (H.K.F.). Consortium specific funding is detailed in the supplementary materials ('Study-specific acknowledgments')., Brainstorm Consortium, University of Kentucky, University of California [Irvine] (UCI), University of California-University of California, University of Pennsylvania [Philadelphia], Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 AMP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Universität Leipzig [Leipzig], Johannes Kepler University Linz [Linz] (JKU), University of Helsinki-University of Helsinki, University of Helsinki, University of Oxford [Oxford], University of Copenhagen = Københavns Universitet (KU), University of California [San Francisco] (UCSF), University of California, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Newcastle [Australia] (UoN), University of Virginia [Charlottesville], Universidade de Lisboa (ULISBOA), Università degli Studi di Salerno (UNISA), Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Università degli Studi di Perugia (UNIPG), Università degli studi della Campania 'Luigi Vanvitelli', Universität Heidelberg [Heidelberg], Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, VU University Amsterdam, Universidade de São Paulo (USP), Yale University School of Medicine, Universidad de Sevilla, Universiteit Gent = Ghent University [Belgium] (UGENT), Service de Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière] (SPEA), Tel Aviv University [Tel Aviv], University of Sofia, Anttila, Verneri, Bulik-Sullivan, Brendan, Finucane, Hilary K., Walters, Raymond K., Bras, Jose, Duncan, Laramie, Escott-Price, Valentina, Falcone, Guido J., Gormley, Padhraig, Malik, Rainer, Patsopoulos, Nikolaos A., Ripke, Stephan, Wei, Zhi, Yu, Dongmei, Lee, Phil H., Turley, Patrick, Grenier-Boley, Benjamin, Chouraki, Vincent, Kamatani, Yoichiro, Berr, Claudine, Letenneur, Luc, Hannequin, Didier, Amouyel, Philippe, Boland, Anne, Deleuze, Jean-Françoi, Duron, Emmanuelle, Vardarajan, Badri N., Reitz, Christiane, Goate, Alison M., Huentelman, Matthew J., Ilyas Kamboh, M., Larson, Eric B., Rogaeva, Ekaterina, George-Hyslop, Peter St, Hakonarson, Hakon, Kukull, Walter A., Farrer, Lindsay A., Barnes, Lisa L., Beach, Thomas G., Yesim Demirci, F., Head, Elizabeth, Hulette, Christine M., Jicha, Gregory A., Kauwe, John S.K., Kaye, Jeffrey A., Leverenz, James B., Levey, Allan I., Lieberman, Andrew P., Pankratz, Vernon S., Poon, Wayne W., Quinn, Joseph F., Saykin, Andrew J., Schneider, Lon S., Smith, Amanda G., Sonnen, Joshua A., Stern, Robert A., Van Deerlin, Vivianna M., Van Eldik, Linda J., Harold, Denise, Russo, Giancarlo, Rubinsztein, David C., Bayer, Anthony, Tsolaki, Magda, Proitsi, Petra, Fox, Nick C., Hampel, Harald, Owen, Michael J., Mead, Simon, Passmore, Peter, Morgan, Kevin, Nöthen, Markus M., Rossor, Martin, Lupton, Michelle K., Hoffmann, Per, Kornhuber, Johanne, Lawlor, Brian, McQuillin, Andrew, Al-Chalabi, Ammar, Bis, Joshua C., Ruiz, Agustin, Boada, Mercè, Seshadri, Sudha, Beiser, Alexa, Rice, Kenneth, Van Der Lee, Sven J., De Jager, Philip L., Geschwind, Daniel H., Riemenschneider, Matthia, Riedel-Heller, Steffi, Rotter, Jerome I., Ransmayr, Gerhard, Hyman, Bradley T., Cruchaga, Carlo, Alegret, Montserrat, Winsvold, Bendik, Palta, Priit, Farh, Kai-How, Cuenca-Leon, Ester, Furlotte, Nichola, Kurth, Tobia, Ligthart, Lannie, Terwindt, Gisela M., Freilinger, Tobia, Ran, Caroline, Gordon, Scott D., Borck, Guntram, Adams, Hieab H.H., Lehtimäki, Terho, Wedenoja, Juho, Buring, Julie E., Schürks, Marku, Hrafnsdottir, Maria, Hottenga, Jouke-Jan, Penninx, Brenda, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Martin, Nicholas G., Montgomery, Grant W., Kurki, Mitja I., Hämäläinen, Eija, Huang, Hailiang, Huang, Jie, Sandor, Cynthia, Webber, Caleb, Muller-Myhsok, Bertram, Schreiber, Stefan, Salomaa, Veikko, Loehrer, Elizabeth, Göbel, Hartmut, Macaya, Alfon, Pozo-Rosich, Patricia, Hansen, Thoma, Werge, Thoma, Kaprio, Jaakko, Metspalu, Andre, Kubisch, Christian, Ferrari, Michel D., Belin, Andrea C., Van Den Maagdenberg, Arn M. 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Duque, F, Green, A, Klauck, S, Leboyer, M, Levitt, P, Maestrini, E, Mane, S, Moreno-De-Luca, D, Parr, J, Regan, R, Reichenberg, A, Sandin, S, Vorstman, J, Wassink, T, Wijsman, E, Cook, E, Santangelo, S, Delorme, R, Roge, B, Magalhaes, T, Arking, D, Schulze, T, Thompson, R, Strohmaier, J, Matthews, K, Melle, I, Morris, D, Blackwood, D, Mcintosh, A, Bergen, S, Schalling, M, Jamain, S, Maaser, A, Fischer, S, Reinbold, C, Fullerton, J, Guzman-Parra, J, Mayoral, F, Schofield, P, Cichon, S, Mühleisen, T, Degenhardt, F, Schumacher, J, Bauer, M, Mitchell, P, Gershon, E, Rice, J, Potash, J, Zandi, P, Craddock, N, Nicol Ferrier, I, Alda, M, Rouleau, G, Turecki, G, Ophoff, R, Pato, C, Anjorin, A, Stahl, E, Leber, M, Czerski, P, Cruceanu, C, Jones, I, Posthuma, D, Andlauer, T, Forstner, A, Streit, F, Baune, B, Air, T, Sinnamon, G, Wray, N, Macintyre, D, Porteous, D, Homuth, G, Rivera, M, Grove, J, Middeldorp, C, Hickie, I, Pergadia, M, Mehta, D, Smit, J, Jansen, R, De Geus, E, Dunn, E, Li, Q, Nauck, M, Schoevers, R, Beekman, A, Knowles, J, Viktorin, A, Arnold, P, Barr, C, Bedoya-Berrio, G, Joseph Bienvenu, O, Brentani, H, Burton, C, Camarena, B, Cappi, C, Cath, D, Cavallini, M, Cusi, D, Darrow, S, Denys, D, Derks, E, Dietrich, A, Fernandez, T, Figee, M, Freimer, N, Gerber, G, Grados, M, Greenberg, E, Hanna, G, Hartmann, A, Hirschtritt, M, Hoekstra, P, Huang, A, Huyser, C, Illmann, C, Jenike, M, Kuperman, S, Leventhal, B, Lochner, C, Lyon, G, Macciardi, F, Madruga-Garrido, M, Malaty, I, Maras, A, Mcgrath, L, Miguel, E, Mir, P, Nestadt, G, Nicolini, H, Okun, M, Pakstis, A, Paschou, P, Piacentini, J, Pittenger, C, Plessen, K, Ramensky, V, Ramos, E, Reus, V, Richter, M, Riddle, M, Robertson, M, Roessner, V, Rosário, M, Samuels, J, Sandor, P, Stein, D, Tsetsos, F, Van Nieuwerburgh, F, Weatherall, S, Wendland, J, Wolanczyk, T, Worbe, Y, Zai, G, Goes, F, Mclaughlin, N, Nestadt, P, Grabe, H, Depienne, C, Konkashbaev, A, Lanzagorta, N, Valencia-Duarte, A, Bramon, E, Buccola, N, Cahn, W, Cairns, M, Chong, S, Cohen, D, Crespo-Facorro, B, Crowley, J, Davidson, M, Delisi, L, Dinan, T, Donohoe, G, Drapeau, E, Duan, J, Haan, L, Hougaard, D, Karachanak-Yankova, S, Khrunin, A, Klovins, J, Kučinskas, V, Keong, J, Limborska, S, Loughland, C, Lönnqvist, J, Maher, B, Mattheisen, M, Mcdonald, C, Murphy, K, Nenadic, I, Van Os, J, Pantelis, C, Pato, M, Petryshen, T, Quested, D, Roussos, P, Sanders, A, Schall, U, Schwab, S, Sim, K, So, H, Stögmann, E, Subramaniam, M, Toncheva, D, Waddington, J, Walters, J, Weiser, M, Cheng, W, Cloninger, R, Curtis, D, Gejman, P, Henskens, F, Mattingsdal, M, Oh, S, Scott, R, Webb, B, Breen, G, Churchhouse, C, Bulik, C, Daly, M, Dichgans, M, Faraone, S, Guerreiro, R, Holmans, P, Kendler, K, Koeleman, B, Mathews, C, Price, A, Scharf, J, Sklar, P, Williams, J, Wood, N, Cotsapas, C, Palotie, A, Smoller, J, Sullivan, P, Rosand, J, Corvin, A, Neale, B, Kauwe, John S. K., Mcquillin, Andrew, Adams, Hieab H. H., Mccormack, Mark, Bau, Claiton H. D., Mcgough, James J., Mcintosh, Andrew, Andlauer, Till F. M., Macintyre, Donald J., Mcgrath, Lauren, Mclaughlin, Nicole, Delisi, Lynn, Mcdonald, Colm, Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement (Inserm U1167 - RID-AGE - Institut Pasteur), RIKEN Center for Integrative Medical Science, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), University of South Florida (USF), University of Zürich [Zürich] (UZH)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Alzheimer Precision Medicine GRC n°21 (APM), CHU Pitié-Salpêtrière [APHP], Cardiff University-Medical Research Council, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Johannes Kepler University Linz [linz] (JKU), Washington University in St Louis, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Universitat Autònoma de Barcelona [Barcelona] (UAB), Hôpital Erasme (Bruxelles), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Jagiellonian University [Krakow] (UJ), Technische Universität Dresden (TUD), National and Kapodistrian University of Athens = University of Athens (NKUA | UoA), Charles University [Prague], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), University of Bergen (UIB), University Medicine Goettingen, Università di Bologna [Bologna] (UNIBO), Forschungszentrum Jülich GmbH, UNSW Medicine [Sydney], McGill University, Universidad de Antioquia, University of Florida [Gainesville], Universiteit Gent [Ghent], Service Psychiatrie de l'Enfant et de l'Adolescent [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], University of Wollongong, Alzheimer Precision Medicine [CHU Pitié-Salpétriêre] (GRC 21 APM), Anttila, Verneri [0000-0002-0073-4675], Finucane, Hilary K [0000-0003-3864-9828], Walters, Raymond K [0000-0001-8422-6530], Duncan, Laramie [0000-0003-1131-661X], Escott-Price, Valentina [0000-0003-1784-5483], Falcone, Guido J [0000-0002-6407-0302], Gormley, Padhraig [0000-0002-8908-6968], Malik, Rainer [0000-0001-9212-2520], Ripke, Stephan [0000-0003-3622-835X], Wei, Zhi [0000-0001-6059-4267], Yu, Dongmei [0000-0001-7901-4365], Lee, Phil H [0000-0003-1770-3100], Breen, Gerome [0000-0003-2053-1792], Bulik, Cynthia M [0000-0001-7772-3264], Daly, Mark [0000-0002-0949-8752], Dichgans, Martin [0000-0002-0654-387X], Faraone, Stephen V [0000-0002-9217-3982], Holmans, Peter [0000-0003-0870-9412], Koeleman, Bobby [0000-0001-7749-182X], Mathews, Carol A [0000-0003-2208-7058], Sklar, Pamela [0000-0001-9715-4943], Williams, Julie [0000-0002-4069-0259], Wood, Nicholas W [0000-0002-9500-3348], Cotsapas, Chris [0000-0002-7772-5910], Smoller, Jordan W [0000-0002-0381-6334], Sullivan, Patrick [0000-0002-6619-873X], Rosand, Jonathan [0000-0002-1014-9138], Corvin, Aiden [0000-0001-6717-4089], Neale, Benjamin M [0000-0003-1513-6077], and Apollo - University of Cambridge Repository
Subjects: Etiology, [SDV]Life Sciences [q-bio], MESH: Brain Diseases, body-mass index, genetics [Mental Disorders], Disorders of the Brain, Risks factors, classification [Mental Disorders], MESH: Quantitative Trait, Heritable, MESH: Risk Factors, Risk Factors, MESH: Genetic Variation, alzheimers-disease, 610 Medicine & health, bipolar disorder, Brain Diseases, deficit hyperactivity disorder, Multidisciplinary, Mental Disorders, genetics [Brain Diseases], Brain Disease, Brain, Genetic Variation, Genome-Wide Association Study, Humans, Phenotype, Quantitative Trait, Heritable, Psychiatric Disorders, anorexia-nervosa, Mental Disorder, Psychiatric Genomics, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], long-term survival, Engineering sciences. Technology, Human, General Science & Technology, population-based twin, diagnosis [Mental Disorders], MESH: Phenotype, Neurological Disorders, Quantitative Trait, MD Multidisciplinary, MESH: Mental Disorders, diagnosis [Brain Diseases], Heritable, genetic correlations, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, major depressive disorder, Risk Factor, Brain Diseases/classification, Brain Diseases/diagnosis, Brain Diseases/genetics, Mental Disorders/classification, Mental Disorders/diagnosis, Mental Disorders/genetics, classification [Brain Diseases], Perturbações do Desenvolvimento Infantil e Saúde Mental, ddc:320, MESH: Genome-Wide Association Study, genome-wide association, Brainstorm Consortium, Genetic Factors, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities’ assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer’s disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important “scaffolding” to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders.
Published: 2018

19. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Wang, Sheng, primary, Mandell, Jeffrey D., additional, Kumar, Yogesh, additional, Sun, Nawei, additional, Morris, Montana T., additional, Arbelaez, Juan, additional, Nasello, Cara, additional, Dong, Shan, additional, Duhn, Clif, additional, Zhao, Xin, additional, Yang, Zhiyu, additional, Padmanabhuni, Shanmukha S., additional, Yu, Dongmei, additional, King, Robert A., additional, Dietrich, Andrea, additional, Khalifa, Najah, additional, Dahl, Niklas, additional, Huang, Alden Y., additional, Neale, Benjamin M., additional, Coppola, Giovanni, additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, Fernandez, Thomas V., additional, Buxbaum, Joseph D., additional, De Rubeis, Silvia, additional, Grice, Dorothy E., additional, Xing, Jinchuan, additional, Heiman, Gary A., additional, Tischfield, Jay A., additional, Paschou, Peristera, additional, Willsey, A. Jeremy, additional, State, Matthew W., additional, Abdulkadir, Mohamed, additional, Bodmer, Benjamin, additional, Bromberg, Yana, additional, Brown, Lawrence W., additional, Cheon, Keun-Ah, additional, Coffey, Barbara J., additional, Deng, Li, additional, Elzerman, Lonneke, additional, Fremer, Carolin, additional, Garcia-Delgar, Blanca, additional, Gilbert, Donald L., additional, Hagstrøm, Julie, additional, Hedderly, Tammy, additional, Heyman, Isobel, additional, Hoekstra, Pieter J., additional, Hong, Hyun Ju, additional, Huyser, Chaim, additional, Kim, Eun-Joo, additional, Kim, Young Key, additional, Kim, Young-Shin, additional, Koh, Yun-Joo, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L, additional, Ludolph, Andrea G., additional, Madruga-Garrido, Marcos, additional, Maras, Athanasios, additional, Mir, Pablo, additional, Morer, Astrid, additional, Morris, Montana T, additional, Müller-Vahl, Kirsten, additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Plessen, Kerstin J., additional, Poisner, Hannah, additional, Roessner, Veit, additional, Sanders, Stephan J., additional, Shin, Eun-Young, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Thackray, Joshua K., additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Wanderer, Sina, additional, Wang, Sheng, additional, Willsey, A Jeremy, additional, Woods, Martin, additional, Zhang, Yeting, additional, Zinner, Samuel H., additional, Androutsos, Christos, additional, Barta, Csaba, additional, Farkas, Luca, additional, Fichna, Jakub, additional, Georgitsi, Marianthi, additional, Janik, Piotr, additional, Karagiannidis, Iordanis, additional, Koumoula, Anastasia, additional, Nagy, Peter, additional, Puchala, Joanna, additional, Rizzo, Renata, additional, Szejko, Natalia, additional, Szymanska, Urszula, additional, Tarnok, Zsanett, additional, Tsironi, Vaia, additional, Wolanczyk, Tomasz, additional, Zekanowski, Cezary, additional, Barr, Cathy L., additional, Batterson, James R., additional, Berlin, Cheston, additional, Bruun, Ruth D., additional, Budman, Cathy L., additional, Cath, Danielle C., additional, Chouinard, Sylvain, additional, Cox, Nancy J., additional, Darrow, Sabrina, additional, Davis, Lea K., additional, Dion, Yves, additional, Freimer, Nelson B., additional, Grados, Marco A., additional, Hirschtritt, Matthew E., additional, Illmann, Cornelia, additional, Kurlan, Roger, additional, Leckman, James F., additional, Lyon, Gholson J., additional, Malaty, Irene A., additional, MacMahon, William M., additional, Okun, Michael S., additional, Osiecki, Lisa, additional, Pauls, David L., additional, Posthuma, Danielle, additional, Ramensky, Vasily, additional, Robertson, Mary M., additional, Rouleau, Guy A., additional, Sandor, Paul, additional, Singer, Harvey S., additional, Smit, Jan, additional, and Sul, Jae-Hoon, additional
Published: 2018
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20. 896. Genetic and Phenotypic Overlap of Specific Obsessive-Compulsive Subtypes with Tourette Syndrome

Author: Hirschtritt, Matthew, primary, Darrow, Sabrina M., additional, Illmann, Cornelia, additional, Osiecki, Lisa, additional, Grados, Marco, additional, Sandor, Paul, additional, Dion, Yves, additional, King, Robert A., additional, Pauls, David, additional, Budman, Cathy L., additional, Cath, Danielle C., additional, Greenberg, Erica, additional, Lyon, Gholson J., additional, Yu, Dongmei, additional, McGrath, Lauren M., additional, McMahon, William M., additional, Lee, Paul C., additional, Delucchi, Kevin L., additional, Scharf, Jeremiah M., additional, and Mathews, Carol A., additional
Published: 2017
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21. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

Author: Willsey, A. Jeremy, primary, Fernandez, Thomas V., additional, Yu, Dongmei, additional, King, Robert A., additional, Dietrich, Andrea, additional, Xing, Jinchuan, additional, Sanders, Stephan J., additional, Mandell, Jeffrey D., additional, Huang, Alden Y., additional, Richer, Petra, additional, Smith, Louw, additional, Dong, Shan, additional, Samocha, Kaitlin E., additional, Neale, Benjamin M., additional, Coppola, Giovanni, additional, Mathews, Carol A., additional, Tischfield, Jay A., additional, Scharf, Jeremiah M., additional, State, Matthew W., additional, Heiman, Gary A., additional, Abdulkadir, Mohamed, additional, Bohnenpoll, Julia, additional, Bromberg, Yana, additional, Brown, Lawrence W., additional, Cheon, Keun-Ah, additional, Coffey, Barbara J., additional, Deng, Li, additional, Elzerman, Lonneke, additional, Fründt, Odette, additional, Garcia-Delgar, Blanca, additional, Gedvilaite, Erika, additional, Gilbert, Donald L., additional, Grice, Dorothy E., additional, Hagstrøm, Julie, additional, Hedderly, Tammy, additional, Heyman, Isobel, additional, Hoekstra, Pieter J., additional, Hong, Hyun Ju, additional, Huyser, Chaim, additional, Ibanez-Gomez, Laura, additional, Kim, Young Key, additional, Kim, Young-Shin, additional, Koh, Yun-Joo, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Lamerz, Andreas, additional, Leventhal, Bennett, additional, Ludolph, Andrea G., additional, Lühr da Silva, Claudia, additional, Madruga-Garrido, Marcos, additional, Maras, Athanasios, additional, Mir, Pablo, additional, Morer, Astrid, additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Nasello, Cara, additional, Openneer, Thaïra J.C., additional, Plessen, Kerstin J., additional, Roessner, Veit, additional, Sanders, Stephan, additional, Shin, Eun-Young, additional, Sival, Deborah A., additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Stolte, Anne Marie, additional, Sun, Nawei, additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Walker, Michael F., additional, Wanderer, Sina, additional, Wang, Shuoguo, additional, Willsey, A. Jeremy, additional, Woods, Martin, additional, Zhang, Yeting, additional, Zhou, Anbo, additional, Zinner, Samuel H., additional, Barr, Cathy L., additional, Batterson, James R., additional, Berlin, Cheston, additional, Bruun, Ruth D., additional, Budman, Cathy L., additional, Cath, Danielle C., additional, Chouinard, Sylvain, additional, Cox, Nancy J., additional, Darrow, Sabrina, additional, Davis, Lea K., additional, Dion, Yves, additional, Freimer, Nelson B., additional, Grados, Marco A., additional, Hirschtritt, Matthew E., additional, Illmann, Cornelia, additional, Kurlan, Roger, additional, Leckman, James F., additional, Lyon, Gholson J., additional, Malaty, Irene A., additional, MaMahon, William M., additional, Okun, Michael S., additional, Osiecki, Lisa, additional, Pauls, David L., additional, Posthuma, Danielle, additional, Ramensky, Vasily, additional, Robertson, Mary M., additional, Rouleau, Guy A., additional, Sandor, Paul, additional, Singer, Harvey S., additional, Smit, Jan, additional, and Sul, Jae-Hoon, additional
Published: 2017
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22. Lifetime Prevalence, Age of Risk, and Etiology of Comorbid Psychiatric Disorders in Tourette Syndrome

Author: Hirschtritt, Matthew E., Lee, Paul C., Pauls, David L., Dion, Yves, Grados, Marco A., Illmann, Cornelia, King, Robert A., Sandor, Paul, McMahon, William M., Lyon, Gholson J., Cath, Danielle C., Kurlan, Roger, Robertson, Mary M., Osiecki, Lisa, Scharf, Jeremiah M., and Mathews, Carol A.
Subjects: Male, Canada, Adolescent, Mental Disorders, Age Factors, Comorbidity, Article, United Kingdom, United States, Young Adult, Age Distribution, Risk Factors, Child, Preschool, Prevalence, Humans, Female, Age of Onset, Child, Netherlands, Tourette Syndrome
Abstract: Tourette syndrome (TS) is characterized by high rates of psychiatric comorbidity; however, few studies have fully characterized these comorbidities. Furthermore, most studies have included relatively few participants (200), and none has examined the ages of highest risk for each TS-associated comorbidity or their etiologic relationship to TS.To characterize the lifetime prevalence, clinical associations, ages of highest risk, and etiology of psychiatric comorbidity among individuals with TS.Cross-sectional structured diagnostic interviews conducted between April 1, 1992, and December 31, 2008, of participants with TS (n = 1374) and TS-unaffected family members (n = 1142).Lifetime prevalence of comorbid DSM-IV-TR disorders, their heritabilities, ages of maximal risk, and associations with symptom severity, age at onset, and parental psychiatric history.The lifetime prevalence of any psychiatric comorbidity among individuals with TS was 85.7%; 57.7% of the population had 2 or more psychiatric disorders. The mean (SD) number of lifetime comorbid diagnoses was 2.1 (1.6); the mean number was 0.9 (1.3) when obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) were excluded, and 72.1% of the individuals met the criteria for OCD or ADHD. Other disorders, including mood, anxiety, and disruptive behavior, each occurred in approximately 30% of the participants. The age of greatest risk for the onset of most comorbid psychiatric disorders was between 4 and 10 years, with the exception of eating and substance use disorders, which began in adolescence (interquartile range, 15-19 years for both). Tourette syndrome was associated with increased risk of anxiety (odds ratio [OR], 1.4; 95% CI, 1.0-1.9; P = .04) and decreased risk of substance use disorders (OR, 0.6; 95% CI, 0.3-0.9; P = .02) independent from comorbid OCD and ADHD; however, high rates of mood disorders among participants with TS (29.8%) may be accounted for by comorbid OCD (OR, 3.7; 95% CI, 2.9-4.8; P .001). Parental history of ADHD was associated with a higher burden of non-OCD, non-ADHD comorbid psychiatric disorders (OR, 1.86; 95% CI, 1.32-2.61; P .001). Genetic correlations between TS and mood (RhoG, 0.47), anxiety (RhoG, 0.35), and disruptive behavior disorders (RhoG, 0.48), may be accounted for by ADHD and, for mood disorders, by OCD.This study is, to our knowledge, the most comprehensive of its kind. It confirms the belief that psychiatric comorbidities are common among individuals with TS, demonstrates that most comorbidities begin early in life, and indicates that certain comorbidities may be mediated by the presence of comorbid OCD or ADHD. In addition, genetic analyses suggest that some comorbidities may be more biologically related to OCD and/or ADHD rather than to TS.
Published: 2015

23. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

Author: Yu, Dongmei, Mathews, Carol A., Scharf, Jeremiah M., Neale, Benjamin M., Davis, Lea K., Gamazon, Eric R., Derks, Eske M., Evans, Patrick, Edlund, Christopher K., Crane, Jacquelyn, Fagerness, Jesen A., Osiecki, Lisa, Gallagher, Patience, Gerber, Gloria, Haddad, Stephen, Illmann, Cornelia, McGrath, Lauren M., Mayerfeld, Catherine, Arepalli, Sampath, Barlassina, Cristina, Barr, Cathy L., Bellodi, Laura, Benarroch, Fortu, Berrió, Gabriel Bedoya, Bienvenu, O. Joseph, Black, Donald, Bloch, Michael H., Brentani, Helena, Bruun, Ruth D., Budman, Cathy L., Camarena, Beatriz, Campbell, Desmond D., Cappi, Carolina, Cardona Silgado, Julio C., Cavallini, Maria C., Chavira, Denise A., Chouinard, Sylvain, Cook, Edwin H., Cookson, M. R., Coric, Vladimir, Cullen, Bernadette, Cusi, Daniele, Delorme, Richard, Denys, Damiaan, Dion, Yves, Eapen, Valsama, Egberts, Karin, Falkai, Peter, Fernandez, Thomas, Fournier, Eduardo, Garrido, Helena, Geller, Daniel, Gilbert, Donald, Girard, Simon L., Grabe, Hans J., Grados, Marco A., Greenberg, Benjamin D., Gross-Tsur, Varda, Grünblatt, Edna, Hardy, John, Heiman, Gary A., Hemmings, Sian M.J., Herrera, Luis D., Hezel, Dianne M., Hoekstra, Pieter J., Jankovic, Joseph, Kennedy, James L., King, Robert A., Konkashbaev, Anuar I., Kremeyer, Barbara, Kurlan, Roger, Lanzagorta, Nuria, Leboyer, Marion, Leckman, James F., Lennertz, Leonhard, Liu, Chunyu, Lochner, Christine, Lowe, Thomas L., Lupoli, Sara, Macciardi, Fabio, Maier, Wolfgang, Manunta, Paolo, Marconi, Maurizio, McCracken, James T., Mesa Restrepo, Sandra C., Moessner, Rainald, Moorjani, Priya, Morgan, Jubel, Muller, Heike, Murphy, Dennis L., Naarden, Allan L., Ochoa, William Cornejo, Ophoff, Roel A., Pakstis, Andrew J., Pato, Michele T., Pato, Carlos N., Piacentini, John, Pittenger, Christopher, Pollak, Yehuda, Rauch, Scott L., Renner, Tobias, Reus, Victor I., Richter, Margaret A., Riddle, Mark A., Robertson, Mary M., Romero, Roxana, Rosário, Maria C., Rosenberg, David, Ruhrmann, Stephan, Sabatti, Chiara, Salvi, Erika, Sampaio, Aline S., Samuels, Jack, Sandor, Paul, Service, Susan K., Sheppard, Brooke, Singer, Harvey S., Smit, Jan H., Stein, Dan J., Strengman, Eric, Tischfield, Jay A., Turiel, Maurizio, Valencia Duarte, Ana V., Vallada, Homero, Veenstra-VanderWeele, Jeremy, Walitza, Susanne, Walkup, John, Wang, Ying, Weale, Mike, Weiss, Robert, Wendland, Jens R., Westenberg, Herman G.M., Yao, Yin, Hounie, Ana G., Miguel, Euripedes C., Nicolini, Humberto, Wagner, Michael, Ruiz-Linares, Andres, Cath, Danielle C., McMahon, William, Posthuma, Danielle, Oostra, Ben A., Nestadt, Gerald, Rouleau, Guy A., Purcell, Shaun, Jenike, Michael A., Heutink, Peter, Hanna, Gregory L., Conti, David V., Arnold, Paul D., Freimer, Nelson, Stewart, S. Evelyn, Knowles, James A., Cox, Nancy J., and Pauls, David L.
Subjects: Adult, Male, Psychiatric Status Rating Scales, Obsessive-Compulsive Disorder, Comorbidity, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Severity of Illness Index, Article, mental disorders, Humans, Female, Genome-Wide Association Study, Tourette Syndrome
Abstract: Obsessive-compulsive disorder (OCD) and Tourette's syndrome are highly heritable neurodevelopmental disorders that are thought to share genetic risk factors. However, the identification of definitive susceptibility genes for these etiologically complex disorders remains elusive. The authors report a combined genome-wide association study (GWAS) of Tourette's syndrome and OCD.The authors conducted a GWAS in 2,723 cases (1,310 with OCD, 834 with Tourette's syndrome, 579 with OCD plus Tourette's syndrome/chronic tics), 5,667 ancestry-matched controls, and 290 OCD parent-child trios. GWAS summary statistics were examined for enrichment of functional variants associated with gene expression levels in brain regions. Polygenic score analyses were conducted to investigate the genetic architecture within and across the two disorders.Although no individual single-nucleotide polymorphisms (SNPs) achieved genome-wide significance, the GWAS signals were enriched for SNPs strongly associated with variations in brain gene expression levels (expression quantitative loci, or eQTLs), suggesting the presence of true functional variants that contribute to risk of these disorders. Polygenic score analyses identified a significant polygenic component for OCD (p=2×10(-4)), predicting 3.2% of the phenotypic variance in an independent data set. In contrast, Tourette's syndrome had a smaller, nonsignificant polygenic component, predicting only 0.6% of the phenotypic variance (p=0.06). No significant polygenic signal was detected across the two disorders, although the sample is likely underpowered to detect a modest shared signal. Furthermore, the OCD polygenic signal was significantly attenuated when cases with both OCD and co-occurring Tourette's syndrome/chronic tics were included in the analysis (p=0.01).Previous work has shown that Tourette's syndrome and OCD have some degree of shared genetic variation. However, the data from this study suggest that there are also distinct components to the genetic architectures of these two disorders. Furthermore, OCD with co-occurring Tourette's syndrome/chronic tics may have different underlying genetic susceptibility compared with OCD alone.
Published: 2014

24. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome

Author: Huang, Alden Y., primary, Yu, Dongmei, additional, Davis, Lea K., additional, Sul, Jae-Hoon, additional, Tsetsos, Fotis, additional, Ramensky, Vasily, additional, Zelaya, Ivette, additional, Ramos, Eliana Marisa, additional, Osiecki, Lisa, additional, Chen, Jason A., additional, McGrath, Lauren M., additional, Illmann, Cornelia, additional, Sandor, Paul, additional, Barr, Cathy L., additional, Grados, Marco, additional, Singer, Harvey S., additional, Noethen, Markus M., additional, Hebebrand, Johannes, additional, King, Robert A., additional, Dion, Yves, additional, Rouleau, Guy, additional, Budman, Cathy L., additional, Depienne, Christel, additional, Worbe, Yulia, additional, Hartmann, Andreas, additional, Muller-Vahl, Kirsten R., additional, Stuhrmann, Manfred, additional, Aschauer, Harald, additional, Stamenkovic, Mara, additional, Schloegelhofer, Monika, additional, Konstantinidis, Anastasios, additional, Lyon, Gholson J., additional, McMahon, William M., additional, Barta, Csaba, additional, Tarnok, Zsanett, additional, Nagy, Peter, additional, Batterson, James R., additional, Rizzo, Renata, additional, Cath, Danielle C., additional, Wolanczyk, Tomasz, additional, Berlin, Cheston, additional, Malaty, Irene A., additional, Okun, Michael S., additional, Woods, Douglas W., additional, Rees, Elliott, additional, Pato, Carlos N., additional, Pato, Michele T., additional, Knowles, James A, additional, Posthuma, Danielle, additional, Pauls, David L., additional, Cox, Nancy J., additional, Neale, Benjamin M., additional, Freimer, Nelson B., additional, Paschou, Peristera, additional, Mathews, Carol A., additional, Scharf, Jeremiah M., additional, and Coppola, Giovanni, additional
Published: 2016
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25. De NovoSequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

Author: Wang, Sheng, Mandell, Jeffrey D., Kumar, Yogesh, Sun, Nawei, Morris, Montana T., Arbelaez, Juan, Nasello, Cara, Dong, Shan, Duhn, Clif, Zhao, Xin, Yang, Zhiyu, Padmanabhuni, Shanmukha S., Yu, Dongmei, King, Robert A., Dietrich, Andrea, Khalifa, Najah, Dahl, Niklas, Huang, Alden Y., Neale, Benjamin M., Coppola, Giovanni, Mathews, Carol A., Scharf, Jeremiah M., Abdulkadir, Mohamed, Arbelaez, Juan, Bodmer, Benjamin, Bromberg, Yana, Brown, Lawrence W., Cheon, Keun-Ah, Coffey, Barbara J., Deng, Li, Dietrich, Andrea, Dong, Shan, Duhn, Clif, Elzerman, Lonneke, Fernandez, Thomas V., Fremer, Carolin, Garcia-Delgar, Blanca, Gilbert, Donald L., Grice, Dorothy E., Hagstrøm, Julie, Hedderly, Tammy, Heiman, Gary A., Heyman, Isobel, Hoekstra, Pieter J., Hong, Hyun Ju, Huyser, Chaim, Kim, Eun-Joo, Kim, Young Key, Kim, Young-Shin, King, Robert A., Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett L, Ludolph, Andrea G., Madruga-Garrido, Marcos, Mandell, Jeffrey D., Maras, Athanasios, Mir, Pablo, Morer, Astrid, Morris, Montana T, Müller-Vahl, Kirsten, Münchau, Alexander, Murphy, Tara L., Nasello, Cara, Plessen, Kerstin J., Poisner, Hannah, Roessner, Veit, Sanders, Stephan J., Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, State, Matthew W., Sun, Nawei, Thackray, Joshua K., Tischfield, Jay A., Tübing, Jennifer, Visscher, Frank, Wanderer, Sina, Wang, Sheng, Willsey, A Jeremy, Woods, Martin, Xing, Jinchuan, Zhang, Yeting, Zhao, Xin, Zinner, Samuel H., Androutsos, Christos, Barta, Csaba, Farkas, Luca, Fichna, Jakub, Georgitsi, Marianthi, Janik, Piotr, Karagiannidis, Iordanis, Koumoula, Anastasia, Nagy, Peter, Paschou, Peristera, Puchala, Joanna, Rizzo, Renata, Szejko, Natalia, Szymanska, Urszula, Tarnok, Zsanett, Tsironi, Vaia, Wolanczyk, Tomasz, Zekanowski, Cezary, Barr, Cathy L., Batterson, James R., Berlin, Cheston, Bruun, Ruth D., Budman, Cathy L., Cath, Danielle C., Chouinard, Sylvain, Coppola, Giovanni, Cox, Nancy J., Darrow, Sabrina, Davis, Lea K., Dion, Yves, Freimer, Nelson B., Grados, Marco A., Hirschtritt, Matthew E., Huang, Alden Y., Illmann, Cornelia, King, Robert A., Kurlan, Roger, Leckman, James F., Lyon, Gholson J., Malaty, Irene A., Mathews, Carol A., MacMahon, William M., Neale, Benjamin M., Okun, Michael S., Osiecki, Lisa, Pauls, David L., Posthuma, Danielle, Ramensky, Vasily, Robertson, Mary M., Rouleau, Guy A., Sandor, Paul, Scharf, Jeremiah M., Singer, Harvey S., Smit, Jan, Sul, Jae-Hoon, Yu, Dongmei, Fernandez, Thomas V., Buxbaum, Joseph D., De Rubeis, Silvia, Grice, Dorothy E., Xing, Jinchuan, Heiman, Gary A., Tischfield, Jay A., Paschou, Peristera, Willsey, A. Jeremy, and State, Matthew W.
Abstract: We previously established the contribution of de novodamaging sequence variants to Tourette disorder (TD) through whole-exome sequencing of 511 trios. Here, we sequence an additional 291 TD trios and analyze the combined set of 802 trios. We observe an overrepresentation of de novodamaging variants in simplex, but not multiplex, families; we identify a high-confidence TD risk gene, CELSR3(cadherin EGF LAG seven-pass G-type receptor 3); we find that the genes mutated in TD patients are enriched for those related to cell polarity, suggesting a common pathway underlying pathobiology; and we confirm a statistically significant excess of de novocopy number variants in TD. Finally, we identify significant overlap of de novosequence variants between TD and obsessive-compulsive disorder and de novocopy number variants between TD and autism spectrum disorder, consistent with shared genetic risk.
Published: 2018
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26. Analysis of shared heritability in common disorders of the brain.

Author: Anttila V, Bulik-Sullivan B, Finucane HK, Walters RK, Bras J, Duncan L, Escott-Price V, Falcone GJ, Gormley P, Malik R, Patsopoulos NA, Ripke S, Wei Z, Yu D, Lee PH, Turley P, Grenier-Boley B, Chouraki V, Kamatani Y, Berr C, Letenneur L, Hannequin D, Amouyel P, Boland A, Deleuze JF, Duron E, Vardarajan BN, Reitz C, Goate AM, Huentelman MJ, Kamboh MI, Larson EB, Rogaeva E, St George-Hyslop P, Hakonarson H, Kukull WA, Farrer LA, Barnes LL, Beach TG, Demirci FY, Head E, Hulette CM, Jicha GA, Kauwe JSK, Kaye JA, Leverenz JB, Levey AI, Lieberman AP, Pankratz VS, Poon WW, Quinn JF, Saykin AJ, Schneider LS, Smith AG, Sonnen JA, Stern RA, Van Deerlin VM, Van Eldik LJ, Harold D, Russo G, Rubinsztein DC, Bayer A, Tsolaki M, Proitsi P, Fox NC, Hampel H, Owen MJ, Mead S, Passmore P, Morgan K, Nöthen MM, Rossor M, Lupton MK, Hoffmann P, Kornhuber J, Lawlor B, McQuillin A, Al-Chalabi A, Bis JC, Ruiz A, Boada M, Seshadri S, Beiser A, Rice K, van der Lee SJ, De Jager PL, Geschwind DH, Riemenschneider M, Riedel-Heller S, Rotter JI, Ransmayr G, Hyman BT, Cruchaga C, Alegret M, Winsvold B, Palta P, Farh KH, Cuenca-Leon E, Furlotte N, Kurth T, Ligthart L, Terwindt GM, Freilinger T, Ran C, Gordon SD, Borck G, Adams HHH, Lehtimäki T, Wedenoja J, Buring JE, Schürks M, Hrafnsdottir M, Hottenga JJ, Penninx B, Artto V, Kaunisto M, Vepsäläinen S, Martin NG, Montgomery GW, Kurki MI, Hämäläinen E, Huang H, Huang J, Sandor C, Webber C, Muller-Myhsok B, Schreiber S, Salomaa V, Loehrer E, Göbel H, Macaya A, Pozo-Rosich P, Hansen T, Werge T, Kaprio J, Metspalu A, Kubisch C, Ferrari MD, Belin AC, van den Maagdenberg AMJM, Zwart JA, Boomsma D, Eriksson N, Olesen J, Chasman DI, Nyholt DR, Avbersek A, Baum L, Berkovic S, Bradfield J, Buono RJ, Catarino CB, Cossette P, De Jonghe P, Depondt C, Dlugos D, Ferraro TN, French J, Hjalgrim H, Jamnadas-Khoda J, Kälviäinen R, Kunz WS, Lerche H, Leu C, Lindhout D, Lo W, Lowenstein D, McCormack M, Møller RS, Molloy A, Ng PW, Oliver K, Privitera M, Radtke R, Ruppert AK, Sander T, Schachter S, Schankin C, Scheffer I, Schoch S, Sisodiya SM, Smith P, Sperling M, Striano P, Surges R, Thomas GN, Visscher F, Whelan CD, Zara F, Heinzen EL, Marson A, Becker F, Stroink H, Zimprich F, Gasser T, Gibbs R, Heutink P, Martinez M, Morris HR, Sharma M, Ryten M, Mok KY, Pulit S, Bevan S, Holliday E, Attia J, Battey T, Boncoraglio G, Thijs V, Chen WM, Mitchell B, Rothwell P, Sharma P, Sudlow C, Vicente A, Markus H, Kourkoulis C, Pera J, Raffeld M, Silliman S, Boraska Perica V, Thornton LM, Huckins LM, William Rayner N, Lewis CM, Gratacos M, Rybakowski F, Keski-Rahkonen A, Raevuori A, Hudson JI, Reichborn-Kjennerud T, Monteleone P, Karwautz A, Mannik K, Baker JH, O'Toole JK, Trace SE, Davis OSP, Helder SG, Ehrlich S, Herpertz-Dahlmann B, Danner UN, van Elburg AA, Clementi M, Forzan M, Docampo E, Lissowska J, Hauser J, Tortorella A, Maj M, Gonidakis F, Tziouvas K, Papezova H, Yilmaz Z, Wagner G, Cohen-Woods S, Herms S, Julià A, Rabionet R, Dick DM, Ripatti S, Andreassen OA, Espeseth T, Lundervold AJ, Steen VM, Pinto D, Scherer SW, Aschauer H, Schosser A, Alfredsson L, Padyukov L, Halmi KA, Mitchell J, Strober M, Bergen AW, Kaye W, Szatkiewicz JP, Cormand B, Ramos-Quiroga JA, Sánchez-Mora C, Ribasés M, Casas M, Hervas A, Arranz MJ, Haavik J, Zayats T, Johansson S, Williams N, Dempfle A, Rothenberger A, Kuntsi J, Oades RD, Banaschewski T, Franke B, Buitelaar JK, Arias Vasquez A, Doyle AE, Reif A, Lesch KP, Freitag C, Rivero O, Palmason H, Romanos M, Langley K, Rietschel M, Witt SH, Dalsgaard S, Børglum AD, Waldman I, Wilmot B, Molly N, Bau CHD, Crosbie J, Schachar R, Loo SK, McGough JJ, Grevet EH, Medland SE, Robinson E, Weiss LA, Bacchelli E, Bailey A, Bal V, Battaglia A, Betancur C, Bolton P, Cantor R, Celestino-Soper P, Dawson G, De Rubeis S, Duque F, Green A, Klauck SM, Leboyer M, Levitt P, Maestrini E, Mane S, De-Luca DM, Parr J, Regan R, Reichenberg A, Sandin S, Vorstman J, Wassink T, Wijsman E, Cook E, Santangelo S, Delorme R, Rogé B, Magalhaes T, Arking D, Schulze TG, Thompson RC, Strohmaier J, Matthews K, Melle I, Morris D, Blackwood D, McIntosh A, Bergen SE, Schalling M, Jamain S, Maaser A, Fischer SB, Reinbold CS, Fullerton JM, Guzman-Parra J, Mayoral F, Schofield PR, Cichon S, Mühleisen TW, Degenhardt F, Schumacher J, Bauer M, Mitchell PB, Gershon ES, Rice J, Potash JB, Zandi PP, Craddock N, Ferrier IN, Alda M, Rouleau GA, Turecki G, Ophoff R, Pato C, Anjorin A, Stahl E, Leber M, Czerski PM, Cruceanu C, Jones IR, Posthuma D, Andlauer TFM, Forstner AJ, Streit F, Baune BT, Air T, Sinnamon G, Wray NR, MacIntyre DJ, Porteous D, Homuth G, Rivera M, Grove J, Middeldorp CM, Hickie I, Pergadia M, Mehta D, Smit JH, Jansen R, de Geus E, Dunn E, Li QS, Nauck M, Schoevers RA, Beekman AT, Knowles JA, Viktorin A, Arnold P, Barr CL, Bedoya-Berrio G, Bienvenu OJ, Brentani H, Burton C, Camarena B, Cappi C, Cath D, Cavallini M, Cusi D, Darrow S, Denys D, Derks EM, Dietrich A, Fernandez T, Figee M, Freimer N, Gerber G, Grados M, Greenberg E, Hanna GL, Hartmann A, Hirschtritt ME, Hoekstra PJ, Huang A, Huyser C, Illmann C, Jenike M, Kuperman S, Leventhal B, Lochner C, Lyon GJ, Macciardi F, Madruga-Garrido M, Malaty IA, Maras A, McGrath L, Miguel EC, Mir P, Nestadt G, Nicolini H, Okun MS, Pakstis A, Paschou P, Piacentini J, Pittenger C, Plessen K, Ramensky V, Ramos EM, Reus V, Richter MA, Riddle MA, Robertson MM, Roessner V, Rosário M, Samuels JF, Sandor P, Stein DJ, Tsetsos F, Van Nieuwerburgh F, Weatherall S, Wendland JR, Wolanczyk T, Worbe Y, Zai G, Goes FS, McLaughlin N, Nestadt PS, Grabe HJ, Depienne C, Konkashbaev A, Lanzagorta N, Valencia-Duarte A, Bramon E, Buccola N, Cahn W, Cairns M, Chong SA, Cohen D, Crespo-Facorro B, Crowley J, Davidson M, DeLisi L, Dinan T, Donohoe G, Drapeau E, Duan J, Haan L, Hougaard D, Karachanak-Yankova S, Khrunin A, Klovins J, Kučinskas V, Lee Chee Keong J, Limborska S, Loughland C, Lönnqvist J, Maher B, Mattheisen M, McDonald C, Murphy KC, Nenadic I, van Os J, Pantelis C, Pato M, Petryshen T, Quested D, Roussos P, Sanders AR, Schall U, Schwab SG, Sim K, So HC, Stögmann E, Subramaniam M, Toncheva D, Waddington J, Walters J, Weiser M, Cheng W, Cloninger R, Curtis D, Gejman PV, Henskens F, Mattingsdal M, Oh SY, Scott R, Webb B, Breen G, Churchhouse C, Bulik CM, Daly M, Dichgans M, Faraone SV, Guerreiro R, Holmans P, Kendler KS, Koeleman B, Mathews CA, Price A, Scharf J, Sklar P, Williams J, Wood NW, Cotsapas C, Palotie A, Smoller JW, Sullivan P, Rosand J, Corvin A, Neale BM, Schott JM, Anney R, Elia J, Grigoroiu-Serbanescu M, Edenberg HJ, and Murray R
Subjects: Brain Diseases classification, Brain Diseases diagnosis, Genetic Variation, Genome-Wide Association Study, Humans, Mental Disorders classification, Mental Disorders diagnosis, Phenotype, Quantitative Trait, Heritable, Risk Factors, Brain Diseases genetics, Mental Disorders genetics
Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Published: 2018
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26 results on '"Illmann, Cornelia"'

1. Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

2. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

3. Synaptic processes and immune-related pathways implicated in Tourette syndrome.

4. Relationship between adverse childhood experiences and symptom severity in adult men with Tourette Syndrome

5. Interrogating the Genetic Determinants of Tourette’s Syndrome and Other Tic Disorders Through Genome-Wide Association Studies

6. Prevalence and predictors of hair pulling disorder and excoriation disorder in Tourette syndrome

7. Autism Spectrum Symptoms in a Tourette's Disorder Sample.

8. Rare Copy Number Variants in NRXN1 and CNTN6 Increase Risk for Tourette Syndrome.

9. Identification of Two Heritable Cross-Disorder Endophenotypes for Tourette Syndrome.

10. Social disinhibition is a heritable subphenotype of tics in Tourette syndrome.

11. Lifetime prevalence, age of risk, and genetic relationships of comorbid psychiatric disorders in Tourette syndrome.

12. Cross-disorder genome-wide analyses suggest a complex genetic relationship between Tourette's syndrome and OCD.

13. Copy Number Variation in Obsessive-Compulsive Disorder and Tourette Syndrome: A Cross-Disorder Study

14. Genome-wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome

15. Web-based phenotyping for Tourette Syndrome: Reliability of common co-morbid diagnoses

16. Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?

17. Synaptic processes and immune-related pathways implicated in Tourette Syndrome

18. Analysis of shared heritability in common disorders of the brain

19. De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

20. 896. Genetic and Phenotypic Overlap of Specific Obsessive-Compulsive Subtypes with Tourette Syndrome

21. De Novo Coding Variants Are Strongly Associated with Tourette Disorder

22. Lifetime Prevalence, Age of Risk, and Etiology of Comorbid Psychiatric Disorders in Tourette Syndrome

23. Cross-Disorder Genome-Wide Analyses Suggest a Complex Genetic Relationship Between Tourette Syndrome and Obsessive-Compulsive Disorder

24. Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome

25. De NovoSequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis

26. Analysis of shared heritability in common disorders of the brain.

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26 results on '"Illmann, Cornelia"'

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