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11,157 results on '"King, Robert"'

51. Awake intracerebroventricular delivery and safety assessment of oligonucleotides in a large animal model

Author

Benatti, Hector Ribeiro, Prestigiacomo, Rachel D., Taghian, Toloo, Miller, Rachael, King, Robert, Gounis, Matthew J., Celik, Ugur, Bertrand, Stephanie, Tuominen, Susan, Bierfeldt, Lindsey, Parsley, Elizabeth, Gallagher, Jillian, Hall, Erin F., McElroy, Abigail W., Sena-Esteves, Miguel, Khvorova, Anastasia, Aronin, Neil, and Gray-Edwards, Heather L.

Published
2023
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55. 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

58. Assessment of thrombectomy procedure difficulty by neurointerventionalists based on vessel geometry parameters from carotid artery 3D reconstructions

Author

Shazeeb, Mohammed Salman, Moholkar, Viraj, King, Robert M., Vedantham, Srinivasan, Vardar, Zeynep, Kraitem, Afif, Lindsay, Clifford, Anagnostakou, Vania, Singh, Jasmeet, Massari, Francesco, de Macedo Rodrigues, Katyucia, Naragum, Varun, Puri, Ajit S., Carniato, Sarena, Gounis, Matthew J., and Kühn, Anna Luisa

Published
2023
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64. Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe

Author

Pereira, Vitor M., primary, Lylyk, Pedro, additional, Cancelliere, Nicole, additional, Lylyk, Pedro N., additional, Lylyk, Ivan, additional, Anagnostakou, Vania, additional, Bleise, Carlos, additional, Nishi, Hidehisa, additional, Epshtein, Mark, additional, King, Robert M., additional, Shazeeb, Mohammed Salman, additional, Puri, Ajit S., additional, Liang, Conrad W., additional, Hanel, Ricardo A., additional, Spears, Julian, additional, Marotta, Thomas R., additional, Lopes, Demetrius K., additional, Gounis, Matthew J., additional, and Ughi, Giovanni J., additional

Published
2024
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66. 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

68. THE DEPICTION OF THE OCEAN ON THE 1519 WORLD MAP OF LOPO HOMEM

Author

King, Robert J.

Subjects
Ocean, Geography, Library and information science
Abstract

The map of the world made by Lopo Homem in 1519 depicts the world Ocean, under the names OCCEANUS meridionals and indicummare, enclosed by the three classical continents, Europe, Asia and Africa, and the New World including the austral TERRA INCOGNITA. This configuration was apparently drawn from the description of the world given by Duarte Pacheco Pereira in 1508 and set out in his since lost map. Other world maps of this type are that shown on the 1525 tapestry by Bernaert van Orley and Georg Wezeler, and on the 1513 world map of Pin Reis. It is argued here that Homem's map represented a stage in cartographical history when Ptolemy's enclosed Indian Ocean was enlarged to become an enclosed world Ocean until, following Magellan's expedition, it was recognized that the Ocean was much larger than the authority of the Biblical Fourth Book of Esdras had ascribed to it, and that indeed it did surround the continental parts of the Earth., The 1519 world map by the Portuguese cartographer and cosmographer Lopo Homem, Universi Orbis adhanc usqe diem cogniti Tabula (Map of the Whole World as known to this day) (Fig- [...]

Published
2022

71. Deciphering climate-induced displacement in Somalia: A remote sensing perspective.

Author

Momeni, Rahman, Bircan, Tuba, King, Robert, and Santos, Eloy Zafra

Subjects
EXTREME weather, DATA analytics, REMOTE sensing, SOCIOECONOMIC factors, INTERNALLY displaced persons
Abstract

Rapid climate changes bear significant consequences on various aspects of our lives, notably by deteriorating living conditions in certain areas to such extent that inhabitants have no choice but flee. Despite recognition of this issue, the dynamics of the relationship between the environmental factors and the human mobility have yet to be thoroughly investigated. This study aims to explore the application of advanced remote sensing analytics for developing detailed climate indicators at a micro (district) level, and to examine the relationship between climate factors and internally displaced persons. After detailing our data sources and the analytics employed for indicator development, we discuss various types of events and their repercussions. Our findings corroborate that slow-onset and rapid-onset climate events differently impact society, and the responses hinge on the urgency precipitated by the detrimental aftermath of the extreme weather event and, most crucially, on people's capabilities. We also underscore the importance of data quality and availability for the socio-economic indicators to enhance future studies, given the intertwined associations between climate change, economic deprivation, and violent conflict. [ABSTRACT FROM AUTHOR]

Published
2024
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72. Knotted fields and explicit fibrations for lemniscate knots

Author

Bode, Benjamin, Dennis, Mark R, Foster, David, and King, Robert P

Subjects
Mathematics - Geometric Topology, Mathematical Physics
Abstract

We give an explicit construction of complex maps whose nodal line have the form of lemniscate knots. We review the properties of lemniscate knots, defined as closures of braids where all strands follow the same transverse (1, $\ell$) Lissajous figure, and are therefore a subfamily of spiral knots generalising the torus knots. We then prove that such maps exist and are in fact fibrations with appropriate choices of parameters. We describe how this may be useful in physics for creating knotted fields, in quantum mechanics, optics and generalising to rational maps with application to the Skyrme-Faddeev model. We also prove how this construction extends to maps with weakly isolated singularities., Comment: 20 pages, 8 figures

Published
2016
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75. Psychological Determinism

Author

King, Robert, Appleby, Marcus, Kamble, Shanmukh, Section editor, Shackelford, Todd K, editor, and Weekes-Shackelford, Viviana A, editor

Published
2021
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76. Randy Thornhill

Author

King, Robert, Brewer, Gayle, Section editor, Shackelford, Todd K, editor, and Weekes-Shackelford, Viviana A, editor

Published
2021
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78. Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide

Author

Tran, Hélène, Moazami, Michael P., Yang, Huiya, McKenna-Yasek, Diane, Douthwright, Catherine L., Pinto, Courtney, Metterville, Jake, Shin, Minwook, Sanil, Nitasha, Dooley, Craig, Puri, Ajit, Weiss, Alexandra, Wightman, Nicholas, Gray-Edwards, Heather, Marosfoi, Miklos, King, Robert M., Kenderdine, Thomas, Fabris, Daniele, Bowser, Robert, Watts, Jonathan K., and Brown, Jr, Robert H.

Published
2022
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79. De Novo Sequence 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, Tourette International Collaborative Genetics Study (TIC Genetics), Tourette Syndrome Genetics Southern and Eastern Europe Initiative (TSGENESEE), Tourette Association of America International Consortium for Genetics (TAAICG), 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

Subjects
Tourette International Collaborative Genetics Study, Tourette Syndrome Genetics Southern and Eastern Europe Initiative, Tourette Association of America International Consortium for Genetics, Humans, Tourette Syndrome, Cadherins, Receptors, Cell Surface, Pedigree, Cell Polarity, Adult, Child, Female, Male, DNA Copy Number Variations, TIC Genetics, Tourette disorder, cell polarity, copy number variants, de novo variants, gene discovery, microarray genotyping, multiplex, simplex, whole exome sequencing, Clinical Research, Pediatric, Biotechnology, Genetics, Brain Disorders, Human Genome, Intellectual and Developmental Disabilities (IDD), Neurodegenerative, 2.1 Biological and endogenous factors, Aetiology, Biochemistry and Cell Biology, Medical Physiology
Abstract

We previously established the contribution of de novo damaging 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 novo damaging 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 novo copy number variants in TD. Finally, we identify significant overlap of de novo sequence variants between TD and obsessive-compulsive disorder and de novo copy number variants between TD and autism spectrum disorder, consistent with shared genetic risk.

Published
2018

80. 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

81. Investigation of previously implicated genetic variants in chronic tic disorders: a transmission disequilibrium test approach

Author

Abdulkadir, Mohamed, Londono, Douglas, Gordon, Derek, Fernandez, Thomas V, Brown, Lawrence W, Cheon, Keun-Ah, Coffey, Barbara J, Elzerman, Lonneke, Fremer, Carolin, Fründt, Odette, Garcia-Delgar, Blanca, Gilbert, Donald L, Grice, Dorothy E, Hedderly, Tammy, Heyman, Isobel, Hong, Hyun Ju, Huyser, Chaim, Ibanez-Gomez, Laura, Jakubovski, Ewgeni, Kim, Young Key, Kim, Young Shin, Koh, Yun-Joo, Kook, Sodahm, Kuperman, Samuel, Leventhal, Bennett, Ludolph, Andrea G, Madruga-Garrido, Marcos, Maras, Athanasios, Mir, Pablo, Morer, Astrid, Müller-Vahl, Kirsten, Münchau, Alexander, Murphy, Tara L, Plessen, Kerstin J, Roessner, Veit, Shin, Eun-Young, Song, Dong-Ho, Song, Jungeun, Tübing, Jennifer, van den Ban, Els, Visscher, Frank, Wanderer, Sina, Woods, Martin, Zinner, Samuel H, King, Robert A, Tischfield, Jay A, Heiman, Gary A, Hoekstra, Pieter J, and Dietrich, Andrea

Subjects
Biomedical and Clinical Sciences, Biological Psychology, Clinical Sciences, Neurosciences, Psychology, Brain Disorders, Autism, Genetics, Pediatric, Mental Health, Intellectual and Developmental Disabilities (IDD), Tourette Syndrome, Neurodegenerative, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Mental health, Adolescent, Adult, Child, Child, Preschool, Family Health, Female, Genome-Wide Association Study, Genotype, Humans, Linkage Disequilibrium, Male, Microtubule-Associated Proteins, Middle Aged, Polymorphism, Single Nucleotide, Severity of Illness Index, Tic Disorders, Tryptophan Hydroxylase, Young Adult, Attention-deficit/hyperactivity disorder, Candidate gene study, Obsessive-compulsive disorder, Tourette syndrome, Transmission Disequilibrium Test, Obsessive–compulsive disorder, Cognitive Sciences, Psychiatry, Clinical sciences, Biological psychology
Abstract

Genetic studies in Tourette syndrome (TS) are characterized by scattered and poorly replicated findings. We aimed to replicate findings from candidate gene and genome-wide association studies (GWAS). Our cohort included 465 probands with chronic tic disorder (93% TS) and both parents from 412 families (some probands were siblings). We assessed 75 single nucleotide polymorphisms (SNPs) in 465 parent-child trios; 117 additional SNPs in 211 trios; and 4 additional SNPs in 254 trios. We performed SNP and gene-based transmission disequilibrium tests and compared nominally significant SNP results with those from a large independent case-control cohort. After quality control 71 SNPs were available in 371 trios; 112 SNPs in 179 trios; and 3 SNPs in 192 trios. 17 were candidate SNPs implicated in TS and 2 were implicated in obsessive-compulsive disorder (OCD) or autism spectrum disorder (ASD); 142 were tagging SNPs from eight monoamine neurotransmitter-related genes (including dopamine and serotonin); 10 were top SNPs from TS GWAS; and 13 top SNPs from attention-deficit/hyperactivity disorder, OCD, or ASD GWAS. None of the SNPs or genes reached significance after adjustment for multiple testing. We observed nominal significance for the candidate SNPs rs3744161 (TBCD) and rs4565946 (TPH2) and for five tagging SNPs; none of these showed significance in the independent cohort. Also, SLC1A1 in our gene-based analysis and two TS GWAS SNPs showed nominal significance, rs11603305 (intergenic) and rs621942 (PICALM). We found no convincing support for previously implicated genetic polymorphisms. Targeted re-sequencing should fully appreciate the relevance of candidate genes.

Published
2018

83. Phenomenology of Tics and Sensory Urges

Author

Leckman, James F., additional, Bloch, Michael H., additional, Sukhodolsky, Denis G., additional, Artukoğlu, Bekir B., additional, Scahill, Lawrence, additional, and King, Robert A., additional

Published
2022
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89. Rapid Circumstellar Disk Evolution and an Accelerating Star Formation Rate in the Infrared Dark Cloud M17 SWex

Author

Povich, Matthew S., Townsley, Leisa K., Robitaille, Thomas P., Broos, Patrick S., Orbin, Wesley T., King, Robert R., Naylor, Tim, and Whitney, Barbara A.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Solar and Stellar Astrophysics
Abstract

We present a catalog of 840 X-ray sources and first results from a 100 ks Chandra X-ray Observatory imaging study of the filamentary infrared dark cloud G014.225$-$00.506, which forms the central regions of a larger cloud complex known as the M17 southwest extension (M17 SWex). In addition to the rich population of protostars and young stellar objects with dusty circumstellar disks revealed by Spitzer Space Telescope archival data, we discover a population of X-ray-emitting, intermediate-mass pre--main-sequence stars (IMPS) that lack infrared excess emission from circumstellar disks. We model the infrared spectral energy distributions of this source population to measure its mass function and place new constraints on the inner dust disk destruction timescales for 2-8 $M_{\odot}$ stars. We also place a lower limit on the star formation rate (SFR) and find that it is quite high ($\dot{M}\ge 0.007~M_{\odot}$ yr$^{-1}$), equivalent to several Orion Nebula Clusters in G14.225$-$0.506 alone, and likely accelerating. The cloud complex has not produced a population of massive, O-type stars commensurate with its SFR. This absence of very massive (${\ge}20~M_{\odot}$) stars suggests that either (1) M17 SWex is an example of a distributed mode of star formation that will produce a large OB association dominated by intermediate-mass stars but relatively few massive clusters, or (2) the massive cores are still in the process of accreting sufficient mass to form massive clusters hosting O stars., Comment: 29 pages, 9 figures, accepted to ApJ

Published
2016
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91. Altimetry for the future: Building on 25 years of progress

Author

Abdalla, Saleh, Abdeh Kolahchi, Abdolnabi, Ablain, Michaël, Adusumilli, Susheel, Aich Bhowmick, Suchandra, Alou-Font, Eva, Amarouche, Laiba, Andersen, Ole Baltazar, Antich, Helena, Aouf, Lotfi, Arbic, Brian, Armitage, Thomas, Arnault, Sabine, Artana, Camila, Aulicino, Giuseppe, Ayoub, Nadia, Badulin, Sergei, Baker, Steven, Banks, Chris, Bao, Lifeng, Barbetta, Silvia, Barceló-Llull, Bàrbara, Barlier, François, Basu, Sujit, Bauer-Gottwein, Peter, Becker, Matthias, Beckley, Brian, Bellefond, Nicole, Belonenko, Tatyana, Benkiran, Mounir, Benkouider, Touati, Bennartz, Ralf, Benveniste, Jérôme, Bercher, Nicolas, Berge-Nguyen, Muriel, Bettencourt, Joao, Blarel, Fabien, Blazquez, Alejandro, Blumstein, Denis, Bonnefond, Pascal, Borde, Franck, Bouffard, Jérôme, Boy, François, Boy, Jean-Paul, Brachet, Cédric, Brasseur, Pierre, Braun, Alexander, Brocca, Luca, Brockley, David, Brodeau, Laurent, Brown, Shannon, Bruinsma, Sean, Bulczak, Anna, Buzzard, Sammie, Cahill, Madeleine, Calmant, Stéphane, Calzas, Michel, Camici, Stefania, Cancet, Mathilde, Capdeville, Hugues, Carabajal, Claudia Cristina, Carrere, Loren, Cazenave, Anny, Chassignet, Eric P., Chauhan, Prakash, Cherchali, Selma, Chereskin, Teresa, Cheymol, Cecile, Ciani, Daniele, Cipollini, Paolo, Cirillo, Francesca, Cosme, Emmanuel, Coss, Steve, Cotroneo, Yuri, Cotton, David, Couhert, Alexandre, Coutin-Faye, Sophie, Crétaux, Jean-François, Cyr, Frederic, d’Ovidio, Francesco, Darrozes, José, David, Cedric, Dayoub, Nadim, De Staerke, Danielle, Deng, Xiaoli, Desai, Shailen, Desjonqueres, Jean-Damien, Dettmering, Denise, Di Bella, Alessandro, Díaz-Barroso, Lara, Dibarboure, Gerald, Dieng, Habib Boubacar, Dinardo, Salvatore, Dobslaw, Henryk, Dodet, Guillaume, Doglioli, Andrea, Domeneghetti, Alessio, Donahue, David, Dong, Shenfu, Donlon, Craig, Dorandeu, Joël, Drezen, Christine, Drinkwater, Mark, Du Penhoat, Yves, Dushaw, Brian, Egido, Alejandro, Erofeeva, Svetlana, Escudier, Philippe, Esselborn, Saskia, Exertier, Pierre, Fablet, Ronan, Falco, Cédric, Farrell, Sinead Louise, Faugere, Yannice, Femenias, Pierre, Fenoglio, Luciana, Fernandes, Joana, Fernández, Juan Gabriel, Ferrage, Pascale, Ferrari, Ramiro, Fichen, Lionel, Filippucci, Paolo, Flampouris, Stylianos, Fleury, Sara, Fornari, Marco, Forsberg, Rene, Frappart, Frédéric, Frery, Marie-laure, Garcia, Pablo, Garcia-Mondejar, Albert, Gaudelli, Julia, Gaultier, Lucile, Getirana, Augusto, Gibert, Ferran, Gil, Artur, Gilbert, Lin, Gille, Sarah, Giulicchi, Luisella, Gómez-Enri, Jesús, Gómez-Navarro, Laura, Gommenginger, Christine, Gourdeau, Lionel, Griffin, David, Groh, Andreas, Guerin, Alexandre, Guerrero, Raul, Guinle, Thierry, Gupta, Praveen, Gutknecht, Benjamin D., Hamon, Mathieu, Han, Guoqi, Hauser, Danièle, Helm, Veit, Hendricks, Stefan, Hernandez, Fabrice, Hogg, Anna, Horwath, Martin, Idžanović, Martina, Janssen, Peter, Jeansou, Eric, Jia, Yongjun, Jia, Yuanyuan, Jiang, Liguang, Johannessen, Johnny A., Kamachi, Masafumi, Karimova, Svetlana, Kelly, Kathryn, Kim, Sung Yong, King, Robert, Kittel, Cecile M.M., Klein, Patrice, Klos, Anna, Knudsen, Per, Koenig, Rolf, Kostianoy, Andrey, Kouraev, Alexei, Kumar, Raj, Labroue, Sylvie, Lago, Loreley Selene, Lambin, Juliette, Lasson, Léa, Laurain, Olivier, Laxenaire, Rémi, Lázaro, Clara, Le Gac, Sophie, Le Sommer, Julien, Le Traon, Pierre-Yves, Lebedev, Sergey, Léger, Fabien, Legresy, Benoı̂t, Lemoine, Frank, Lenain, Luc, Leuliette, Eric, Levy, Marina, Lillibridge, John, Liu, Jianqiang, Llovel, William, Lyard, Florent, Macintosh, Claire, Makhoul Varona, Eduard, Manfredi, Cécile, Marin, Frédéric, Mason, Evan, Massari, Christian, Mavrocordatos, Constantin, Maximenko, Nikolai, McMillan, Malcolm, Medina, Thierry, Melet, Angelique, Meloni, Marco, Mertikas, Stelios, Metref, Sammy, Meyssignac, Benoit, Minster, Jean-François, Moreau, Thomas, Moreira, Daniel, Morel, Yves, Morrow, Rosemary, Moyard, John, Mulet, Sandrine, Naeije, Marc, Nerem, Robert Steven, Ngodock, Hans, Nielsen, Karina, Nilsen, Jan Even Øie, Niño, Fernando, Nogueira Loddo, Carolina, Noûs, Camille, Obligis, Estelle, Otosaka, Inès, Otten, Michiel, Oztunali Ozbahceci, Berguzar, P. Raj, Roshin, Paiva, Rodrigo, Paniagua, Guillermina, Paolo, Fernando, Paris, Adrien, Pascual, Ananda, Passaro, Marcello, Paul, Stephan, Pavelsky, Tamlin, Pearson, Christopher, Penduff, Thierry, Peng, Fukai, Perosanz, Felix, Picot, Nicolas, Piras, Fanny, Poggiali, Valerio, Poirier, Étienne, Ponce de León, Sonia, Prants, Sergey, Prigent, Catherine, Provost, Christine, Pujol, M-Isabelle, Qiu, Bo, Quilfen, Yves, Rami, Ali, Raney, R. Keith, Raynal, Matthias, Remy, Elisabeth, Rémy, Frédérique, Restano, Marco, Richardson, Annie, Richardson, Donald, Ricker, Robert, Ricko, Martina, Rinne, Eero, Rose, Stine Kildegaard, Rosmorduc, Vinca, Rudenko, Sergei, Ruiz, Simón, Ryan, Barbara J., Salaün, Corinne, Sanchez-Roman, Antonio, Sandberg Sørensen, Louise, Sandwell, David, Saraceno, Martin, Scagliola, Michele, Schaeffer, Philippe, Scharffenberg, Martin G., Scharroo, Remko, Schiller, Andreas, Schneider, Raphael, Schwatke, Christian, Scozzari, Andrea, Ser-giacomi, Enrico, Seyler, Frederique, Shah, Rashmi, Sharma, Rashmi, Shaw, Andrew, Shepherd, Andrew, Shriver, Jay, Shum, C.K., Simons, Wim, Simonsen, Sebatian B., Slater, Thomas, Smith, Walter, Soares, Saulo, Sokolovskiy, Mikhail, Soudarin, Laurent, Spatar, Ciprian, Speich, Sabrina, Srinivasan, Margaret, Srokosz, Meric, Stanev, Emil, Staneva, Joanna, Steunou, Nathalie, Stroeve, Julienne, Su, Bob, Sulistioadi, Yohanes Budi, Swain, Debadatta, Sylvestre-baron, Annick, Taburet, Nicolas, Tailleux, Rémi, Takayama, Katsumi, Tapley, Byron, Tarpanelli, Angelica, Tavernier, Gilles, Testut, Laurent, Thakur, Praveen K., Thibaut, Pierre, Thompson, LuAnne, Tintoré, Joaquín, Tison, Céline, Tourain, Cédric, Tournadre, Jean, Townsend, Bill, Tran, Ngan, Trilles, Sébastien, Tsamados, Michel, Tseng, Kuo-Hsin, Ubelmann, Clément, Uebbing, Bernd, Vergara, Oscar, Verron, Jacques, Vieira, Telmo, Vignudelli, Stefano, Vinogradova Shiffer, Nadya, Visser, Pieter, Vivier, Frederic, Volkov, Denis, von Schuckmann, Karina, Vuglinskii, Valerii, Vuilleumier, Pierrik, Walter, Blake, Wang, Jida, Wang, Chao, Watson, Christopher, Wilkin, John, Willis, Josh, Wilson, Hilary, Woodworth, Philip, Yang, Kehan, Yao, Fangfang, Zaharia, Raymond, Zakharova, Elena, Zaron, Edward D., Zhang, Yongsheng, Zhao, Zhongxiang, Zinchenko, Vadim, and Zlotnicki, Victor

Published
2021
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96. 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

97. 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

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

Author

Willsey, A Jeremy, Fernandez, Thomas V, Yu, Dongmei, King, Robert A, Dietrich, Andrea, Xing, Jinchuan, Sanders, Stephan J, Mandell, Jeffrey D, Huang, Alden Y, Richer, Petra, Smith, Louw, Dong, Shan, Samocha, Kaitlin E, Tourette International Collaborative Genetics (TIC Genetics), Tourette Syndrome Association International Consortium for Genetics (TSAICG), Neale, Benjamin M, Coppola, Giovanni, Mathews, Carol A, Tischfield, Jay A, Scharf, Jeremiah M, State, Matthew W, and Heiman, Gary A

Subjects
Tourette International Collaborative Genetics, Tourette Syndrome Association International Consortium for Genetics, Humans, Tourette Syndrome, Genetic Predisposition to Disease, Intracellular Signaling Peptides and Proteins, Proteins, Cell Cycle Proteins, Fibronectins, Cadherins, Receptors, Cell Surface, Phosphoproteins, Odds Ratio, Cohort Studies, Sequence Analysis, DNA, Parents, Mutation, Adult, Child, Female, Male, Genetic Variation, TIC Genetics, TSAICG, Tourette disorder, Tourette syndrome, de novo variants, gene discovery, whole-exome sequencing, Biotechnology, Brain Disorders, Human Genome, Neurosciences, Clinical Research, Genetics, 2.1 Biological and endogenous factors, Aetiology, Psychology, Cognitive Sciences, Neurology & Neurosurgery
Abstract

Whole-exome sequencing (WES) and de novo variant detection have proven a powerful approach to gene discovery in complex neurodevelopmental disorders. We have completed WES of 325 Tourette disorder trios from the Tourette International Collaborative Genetics cohort and a replication sample of 186 trios from the Tourette Syndrome Association International Consortium on Genetics (511 total). We observe strong and consistent evidence for the contribution of de novo likely gene-disrupting (LGD) variants (rate ratio [RR] 2.32, p = 0.002). Additionally, de novo damaging variants (LGD and probably damaging missense) are overrepresented in probands (RR 1.37, p = 0.003). We identify four likely risk genes with multiple de novo damaging variants in unrelated probands: WWC1 (WW and C2 domain containing 1), CELSR3 (Cadherin EGF LAG seven-pass G-type receptor 3), NIPBL (Nipped-B-like), and FN1 (fibronectin 1). Overall, we estimate that de novo damaging variants in approximately 400 genes contribute risk in 12% of clinical cases. VIDEO ABSTRACT.

Published
2017

99. 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

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