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1. Fine Motor Skills in Children with Tourette Syndrome and their Unaffected First-degree Siblings

Author

Tygesen Marie Louise Boeg, Maigaard Katrine, Hagstrøm Julie, Skov Liselotte, Plessen Kerstin Jessica, and Debes Nanette Marinette Monique

Subjects
tourette syndrome, fine motor skills, adhd, neurodevelopment, Psychiatry, RC435-571, Psychology, BF1-990
Abstract

The exact etiology of Tourette Syndrome (TS) remains unclear, making the search for impaired neuropsychological functions possibly connected to the underlying cause of TS as important as it is challenging. One neuropsychological domain of interest is fine motor skills.

Published
2023
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2. Investigation of gene-environment interactions in relation to tic severity.

Author

Abdulkadir, Mohamed, Yu, Dongmei, Osiecki, Lisa, King, Robert A, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Plessen, Kerstin J, Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Visscher, Frank, Zinner, Samuel H, Mathews, Carol A, Scharf, Jeremiah M, Tischfield, Jay A, Heiman, Gary A, Dietrich, Andrea, and Hoekstra, Pieter J

Subjects
Humans, Tourette Syndrome, Tics, Severity of Illness Index, Attention Deficit Disorder with Hyperactivity, Pregnancy, Female, Genome-Wide Association Study, Gene-Environment Interaction, Autism Spectrum Disorder, Gene–environment interaction, Pre- and perinatal complications, Tic severity, Tourette syndrome, Mental Health, Autism, Genetics, Pediatric, Neurosciences, Serious Mental Illness, Brain Disorders, Human Genome, Neurodegenerative, Intellectual and Developmental Disabilities (IDD), Aetiology, 2.1 Biological and endogenous factors, Mental health, Gene-environment interaction, Psychology, Neurology & Neurosurgery
Abstract

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies.

Published
2021

3. Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Author

Cao, Xiaolong, Zhang, Yeting, Abdulkadir, Mohamed, Deng, Li, Fernandez, Thomas V, Garcia-Delgar, Blanca, Hagstrøm, Julie, Hoekstra, Pieter J, King, Robert A, Koesterich, Justin, Kuperman, Samuel, Morer, Astrid, Nasello, Cara, Plessen, Kerstin J, Thackray, Joshua K, Zhou, Lisheng, Dietrich, Andrea, Tischfield, Jay A, Heiman, Gary A, and Xing, Jinchuan

Subjects
Human Genome, Brain Disorders, Genetics, Clinical Research, Biotechnology, Neurosciences, Genetic Testing, Aetiology, 2.1 Biological and endogenous factors, Cadherin Related Proteins, Family, Genetic Predisposition to Disease, Humans, Nerve Tissue Proteins, Pedigree, Serine Endopeptidases, Tourette Syndrome, Exome Sequencing, Tourette International Collaborative Genetics Study, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

Tourette's Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein-protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.

Published
2021

4. Adverse events in cognitive behavioral therapy and relaxation training for children and adolescents with obsessive-compulsive disorder: A mixed methods study and analysis plan for the TECTO trial

Author

Pretzmann, Linea, Christensen, Sofie Heidenheim, Bryde Christensen, Anne, Funch Uhre, Camilla, Uhre, Valdemar, Thoustrup, Christine Lykke, Clemmesen, Iben Thiemer, Gudmandsen, Tin Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Olsen, Markus Harboe, Clemmensen, Line Katrine Harder, Lindschou, Jane, Gluud, Christian, Thomsen, Per Hove, Vangkilde, Signe, Hagstrøm, Julie, Rozental, Alexander, Jeppesen, Pia, Verhulst, Frank, Hybel, Katja Anna, Lønfeldt, Nicole Nadine, Plessen, Kerstin Jessica, Poulsen, Stig, and Pagsberg, Anne Katrine

Published
2023
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5. Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents (the TECTO trial): a statistical analysis plan for the randomised clinical trial

Author

Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Engstrøm, Janus, Lindschou, Jane, Siebner, Hartwig Roman, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Thomsen, Per Hove, Hybel, Katja, Clemmesen, Line Katrine Harder, Gluud, Christian, Plessen, Kerstin Jessica, Pagsberg, Anne Katrine, and Jakobsen, Janus Christian

Published
2022
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6. Correction: Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Published
2022
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7. Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmesen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Published
2022
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8. Pre- and perinatal complications in relation to Tourette syndrome and co-occurring obsessive-compulsive disorder and attention-deficit/hyperactivity disorder

Author

Abdulkadir, Mohamed, Tischfield, Jay A, King, Robert A, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, de Bruijn, Sebastian FTM, Elzerman, Lonneke, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hagstrøm, Julie, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Kim, Young Key, Kim, Young-Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Lamerz, Andreas, Leventhal, Bennett, Ludolph, Andrea G, Madruga-Garrido, Marcos, Maras, Athanasios, Messchendorp, Marieke D, Mir, Pablo, Morer, Astrid, Münchau, Alexander, Murphy, Tara L, Openneer, Thaïra JC, Plessen, Kerstin J, Rath, Judith JG, Roessner, Veit, Fründt, Odette, Shin, Eun-Young, Sival, Deborah A, Song, Dong-Ho, Song, Jungeun, Stolte, Anne-Marie, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H, State, Matthew W, Heiman, Gary A, Hoekstra, Pieter J, and Dietrich, Andrea

Subjects
Clinical and Health Psychology, Biomedical and Clinical Sciences, Psychology, Mental Health, Tourette Syndrome, Neurosciences, Neurodegenerative, Pediatric, Clinical Research, Attention Deficit Hyperactivity Disorder (ADHD), Infant Mortality, Serious Mental Illness, Perinatal Period - Conditions Originating in Perinatal Period, Preterm, Low Birth Weight and Health of the Newborn, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Mental health, Good Health and Well Being, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Attention Deficit Disorder with Hyperactivity, Case-Control Studies, Child, Child, Preschool, Europe, Female, Humans, Male, Middle Aged, Obsessive-Compulsive Disorder, Parent-Child Relations, Pregnancy, Pregnancy Complications, Psychiatric Status Rating Scales, Republic of Korea, Retrospective Studies, Severity of Illness Index, Sex Factors, Tic Disorders, United States, Young Adult, Attention-deficit hyperactivity disorder, Delivery, Obsessive-compulsive disorder, Prenatal, Tourette syndrome, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Clinical sciences, Clinical and health psychology
Abstract

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD.

Published
2016

9. Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome

Author

Jain, Pritesh, Miller-Fleming, Tyne, Topaloudi, Apostolia, Yu, Dongmei, Drineas, Petros, Georgitsi, Marianthi, Yang, Zhiyu, Rizzo, Renata, Müller-Vahl, Kirsten R., Tumer, Zeynep, Mol Debes, Nanette, Hartmann, Andreas, Depienne, Christel, Worbe, Yulia, Mir, Pablo, Cath, Danielle C., Boomsma, Dorret I., Roessner, Veit, Wolanczyk, Tomasz, Janik, Piotr, Szejko, Natalia, Zekanowski, Cezary, Barta, Csaba, Nemoda, Zsofia, Tarnok, Zsanett, Buxbaum, Joseph D., Grice, Dorothy, Glennon, Jeffrey, Stefansson, Hreinn, Hengerer, Bastian, Benaroya-Milshtein, Noa, Cardona, Francesco, Hedderly, Tammy, Heyman, Isobel, Huyser, Chaim, Morer, Astrid, Mueller, Norbert, Munchau, Alexander, Plessen, Kerstin J., Porcelli, Cesare, Walitza, Susanne, Schrag, Anette, Martino, Davide, Dietrich, Andrea, Mathews, Carol A., Scharf, Jeremiah M., Hoekstra, Pieter J., Davis, Lea K., Paschou, Peristera, Als, Thomas D., Aschauer, Harald, Atzmon, Gil, Bækvad-Hansen, Matie, Barr, Cathy L., Barzilai, Nir, Batterson, James R., Batterson, Robert, Benarroch, Fortu, Berlin, Cheston, Boberg, Julia, Bodmer, Benjamin, Bohnenpoll, Julia, Børglum, Anders D., Brown, Lawrence W., Bruun, Ruth, Budman, Cathy L., Buckner, Randy L., Bybjerg-Grauholm, Jonas, Cheon, Keun-Ah, Chouinard, Sylvain, Coffey, Barbara J., Coppola, Giovanni, Crowley, James J., Dahl, Niklas, Darrow, Sabrina M., Daly, Mark J., De Rubeis, Silvia, Dion, Yves, Djurfeldt, Diana R., Domenech-Salgado, Laura, Eapen, Valsamma, Elzerman, Lonneke, Fernandez, Thomas V., Freimer Carolin Fremer, Nelson B., Garcia-Delgar, Blanca, Garrido, Marcos, Gilbert, Donald L., Giusti-Rodriguez, Paola, Grados, Marco, Greenberg, Erica, Grove, Jakob, Hagstrom, Julie, Halvorsen, Matt, Hansen, Bjarne, Haavik, Jan, Hebebrand, Johannes, Heiman, Gary A., Herrera, Luis, Hinney, Anke, Hirschtritt, Matthew E., Sul, Jae Hoon, Hong, Hyun Ju, Hougaard, David M., Huang, Alden Y., Ibanez-Gomez, Laura, Ivankovic, Franjo, Jankovic, Joseph, Karlsson, Elinor K., Kaprio, Jakko A., Kim, Young Key, Kim, Young-Shin, King, Robert A., Knowles, James A., Koh, Yun-Joo, Kook, Sodham, Khalifa, Najah, Konstantinidis, Anastasios, Kuperman, Samuel, Kurlan, Roger, Kvale, Gerd, Leckman, James, Lee, Paul C., Leventhal, Bennett, Lichtenstein, Paul, Lindbald-Toh, Kerstin, Lowe, Thomas, Ludolph, Andrea, da Silva, Claudia Luhrs, Luðvigsson, Pétur, Luykx, Jurjen, Lyon, Gholson J., Mahjani, Behrang, Maras, Athanasios, Mataix-Cols, David, Mattheisen, Manuel, Malaty, Irene A., McMahon, William M., McQuillin, Andrew, Meier, Sandra M., Moessner, Rainald, Mortensen, Preben B., Mors, Ole, Mudgal, Poorva, Nagy, Peter, Naarden, Allan, Neale, Benjamin M., Nawaz, Muhammad S., Nissen, Judith Becker, Nöthen Merete Nordentoft, Markus M., Nordsletten, Ashley E., Okun, Michael S., Ophoff, Roel, Osiecki, Lisa, Palotie, Aarno, Palviainen, Teemu P., Pato Michele T. Pato, Carlos N., Pittenger, Christopher, Pollak, Yehuda, Posthuma, Danielle, Ramos, Eliana, Reichert, Jennifer, Robertson, Mary M., Roffman, Joshua L., Rouleau, Guy, Rück, Christian, Sæmundsen, Evald, Samuels, Jack, Sandin, Sven, Sandor, Paul, Schlögelhofer, Monika, Shin, Eun-Young, Singer, Harvey S., Smit, Jan, Smoller, Jordan W., State, Matthew, Solem, Stian, Song, Dong-Ho, Song, Jungeun, Stamenkovic, Mara, Stefansson, Kári, Strom, Nora, Stuhrmann, Manfred, Szatkiewicz, Jin, Szymanska, Urszula, Tischfield, Jay A., Tsetsos, Fotis, Thorarensen, Ólafur, Tubing, Jennifer, Visscher, Frank, Wagner, Michael, Wanderer, Sina, Wang, Sheng, Werge, Thomas, Willsey, Jeremy A., Wolancyk, Tomasz, Woods, Douglas W., Woods, Martin, Zelaya, Ivette, Zinner, Samuel H., Apter, Alan, Ball, Juliane, Bognar, Emese, Buse, Judith, Vela, Marta Correa, Fremer, Carolin, 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, Fan, Siyan, Forde, Natalie J., Gerasch, Sarah, van den Heuvel, Odile A., Jespersgaard, Cathrine, Kanaan, Ahmad S., Möller, Harald E., 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., Biological Psychology, Amsterdam Reproduction & Development, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Dynamic Earth and Resources, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Medizin, Autism Spectrum Disorder/genetics, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Diabetes Mellitus, Type 2, Risk Factors, Diabetes Mellitus, Tourette Syndrome/genetics, Humans, Female, Attention Deficit Disorder with Hyperactivity/genetics, Type 2, Biological Psychiatry
Abstract

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders. Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.

Published
2023

10. Adverse events in cognitive behavioral therapy and relaxation training for children and adolescents with obsessive-compulsive disorder:A mixed methods study and analysis plan for the TECTO trial

Author

Pretzmann, Linea, Christensen, Sofie Heidenheim, Christensen, Anne Bryde, Funch Uhre, Camilla, Uhre, Valdemar, Thoustrup, Christine Lykke, Clemmesen, Iben Thiemer, Gudmandsen, Tin Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna Rosa Cecilie, Ritter, Melanie, Olsen, Markus Harboe, Clemmensen, Line Katrine Harder, Lindschou, Jane, Gluud, Christian, Thomsen, Per Hove, Vangkilde, Signe, Hagstrøm, Julie, Rozental, Alexander, Jeppesen, Pia, Verhulst, Frank, Hybel, Katja Anna, Lønfeldt, Nicole Nadine, Plessen, Kerstin Jessica, Poulsen, Stig, and Pagsberg, Anne Katrine

Subjects
Adolescent, Adverse effects, Obsessive-compulsive disorder, Randomized clinical trial, Child, Cognitive behavioral therapy
Abstract

Background: Knowledge on adverse events in psychotherapy for youth with OCD is sparse. No official guidelines exist for defining or monitoring adverse events in psychotherapy. Recent recommendations call for more qualitative and quantitative assessment of adverse events in psychotherapy trials. This mixed methods study aims to expand knowledge on adverse events in psychotherapy for youth with OCD. Methods: This is an analysis plan for a convergent mixed methods study within a randomized clinical trial (the TECTO trial). We include at least 128 youth aged 8–17 years with obsessive-compulsive disorder (OCD). Participants are randomized to either family-based cognitive behavioral therapy (FCBT) or family-based psychoeducation and relaxation training (FPRT). Adverse events are monitored quantitatively with the Negative Effects Questionnaire. Furthermore, we assess psychiatric symptoms, global functioning, quality of life, and family factors to investigate predictors for adverse events. We conduct semi-structured qualitative interviews with all youths and their parents on their experience of adverse events in FCBT or FPRT. For the mixed methods analysis, we will merge 1) a qualitative content analysis with descriptive statistics comparing the types, frequencies, and severity of adverse events; 2) a qualitative content analysis of the perceived causes for adverse events with prediction models for adverse events; and 3) a thematic analysis of the participants’ treatment evaluation with a correlational analysis of adverse events and OCD severity. Discussion: The in-depth mixed methods analysis can inform 1) safer and more effective psychotherapy for OCD; 2) instruments and guidelines for monitoring adverse events; and 3) patient information on potential adverse events. The main limitation is risk of missing data. Trial registration: ClinicalTrials.gov identifier: NCT03595098. Registered on July 23, 2018.

Published
2023

11. Correction:Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial) (BMC Psychiatry, (2022), 22, 1, (204), 10.1186/s12888-021-03669-2)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Abstract

Following publication of the original article [1], the authors identified an error in the author name of Line Katrine Harder Clemmensen. The incorrect author name is: Line Katrine Harder Clemmesen. The correct author name is: Line Katrine Harder Clemmensen. The author group has been updated above and the original article [1] has been corrected.

Published
2022

12. Associations Between the Severity of Obsessive-Compulsive Disorder and Vocal Features in Children and Adolescents: Protocol for a Statistical and Machine Learning Analysis

Author

Clemmensen, Line Katrine Harder, primary, Lønfeldt, Nicole Nadine, additional, Das, Sneha, additional, Lund, Nicklas Leander, additional, Uhre, Valdemar Funch, additional, Mora-Jensen, Anna-Rosa Cecilie, additional, Pretzmann, Linea, additional, Uhre, Camilla Funch, additional, Ritter, Melanie, additional, Korsbjerg, Nicoline Løcke Jepsen, additional, Hagstrøm, Julie, additional, Thoustrup, Christine Lykke, additional, Clemmesen, Iben Thiemer, additional, Plessen, Kersten Jessica, additional, and Pagsberg, Anne Katrine, additional

Published
2022
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13. Additional file 4 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Subjects
Data_FILES
Abstract

Additional file 4.

Published
2022
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14. Additional file 6 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Subjects
Data_FILES
Abstract

Additional file 6.

Published
2022
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15. Additional file 2 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Subjects
Data_FILES
Abstract

Additional file 2.

Published
2022
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16. Additional file 3 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Subjects
Data_FILES
Abstract

Additional file 3.

Published
2022
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17. Additional file 5 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents: protocol for a randomised clinical trial (the TECTO trial)

Author

Pagsberg, Anne Katrine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Clemmesen, Iben, Gudmandsen, Amanda Aaen, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Thorsen, Emilie D., Halberg, Klara Sofie Vangstrup, Bugge, Birgitte, Staal, Nina, Ingstrup, Helga Kristensen, Moltke, Birgitte Borgbjerg, Kloster, Anne Murphy, Zoega, Pernille Juul, Mikkelsen, Marie Sommer, Harboe, Gitte Sommer, Larsen, Katrin Frimann, Clemmensen, Line Katrine Harder, Lindschou, Jane, Jakobsen, Janus Christian, Engstrøm, Janus, Gluud, Christian, Siebner, Hartwig Roman, Thomsen, Per Hove, Hybel, Katja, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, and Plessen, Kerstin Jessica

Subjects
Data_FILES
Abstract

Additional file 5.

Published
2022
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18. Additional file 1 of Family-based cognitive behavioural therapy versus family-based relaxation therapy for obsessive-compulsive disorder in children and adolescents (the TECTO trial): a statistical analysis plan for the randomised clinical trial

Author

Olsen, Markus Harboe, Hagstrøm, Julie, Lønfeldt, Nicole Nadine, Uhre, Camilla, Uhre, Valdemar, Pretzmann, Linea, Christensen, Sofie Heidenheim, Thoustrup, Christine, Korsbjerg, Nicoline Løcke Jepsen, Mora-Jensen, Anna-Rosa Cecilie, Ritter, Melanie, Engstrøm, Janus, Lindschou, Jane, Siebner, Hartwig Roman, Verhulst, Frank, Jeppesen, Pia, Jepsen, Jens Richardt Møllegaard, Vangkilde, Signe, Thomsen, Per Hove, Hybel, Katja, Clemmesen, Line Katrine Harder, Gluud, Christian, Plessen, Kerstin Jessica, Pagsberg, Anne Katrine, and Jakobsen, Janus Christian

Abstract

Additional file 1: Table 1. Participant characteristics. Figure 1. CONSORT flow diagram. Figure 2. Psychopathology and family burden. Figure 3. Response status at 16 weeks. Figure 4. Negative effects questionnaire. Supplemental Table 1. Detailed comorbidities. Supplemental Table 2. Psychopathology and family burden. Supplemental Table 3. Kidscreen-52. Supplemental Timeline. Supplemental Assumptions.

Published
2022
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21. The Premonitory Urge for Tics Scale in a large sample of children and adolescents:psychometric properties in a developmental context. An EMTICS study

Author

Openneer, Thaïra J.C., Tárnok, Zsanett, Bognar, Emese, Benaroya-Milshtein, Noa, Garcia-Delgar, Blanca, Morer, Astrid, Steinberg, Tamar, Hoekstra, Pieter J., Dietrich, Andrea, Apter, Alan, Baglioni, Valentina, Ball, Juliane, Bodmer, Benjamin, Burger, Bianka, Buse, Judith, Cardona, Francesco, Correa Vela, Marta, Debes, Nanette M., Ferro, Maria Cristina, Fremer, Carolin, Gulisano, Mariangela, Hagen, Annelieke, Hagstrøm, Julie, Hedderly, Tammy J., Heyman, Isobel, Huyser, Chaim, Madruga-Garrido, Marcos, Marotta, Anna, Mir, Pablo, Müller, Norbert, Müller-Vahl, Kirsten, Münchau, Alexander, Nagy, Peter, Neri, Valeria, Pellico, Alessandra, Plessen, Kerstin J., Porcelli, Cesare, Redondo, Marina, Rizzo, Renata, Roessner, Veit, Ruhrman, Daphna, Schnell, Jaana M.L., Silvestri, Paola Rosaria, Skov, Liselotte, Tagwerker Gloor, Friederike, Tübing, Jennifer, Turner, Victoria L., Visscher, Frank, and the EMTICS collaborative group, Apter, A., Baglioni, V., Ball, J., Benaroya-Milshtein, N., Bodmer, B., Bognar, E., Burger, B., Buse, J., Cardona, F., Correa Vela, M., Debes, N.M., Dietrich, A., Ferro, M.C., Fremer, C., Garcia-Delgar, B., Gulisano, M., Hagen, A., Hagstrøm, J., Hedderly, T.J., Heyman, I., Hoekstra, P.J., Huyser, C., Madruga-Garrido, M., Marotta, A., Mir, P., Morer, A., Müller, N., Müller-Vahl, K., Münchau, A., Nagy, P., Neri, V., Openneer, TJC, Pellico, A., Plessen, K.J., Porcelli, C., Redondo, M., Rizzo, R., Roessner, V., Ruhrman, D., Schnell, JML, Silvestri, P.R., Skov, L., Steinberg, T., Tagwerker Gloor, F., Tárnok, Z., Tübing, J., Turner, V.L., Visscher, F., ANS - Cellular & Molecular Mechanisms, Child Psychiatry, ANS - Amsterdam Neuroscience, and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Sensory phenomena, Male, Tourette syndrome, THERAPY, Severity of Illness Index, Obsessive-compulsive symptoms, 0302 clinical medicine, Quality of life, QUALITY-OF-LIFE, Developmental and Educational Psychology, Child and adolescent psychiatry, 030212 general & internal medicine, ADULT PATIENTS, Child, Premonitory Urge for Tics Scale (PUTS), Obsessive–compulsive symptoms, Premonitory urges, Psychometric properties, General Medicine, Original Contribution, Psychiatry and Mental health, Child, Preschool, Female, medicine.symptom, Psychology, Clinical psychology, medicine.medical_specialty, Tics, Adolescent, Psychometrics, DISORDERS, QUESTIONNAIRE, Context (language use), 03 medical and health sciences, OBSESSIVE-COMPULSIVE SCALE, medicine, SENSORY PHENOMENA, Humans, TOURETTE-SYNDROME, HABIT REVERSAL, Reproducibility of Results, medicine.disease, SEVERITY, Sample size determination, Tic Disorders, Pediatrics, Perinatology and Child Health, Chronic Tic Disorder, 030217 neurology & neurosurgery
Abstract

Premonitory urges are uncomfortable physical sensations preceding tics that occur in most individuals with a chronic tic disorder. The Premonitory Urge for Tics Scale (PUTS) is the most frequently used self-report measure to assess the severity of premonitory urges. We aimed to evaluate the psychometric properties of the PUTS in the largest sample size to date (n = 656), in children aged 3–16 years, from the baseline measurement of the longitudinal European Multicenter Tics in Children Study (EMTICS). Our psychometric evaluation was done in three age-groups: children aged 3–7 years (n = 103), children between 8 and 10 years (n = 253), and children aged 11–16 years (n = 300). The PUTS exhibited good internal reliability in children and adolescents, also under the age of 10, which is younger than previously thought. We observed significant but small correlations between the severity of urges and severity of tics and obsessive–compulsive symptoms, and between severity of urges and ratings of attention-deficit/hyperactivity disorder and internalizing and externalizing behaviors, however, only in children of 8–10 years. Consistent with previous results, the 10th item of the PUTS correlated less with the rest of the scale compared to the other items and, therefore, should not be used as part of the questionnaire. We found a two-factor structure of the PUTS in children of 11 years and older, distinguishing between sensory phenomena related to tics, and mental phenomena as often found in obsessive–compulsive disorder. The age-related differences observed in this study may indicate the need for the development of an age-specific questionnaire to assess premonitory urges. Electronic supplementary material The online version of this article (10.1007/s00787-019-01450-1) contains supplementary material, which is available to authorized users.

Published
2020

22. Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

Author

Lee, Phil H., primary, Anttila, Verneri, additional, Won, Hyejung, additional, Feng, Yen-Chen A., additional, Rosenthal, Jacob, additional, Zhu, Zhaozhong, additional, Tucker-Drob, Elliot M., additional, Nivard, Michel G., additional, Grotzinger, Andrew D., additional, Posthuma, Danielle, additional, Wang, Meg M.-J., additional, Yu, Dongmei, additional, Stahl, Eli A., additional, Walters, Raymond K., additional, Anney, Richard J.L., additional, Duncan, Laramie E., additional, Ge, Tian, additional, Adolfsson, Rolf, additional, Banaschewski, Tobias, additional, Belangero, Sintia, additional, Cook, Edwin H., additional, Coppola, Giovanni, additional, Derks, Eske M., additional, Hoekstra, Pieter J., additional, Kaprio, Jaakko, additional, Keski-Rahkonen, Anna, additional, Kirov, George, additional, Kranzler, Henry R., additional, Luykx, Jurjen J., additional, Rohde, Luis A., additional, Zai, Clement C., additional, Agerbo, Esben, additional, Arranz, M.J., additional, Asherson, Philip, additional, Bækvad-Hansen, Marie, additional, Baldursson, Gísli, additional, Bellgrove, Mark, additional, Belliveau, Richard A., additional, Buitelaar, Jan, additional, Burton, Christie L., additional, Bybjerg-Grauholm, Jonas, additional, Casas, Miquel, additional, Cerrato, Felecia, additional, Chambert, Kimberly, additional, Churchhouse, Claire, additional, Cormand, Bru, additional, Crosbie, Jennifer, additional, Dalsgaard, Søren, additional, Demontis, Ditte, additional, Doyle, Alysa E., additional, Dumont, Ashley, additional, Elia, Josephine, additional, Grove, Jakob, additional, Gudmundsson, Olafur O., additional, Haavik, Jan, additional, Hakonarson, Hakon, additional, Hansen, Christine S., additional, Hartman, Catharina A., additional, Hawi, Ziarih, additional, Hervás, Amaia, additional, Hougaard, David M., additional, Howrigan, Daniel P., additional, Huang, Hailiang, additional, Kuntsi, Jonna, additional, Langley, Kate, additional, Lesch, Klaus-Peter, additional, Leung, Patrick W.L., additional, Loo, Sandra K., additional, Martin, Joanna, additional, Martin, Alicia R., additional, McGough, James J., additional, Medland, Sarah E., additional, Moran, Jennifer L., additional, Mors, Ole, additional, Mortensen, Preben B., additional, Oades, Robert D., additional, Palmer, Duncan S., additional, Pedersen, Carsten B., additional, Pedersen, Marianne G., additional, Peters, Triinu, additional, Poterba, Timothy, additional, Poulsen, Jesper B., additional, Ramos-Quiroga, Josep Antoni, additional, Reif, Andreas, additional, Ribasés, Marta, additional, Rothenberger, Aribert, additional, Rovira, Paula, additional, Sánchez-Mora, Cristina, additional, Satterstrom, F. Kyle, additional, Schachar, Russell, additional, Artigas, Maria Soler, additional, Steinberg, Stacy, additional, Stefansson, Hreinn, additional, Turley, Patrick, additional, Walters, G. Bragi, additional, Werge, Thomas, additional, Zayats, Tetyana, additional, Arking, Dan E., additional, Bettella, Francesco, additional, Buxbaum, Joseph D., additional, Christensen, Jane H., additional, Collins, Ryan L., additional, Coon, Hilary, additional, De Rubeis, Silvia, additional, Delorme, Richard, additional, Grice, Dorothy E., additional, Hansen, Thomas F., additional, Holmans, Peter A., additional, Hope, Sigrun, additional, Hultman, Christina M., additional, Klei, Lambertus, additional, Ladd-Acosta, Christine, additional, Magnusson, Pall, additional, Nærland, Terje, additional, Nyegaard, Mette, additional, Pinto, Dalila, additional, Qvist, Per, additional, Rehnström, Karola, additional, Reichenberg, Abraham, additional, Reichert, Jennifer, additional, Roeder, Kathryn, additional, Rouleau, Guy A., additional, Saemundsen, Evald, additional, Sanders, Stephan J., additional, Sandin, Sven, additional, St Pourcain, Beate, additional, Stefansson, Kari, additional, Sutcliffe, James S., additional, Talkowski, Michael E., additional, Weiss, Lauren A., additional, Willsey, A. Jeremy, additional, Agartz, Ingrid, additional, Akil, Huda, additional, Albani, Diego, additional, Alda, Martin, additional, Als, Thomas D., additional, Anjorin, Adebayo, additional, Backlund, Lena, additional, Bass, Nicholas, additional, Bauer, Michael, additional, Baune, Bernhard T., additional, Bellivier, Frank, additional, Bergen, Sarah E., additional, Berrettini, Wade H., additional, Biernacka, Joanna M., additional, Blackwood, Douglas H.R., additional, Bøen, Erlend, additional, Budde, Monika, additional, Bunney, William, additional, Burmeister, Margit, additional, Byerley, William, additional, Byrne, Enda M., additional, Cichon, Sven, additional, Clarke, Toni-Kim, additional, Coleman, Jonathan R.I., additional, Craddock, Nicholas, additional, Curtis, David, additional, Czerski, Piotr M., additional, Dale, Anders M., additional, Dalkner, Nina, additional, Dannlowski, Udo, additional, Degenhardt, Franziska, additional, Di Florio, Arianna, additional, Elvsåshagen, Torbjørn, additional, Etain, Bruno, additional, Fischer, Sascha B., additional, Forstner, Andreas J., additional, Forty, Liz, additional, Frank, Josef, additional, Frye, Mark, additional, Fullerton, Janice M., additional, Gade, Katrin, additional, Gaspar, Héléna A., additional, Gershon, Elliot S., additional, Gill, Michael, additional, Goes, Fernando S., additional, Gordon, Scott D., additional, Gordon-Smith, Katherine, additional, Green, Melissa J., additional, Greenwood, Tiffany A., additional, Grigoroiu-Serbanescu, Maria, additional, Guzman-Parra, José, additional, Hauser, Joanna, additional, Hautzinger, Martin, additional, Heilbronner, Urs, additional, Herms, Stefan, additional, Hoffmann, Per, additional, Holland, Dominic, additional, Jamain, Stéphane, additional, Jones, Ian, additional, Jones, Lisa A., additional, Kandaswamy, Radhika, additional, Kelsoe, John R., additional, Kennedy, James L., additional, Joachim, Oedegaard Ketil, additional, Kittel-Schneider, Sarah, additional, Kogevinas, Manolis, additional, Koller, Anna C., additional, Lavebratt, Catharina, additional, Lewis, Cathryn M., additional, Li, Qingqin S., additional, Lissowska, Jolanta, additional, Loohuis, Loes M.O., additional, Lucae, Susanne, additional, Maaser, Anna, additional, Malt, Ulrik F., additional, Martin, Nicholas G., additional, Martinsson, Lina, additional, McElroy, Susan L., additional, McMahon, Francis J., additional, McQuillin, Andrew, additional, Melle, Ingrid, additional, Metspalu, Andres, additional, Millischer, Vincent, additional, Mitchell, Philip B., additional, Montgomery, Grant W., additional, Morken, Gunnar, additional, Morris, Derek W., additional, Müller-Myhsok, Bertram, additional, Mullins, Niamh, additional, Myers, Richard M., additional, Nievergelt, Caroline M., additional, Nordentoft, Merete, additional, Adolfsson, Annelie Nordin, additional, Nöthen, Markus M., additional, Ophoff, Roel A., additional, Owen, Michael J., additional, Paciga, Sara A., additional, Pato, Carlos N., additional, Pato, Michele T., additional, Perlis, Roy H., additional, Perry, Amy, additional, Potash, James B., additional, Reinbold, Céline S., additional, Rietschel, Marcella, additional, Rivera, Margarita, additional, Roberson, Mary, additional, Schalling, Martin, additional, Schofield, Peter R., additional, Schulze, Thomas G., additional, Scott, Laura J., additional, Serretti, Alessandro, additional, Sigurdsson, Engilbert, additional, Smeland, Olav B., additional, Stordal, Eystein, additional, Streit, Fabian, additional, Strohmaier, Jana, additional, Thorgeirsson, Thorgeir E., additional, Treutlein, Jens, additional, Turecki, Gustavo, additional, Vaaler, Arne E., additional, Vieta, Eduard, additional, Vincent, John B., additional, Wang, Yunpeng, additional, Witt, Stephanie H., additional, Zandi, Peter, additional, Adan, Roger A.H., additional, Alfredsson, Lars, additional, Ando, Tetsuya, additional, Aschauer, Harald, additional, Baker, Jessica H., additional, Bencko, Vladimir, additional, Bergen, Andrew W., additional, Birgegård, Andreas, additional, Perica, Vesna Boraska, additional, Brandt, Harry, additional, Burghardt, Roland, additional, Carlberg, Laura, additional, Cassina, Matteo, additional, Clementi, Maurizio, additional, Courtet, Philippe, additional, Crawford, Steven, additional, Crow, Scott, additional, Crowley, James J., additional, Danner, Unna N., additional, Davis, Oliver S.P., additional, Degortes, Daniela, additional, DeSocio, Janiece E., additional, Dick, Danielle M., additional, Dina, Christian, additional, Docampo, Elisa, additional, Egberts, Karin, additional, Ehrlich, Stefan, additional, Espeseth, Thomas, additional, Fernández-Aranda, Fernando, additional, Fichter, Manfred M., additional, Foretova, Lenka, additional, Forzan, Monica, additional, Gambaro, Giovanni, additional, Giegling, Ina, additional, Gonidakis, Fragiskos, additional, Gorwood, Philip, additional, Mayora, Monica Gratacos, additional, Guo, Yiran, additional, Halmi, Katherine A., additional, Hatzikotoulas, Konstantinos, additional, Hebebrand, Johannes, additional, Helder, Sietske G., additional, Herpertz-Dahlmann, Beate, additional, Herzog, Wolfgang, additional, Hinney, Anke, additional, Imgart, Hartmut, additional, Jiménez-Murcia, Susana, additional, Johnson, Craig, additional, Jordan, Jennifer, additional, Julià, Antonio, additional, Kaminská, Deborah, additional, Karhunen, Leila, additional, Karwautz, Andreas, additional, Kas, Martien J.H., additional, Kaye, Walter H., additional, Kennedy, Martin A., additional, Kim, Youl-Ri, additional, Klareskog, Lars, additional, Klump, Kelly L., additional, Knudsen, Gun Peggy S., additional, Landén, Mikael, additional, Le Hellard, Stephanie, additional, Levitan, Robert D., additional, Li, Dong, additional, Lichtenstein, Paul, additional, Maj, Mario, additional, Marsal, Sara, additional, McDevitt, Sara, additional, Mitchell, James, additional, Monteleone, Palmiero, additional, Monteleone, Alessio Maria, additional, Munn-Chernoff, Melissa A., additional, Nacmias, Benedetta, additional, Navratilova, Marie, additional, O’Toole, Julie K., additional, Padyukov, Leonid, additional, Pantel, Jacques, additional, Papezova, Hana, additional, Rabionet, Raquel, additional, Raevuori, Anu, additional, Ramoz, Nicolas, additional, Reichborn-Kjennerud, Ted, additional, Ricca, Valdo, additional, Roberts, Marion, additional, Rujescu, Dan, additional, Rybakowski, Filip, additional, Scherag, André, additional, Schmidt, Ulrike, additional, Seitz, Jochen, additional, Slachtova, Lenka, additional, Slof-Op‘t Landt, Margarita C.T., additional, Slopien, Agnieszka, additional, Sorbi, Sandro, additional, Southam, Lorraine, additional, Strober, Michael, additional, Tortorella, Alfonso, additional, Tozzi, Federica, additional, Treasure, Janet, additional, Tziouvas, Konstantinos, additional, van Elburg, Annemarie A., additional, Wade, Tracey D., additional, Wagner, Gudrun, additional, Walton, Esther, additional, Watson, Hunna J., additional, Wichmann, H-Erich, additional, Woodside, D. Blake, additional, Zeggini, Eleftheria, additional, Zerwas, Stephanie, additional, Zipfel, Stephan, additional, Adams, Mark J., additional, Andlauer, Till F.M., additional, Berger, Klaus, additional, Binder, Elisabeth B., additional, Boomsma, Dorret I., additional, Castelao, Enrique, additional, Colodro-Conde, Lucía, additional, Direk, Nese, additional, Docherty, Anna R., additional, Domenici, Enrico, additional, Domschke, Katharina, additional, Dunn, Erin C., additional, Foo, Jerome C., additional, de. Geus, E.J.C., additional, Grabe, Hans J., additional, Hamilton, Steven P., additional, Horn, Carsten, additional, Hottenga, Jouke-Jan, additional, Howard, David, additional, Ising, Marcus, additional, Kloiber, Stefan, additional, Levinson, Douglas F., additional, Lewis, Glyn, additional, Magnusson, Patrik K.E., additional, Mbarek, Hamdi, additional, Middeldorp, Christel M., additional, Mostafavi, Sara, additional, Nyholt, Dale R., additional, Penninx, Brenda WJH., additional, Peterson, Roseann E., additional, Pistis, Giorgio, additional, Porteous, David J., additional, Preisig, Martin, additional, Quiroz, Jorge A., additional, Schaefer, Catherine, additional, Schulte, Eva C., additional, Shi, Jianxin, additional, Smith, Daniel J., additional, Thomson, Pippa A., additional, Tiemeier, Henning, additional, Uher, Rudolf, additional, van der Auwera, Sandra, additional, Weissman, Myrna M., additional, Alexander, Madeline, additional, Begemann, Martin, additional, Bramon, Elvira, additional, Buccola, Nancy G., additional, Cairns, Murray J., additional, Campion, Dominique, additional, Carr, Vaughan J., additional, Cloninger, C. Robert, additional, Cohen, David, additional, Collier, David A., additional, Corvin, Aiden, additional, DeLisi, Lynn E., additional, Donohoe, Gary, additional, Dudbridge, Frank, additional, Duan, Jubao, additional, Freedman, Robert, additional, Gejman, Pablo V., additional, Golimbet, Vera, additional, Godard, Stephanie, additional, Ehrenreich, Hannelore, additional, Hartmann, Annette M., additional, Henskens, Frans A., additional, Ikeda, Masashi, additional, Iwata, Nakao, additional, Jablensky, Assen V., additional, Joa, Inge, additional, Jönsson, Erik G., additional, Kelly, Brian J., additional, Knight, Jo, additional, Konte, Bettina, additional, Laurent-Levinson, Claudine, additional, Lee, Jimmy, additional, Lencz, Todd, additional, Lerer, Bernard, additional, Loughland, Carmel M., additional, Malhotra, Anil K., additional, Mallet, Jacques, additional, McDonald, Colm, additional, Mitjans, Marina, additional, Mowry, Bryan J., additional, Murphy, Kieran C., additional, Murray, Robin M., additional, O’Neill, F. Anthony, additional, Oh, Sang-Yun, additional, Palotie, Aarno, additional, Pantelis, Christos, additional, Pulver, Ann E., additional, Petryshen, Tracey L., additional, Quested, Digby J., additional, Riley, Brien, additional, Sanders, Alan R., additional, Schall, Ulrich, additional, Schwab, Sibylle G., additional, Scott, Rodney J., additional, Sham, Pak C., additional, Silverman, Jeremy M., additional, Sim, Kang, additional, Steixner, Agnes A., additional, Tooney, Paul A., additional, van Os, Jim, additional, Vawter, Marquis P., additional, Walsh, Dermot, additional, Weiser, Mark, additional, Wildenauer, Dieter B., additional, Williams, Nigel M., additional, Wormley, Brandon K., additional, Zhang, Fuquan, additional, Androutsos, Christos, additional, Arnold, Paul D., additional, Barr, Cathy L., additional, Barta, Csaba, additional, Bey, Katharina, additional, Bienvenu, O. Joseph, additional, Black, Donald W., additional, Brown, Lawrence W., additional, Budman, Cathy, additional, Cath, Danielle, additional, Cheon, Keun-Ah, additional, Ciullo, Valentina, additional, Coffey, Barbara J., additional, Cusi, Daniele, additional, Davis, Lea K., additional, Denys, Damiaan, additional, Depienne, Christel, additional, Dietrich, Andrea, additional, Eapen, Valsamma, additional, Falkai, Peter, additional, Fernandez, Thomas V., additional, Garcia-Delgar, Blanca, additional, Geller, Daniel A., additional, Gilbert, Donald L., additional, Grados, Marco A., additional, Greenberg, Erica, additional, Grünblatt, Edna, additional, Hagstrøm, Julie, additional, Hanna, Gregory L., additional, Hartmann, Andreas, additional, Hedderly, Tammy, additional, Heiman, Gary A., additional, Heyman, Isobel, additional, Hong, Hyun Ju, additional, Huang, Alden, additional, Huyser, Chaim, additional, Ibanez-Gomez, Laura, additional, Khramtsova, Ekaterina A., additional, Kim, Young Key, additional, Kim, Young-Shin, additional, King, Robert A., additional, Koh, Yun-Joo, additional, Konstantinidis, Anastasios, additional, Kook, Sodahm, additional, Kuperman, Samuel, additional, Leventhal, Bennett L., additional, Lochner, Christine, additional, Ludolph, Andrea G., additional, Madruga-Garrido, Marcos, additional, Malaty, Irene, additional, Maras, Athanasios, additional, McCracken, James T., additional, Meijer, Inge A., additional, Mir, Pablo, additional, Morer, Astrid, additional, Müller-Vahl, Kirsten R., additional, Münchau, Alexander, additional, Murphy, Tara L., additional, Naarden, Allan, additional, Nagy, Peter, additional, Nestadt, Gerald, additional, Nestadt, Paul S., additional, Nicolini, Humberto, additional, Nurmi, Erika L., additional, Okun, Michael S., additional, Paschou, Peristera, additional, Piras, Fabrizio, additional, Piras, Federica, additional, Pittenger, Christopher, additional, Plessen, Kerstin J., additional, Richter, Margaret A., additional, Rizzo, Renata, additional, Robertson, Mary, additional, Roessner, Veit, additional, Ruhrmann, Stephan, additional, Samuels, Jack F., additional, Sandor, Paul, additional, Schlögelhofer, Monika, additional, Shin, Eun-Young, additional, Singer, Harvey, additional, Song, Dong-Ho, additional, Song, Jungeun, additional, Spalletta, Gianfranco, additional, Stein, Dan J., additional, Stewart, S Evelyn, additional, Storch, Eric A., additional, Stranger, Barbara, additional, Stuhrmann, Manfred, additional, Tarnok, Zsanett, additional, Tischfield, Jay A., additional, Tübing, Jennifer, additional, Visscher, Frank, additional, Vulink, Nienke, additional, Wagner, Michael, additional, Walitza, Susanne, additional, Wanderer, Sina, additional, Woods, Martin, additional, Worbe, Yulia, additional, Zai, Gwyneth, additional, Zinner, Samuel H., additional, Sullivan, Patrick F., additional, Franke, Barbara, additional, Daly, Mark J., additional, Bulik, Cynthia M., additional, McIntosh, Andrew M., additional, O’Donovan, Michael C., additional, Zheutlin, Amanda, additional, Andreassen, Ole A., additional, Børglum, Anders D., additional, Breen, Gerome, additional, Edenberg, Howard J., additional, Fanous, Ayman H., additional, Faraone, Stephen V., additional, Gelernter, Joel, additional, Mathews, Carol A., additional, Mattheisen, Manuel, additional, Mitchell, Karen S., additional, Neale, Michael C., additional, Nurnberger, John I., additional, Ripke, Stephan, additional, Santangelo, Susan L., additional, Scharf, Jeremiah M., additional, Stein, Murray B., additional, Thornton, Laura M., additional, Walters, James T.R., additional, Wray, Naomi R., additional, Geschwind, Daniel H., additional, Neale, Benjamin M., additional, Kendler, Kenneth S., additional, and Smoller, Jordan W., additional

Published
2019
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24. 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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25. 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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26. 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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27. Synaptic processes and immune-related pathways implicated in Tourette syndrome.

Author

Tsetsos F, Yu D, Sul JH, Huang AY, Illmann C, Osiecki L, Darrow SM, Hirschtritt ME, Greenberg E, Muller-Vahl KR, Stuhrmann M, Dion Y, Rouleau GA, Aschauer H, Stamenkovic M, Schlögelhofer M, Sandor P, Barr CL, Grados MA, Singer HS, Nöthen MM, Hebebrand J, Hinney A, King RA, Fernandez TV, Barta C, Tarnok Z, Nagy P, Depienne C, Worbe Y, Hartmann A, Budman CL, Rizzo R, Lyon GJ, McMahon WM, Batterson JR, Cath DC, Malaty IA, Okun MS, Berlin C, Woods DW, Lee PC, Jankovic J, Robertson MM, Gilbert DL, Brown LW, Coffey BJ, Dietrich A, Hoekstra PJ, Kuperman S, Zinner SH, Wagner M, Knowles JA, Jeremy Willsey A, Tischfield JA, Heiman GA, Cox NJ, Freimer NB, Neale BM, Davis LK, Coppola G, Mathews CA, Scharf JM, Paschou P, Barr CL, Batterson JR, Berlin C, Budman CL, Cath DC, Coppola G, Cox NJ, Darrow S, Davis LK, Dion Y, Freimer NB, Grados MA, Greenberg E, Hirschtritt ME, Huang AY, Illmann C, King RA, Kurlan R, Leckman JF, Lyon GJ, Malaty IA, Mathews CA, McMahon WM, Neale BM, Okun MS, Osiecki L, Robertson MM, Rouleau GA, Sandor P, Scharf JM, Singer HS, Smit JH, Sul JH, Yu D, Aschauer HAH, Barta C, Budman CL, Cath DC, Depienne C, Hartmann A, Hebebrand J, Konstantinidis A, Mathews CA, Müller-Vahl K, Nagy P, Nöthen MM, Paschou P, Rizzo R, Rouleau GA, Sandor P, Scharf JM, Schlögelhofer M, Stamenkovic M, Stuhrmann M, Tsetsos F, Tarnok Z, Wolanczyk T, Worbe Y, Brown L, Cheon KA, Coffey BJ, Dietrich A, Fernandez TV, Garcia-Delgar B, Gilbert D, Grice DE, Hagstrøm J, Hedderly T, Heiman GA, Heyman I, Hoekstra PJ, Huyser C, Kim YK, Kim YS, King RA, Koh YJ, Kook S, Kuperman S, Leventhal BL, Madruga-Garrido M, Mir P, Morer A, Münchau A, Plessen KJ, Roessner V, Shin EY, Song DH, Song J, Tischfield JA, Willsey AJ, Zinner S, Aschauer H, Barr CL, Barta C, Batterson JR, Berlin C, Brown L, Budman CL, Cath DC, Coffey BJ, Coppola G, Cox NJ, Darrow S, Davis LK, Depienne C, Dietrich A, Dion Y, Fernandez T, Freimer NB, Gilbert D, Grados MA, Greenberg E, Hartmann A, Hebebrand J, Heiman G, Hirschtritt ME, Hoekstra P, Huang AY, Illmann C, Jankovic J, King RA, Kuperman S, Lee PC, Lyon GJ, Malaty IA, Mathews CA, McMahon WM, Müller-Vahl K, Nagy P, Neale BM, Nöthen MM, Okun MS, Osiecki L, Paschou P, Rizzo R, Robertson MM, Rouleau GA, Sandor P, Scharf JM, Schlögelhofer M, Singer HS, Stamenkovic M, Stuhrmann M, Sul JH, Tarnok Z, Tischfield J, Tsetsos F, Willsey AJ, Woods D, Worbe Y, Yu D, and Zinner S

Subjects
Genome-Wide Association Study, Genotype, Humans, Neurons, Tourette Syndrome genetics
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
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