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

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Authors: 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; Scharf, Jeremiah M; 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
Year: 2019
Journal: The American journal of psychiatry
PMID: 30818990
DOI: 10.1176/appi.ajp.2018.18070857
PMCID: PMC6677250

OBJECTIVE: Tourette'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. METHODS: GWAS 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. RESULTS: GWAS 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. CONCLUSIONS: Modulation 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.

#	Section	Preview
20	RESULTS — Genome-wide Association Study	The final GWAS meta-analysis consisted of 8,265,319 SNPs in 4,819 Tourette syndrome cases and 9,488…
21	RESULTS — Genome-wide Association Study	The top SNP in the GWAS meta-analysis, rs2504235, located on chromosome 13q12.2, surpassed the…
22	RESULTS — Targeted Replication	The 39 LD-independent index SNPs with p<1×10−5 were investigated for replication in the deCODE…
23	RESULTS — Targeted Replication	Meta-analysis restricted to these 39 SNPs was conducted using summary statistics from the primary…
24	RESULTS — Heritability and Polygenic Risk Score Analyses	Tourette syndrome SNP-based heritability (h2g) was estimated in the primary GWAS meta-analysis using…
25	RESULTS — Heritability and Polygenic Risk Score Analyses	As the previous estimate of Tourette syndrome h2g from the first Tourette GWAS (h2g LMM=0.58,…
26	RESULTS — Heritability and Polygenic Risk Score Analyses	To explore the hypothesis that the lower heritability of the Tourette GWAS2 sample might have arisen…
27	RESULTS — Tourette syndrome PRS in Multiplex vs. Simplex Families	Since a large proportion of Tourette GWAS1 cases were derived from affected sib-pair families, which…
28	RESULTS — Tourette syndrome PRS in Multiplex vs. Simplex Families	As multiplex Tourette syndrome cases with a Tourette-affected parent or sibling (N=417) demonstrated…
29	RESULTS — Tourette syndrome PRS and Tic Severity	Given the strong enrichment of Tourette aPRS in cases from multiplex families, Tourette/ chronic tic…
30	RESULTS — Tourette syndrome and Tic Spectrum Phenotypes	Given the hypothesis that Tourette and other tic disorders represent a phenotypic spectrum with a…
31	RESULTS — Enrichment of Tourette syndrome heritability by functional annotation and gene expression	Tourette syndrome SNP-based heritability (h2g) from the GWAS meta-analysis was also used as a…
32	RESULTS — Gene-based association and enrichment analyses	Gene-based association and enrichment tests were performed using meta-analysis summary statistics in…
33	DISCUSSION	Tourette syndrome has long been conceptualized as part of a spectrum of developmental tic disorders,…
34	DISCUSSION	within Tourette syndrome cases, the finding that higher Tourette PRS was associated with increased…
35	DISCUSSION	These observations have direct biological and clinical relevance. First, they support previous…
36	DISCUSSION	20-25% of children who present with transient tics (1), and, at the other end of the phenotypic…
37	DISCUSSION	Our genome-wide cell and tissue-based enrichment analyses implicate modulation of gene expression…
38	DISCUSSION — LIMITATIONS	This study has several potential limitations, the most significant of which is the sample size.…

Name	Type
1000 Genomes Project Phase 1 integrated haplotypes local	cohort
39 top LD-independent SNPs local	variant
ADHD	phenotype
affected sib-pair families local	cohort
ancestry-adjusted PRS local	drug
Ancestry-matched controls local	cohort
Ashkenazi Jewish samples local	cohort
attention deficit hyperactivity disorder	phenotype
autism spectrum disorder	phenotype
case-control sample	cohort
cases	cohort
caudate nucleus	anatomy
CELSR3	gene
cerebellum	anatomy
chronic motor or vocal tic disorder local	phenotype
Chronic motor or vocal tic disorder local	phenotype
chronic tic local	phenotype
clinic-based cases local	cohort
CNS cell types local	anatomy
CNTN6 local	gene
complex symmetry local	phenotype
complex symmetry tics local	phenotype
controls	cohort
cortex	anatomy
deCODE controls local	cohort
deCODE sample local	cohort
deCODE samples local	cohort
deCODE tic spectrum cases local	cohort
deCODE Tourette cases local	cohort
dorsolateral pre-frontal cortex local	anatomy
dorsolateral prefrontal cortex	anatomy
EU cases local	cohort
EU controls local	cohort
Evolutionarily-conserved SNPs local	variant
family-based analysis local	cohort
family-based sample	cohort
family history of Tourette local	phenotype
family-history positive Tourette cases local	cohort
first-degree relatives	cohort
FLT3 local	gene
frontal cortex	anatomy
GTEx RNA-seq data local	cohort
GWAS1 local	cohort
GWAS1_AJ local	cohort
GWAS1 cases local	cohort
GWAS1_EU local	cohort
GWAS1_FC local	cohort
GWAS1 sample local	cohort
GWAS1_TIC local	cohort
GWAS2 local	cohort
GWAS2 analyses local	cohort
GWAS2 cases (email recruitment) local	cohort
GWAS2 cases (specialty clinics) local	cohort
GWAS2 FAM local	cohort
GWAS2 FAM sample local	cohort
GWAS2 sample local	cohort
HDC local	gene
Icelandic deCODE sample local	cohort
Icelandic sample local	cohort
Icelandic Tourette syndrome cases local	cohort
index SNP	cohort
MAGMA	drug
Motor tics local	phenotype
multiplex families	cohort
multiplex Tourette syndrome cases local	cohort
non-European ancestry	cohort
NRXN1	gene
nucleus accumbens	anatomy
obsessive-compulsive disorder	phenotype
OCD	phenotype
Other tic disorder cases local	cohort
participants (age >=18) local	cohort
Persistent tic disorders local	phenotype
PGC Tourette Syndrome Workgroup local	cohort
polygenic risk score	cohort
polygenic risk score (aPRS) local	drug
primary meta-analysis local	cohort
probands	cohort
Psychiatric Genomics Consortium	cohort
putamen	anatomy
rs13407215 local	variant
rs1933437 local	variant
rs2504235 local	variant
schizophrenia	phenotype
screened controls	cohort
simplex families	cohort
SLITRK1	gene
SNP	cohort
SNP-based heritability	phenotype
socially inappropriate tics local	phenotype
TIC local	cohort
TIC Genetics sample local	cohort
tic persistence local	phenotype
Tic persistence local	phenotype
tics	phenotype
TIC sample local	cohort
tic severity	phenotype
Tic spectrum disorder local	phenotype
Tic spectrum disorders local	phenotype
top SNPs	cohort
Tourette aPRS local	drug
Tourette Association of America local	cohort
Tourette/chronic tic family-history positive cases local	cohort
Tourette/chronic tic simplex cases local	cohort
Tourette GWAS1 local	cohort
Tourette GWAS cases with chronic tic-affected parent/sibling local	cohort
Tourette PRS local	drug
Tourette syndrome	phenotype
Transient tic disorder local	phenotype
transient tics local	phenotype
Transient tics local	phenotype
UCLA Neuroscience Genomics Core local	cohort
UNGC local	cohort
Unscreened population-matched controls local	cohort
unspecified tic disorder local	phenotype
Vocal tics local	phenotype
web-based cases local	cohort

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Blood metabolites, neurocognition and psychiatric disorders: a Mendelian randomization analysis to investigate causal pathways.	Guo J et al.	—	2024	→
Causal influences of neuropsychiatric disorders on Alzheimer's disease.	Baranova A et al.	—	2024	→
Causal relationships between atopic dermatitis and psychiatric disorders: a bidirectional two-sample Mendelian randomization study.	Cao S et al.	—	2024	→
Circulating retinol and 25(OH)D contents and their association with symptoms in children with chronic tic disorders.	Wang CX et al.	—	2024	→
Cognitive processing speed and accuracy are intrinsically different in genetic architecture and brain phenotypes.	Li M et al.	—	2024	→
Complex interplay of neurodevelopmental disorders (NDDs), fractures, and osteoporosis: a mendelian randomization study.	Li Z et al.	—	2024	→
Cortico-striatal differences in the epigenome in attention-deficit/ hyperactivity disorder.	Shastri GG et al.	—	2024	→
Cytokine expression profiles in children and adolescents with tic disorders.	Kutuk MO et al.	—	2024	→
Deep brain stimulation for Tourette's syndrome.	Aydin S et al.	—	2024	→
Deep brain stimulation for Tourette's syndrome.	Wang S et al.	—	2024	→
Developing a phenotype risk score for tic disorders in a large, clinical biobank.	Miller-Fleming TW et al.	—	2024	→
Diagnostic Criteria for Primary Tic Disorders: Time for Reappraisal.	Sarchioto M et al.	—	2024	→
Discrimination between healthy participants and people with panic disorder based on polygenic scores for psychiatric disorders and for intermediate phenotypes using machine learning.	Ohi K et al.	—	2024	→
Dissecting the genetic and causal relationship between sleep-related traits and common brain disorders.	Xue B et al.	—	2024	→
DNA methylation as a possible mechanism linking childhood adversity and health: results from a 2-sample mendelian randomization study.	Schuurmans IK et al.	—	2024	→
Epilepsy and childhood psychiatric disorders: a two-sample bidirectional Mendelian randomization study.	Wu Y et al.	—	2024	→
Evaluating the distinct effects of body mass index at childhood and adulthood on adult major psychiatric disorders.	Xiao P et al.	—	2024	→
Examination of a novel expression-based gene-SNP annotation strategy to identify tissue-specific contributions to heritability in multiple traits.	Mize TJ et al.	—	2024	→
Gene discovery and biological insights into anxiety disorders from a large-scale multi-ancestry genome-wide association study.	Friligkou E et al.	—	2024	→
Genetic evidence for causal effects of immune dysfunction in psychiatric disorders: where are we?	Iakunchykova O et al.	—	2024	→
Genetic evidence for the causal relations between metabolic syndrome and psychiatric disorders: a Mendelian randomization study.	Gao X et al.	—	2024	→
Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.	Nievergelt CM et al.	—	2024	→
Genome-wide association study identifies DRAM1 associated with Tourette syndrome in Taiwan.	Lin WD et al.	—	2024	→
Genome-Wide Association Study Points to Novel Locus for Gilles de la Tourette Syndrome.	Tsetsos F et al.	—	2024	→
Genomic structural equation modeling reveals latent phenotypes in the human cortex with distinct genetic architecture.	Morey RA et al.	—	2024	→
Identification of immune traits associated with neurodevelopmental disorders by two-sample Mendelian randomization analysis.	Chen J et al.	—	2024	→
Identifying risk loci for obsessive-compulsive disorder and shared genetic component with schizophrenia: A large-scale multi-trait association analysis with summary statistics.	Dai J et al.	—	2024	→
Massively parallel characterization of regulatory elements in the developing human cortex.	Deng C et al.	—	2024	→
Mendelian randomization analyses reveal causal relationships between brain functional networks and risk of psychiatric disorders.	Mu C et al.	—	2024	→
Mendelian randomization analysis of the brain, cerebrospinal fluid, and plasma proteome identifies potential drug targets for attention deficit hyperactivity disorder.	Zhang C et al.	—	2024	→
Mitochondrial related Mendelian randomization identifies causal associations between metabolic disorders and childhood neurodevelopmental disorders.	Hu C et al.	—	2024	→
Neurodevelopmental disorders as a risk factor for temporomandibular disorder: evidence from Mendelian randomization studies.	Wu X et al.	—	2024	→
Neuroticism and posttraumatic stress disorder: A Mendelian randomization analysis.	You Z et al.	—	2024	→
Pharmacological treatment of Tourette's syndrome: from the past to the future.	Gong H et al.	—	2024	→
Psychiatric comorbidities in epilepsy: population co-occurrence, genetic correlations and causal effects.	Ahlqvist VH et al.	—	2024	→
Shared molecular mechanisms and transdiagnostic potential of neurodevelopmental disorders and immune disorders.	Xiu Z et al.	—	2024	→
Structural Variants and Implicated Processes Associated with Familial Tourette Syndrome.	Fichna JP et al.	—	2024	→
The genetic architecture of substance use and its diverse correlations with mental health traits.	Wormington B et al.	—	2024	→
The genetic architecture of the human hypothalamus and its involvement in neuropsychiatric behaviours and disorders.	Chen SD et al.	—	2024	→
The genetics of trichotillomania and excoriation disorder: A systematic review.	Reid M et al.	—	2024	→
The impact of assortative mating, participation bias and socioeconomic status on the polygenic risk of behavioural and psychiatric traits.	Cabrera-Mendoza B et al.	—	2024	→
The interaction effects of age, APOE and common environmental risk factors on human brain structure.	Chen J et al.	—	2024	→
The risk of Alzheimer's disease and cognitive impairment characteristics in eight mental disorders: A UK Biobank observational study and Mendelian randomization analysis.	Liu Y et al.	—	2024	→
The role of neuroactive steroids in tic disorders.	Branca C et al.	—	2024	→
Topologically associating domains define the impact of de novo promoter variants on autism spectrum disorder risk.	Nakamura T et al.	—	2024	→
Tourette Syndrome and Tic Disorders.	Trau SP et al.	—	2024	→
Tourette syndrome research highlights from 2023.	Hartmann A et al.	—	2024	→
Transcriptomic Evaluation of a Stress Vulnerability Network Using Single-Cell RNA Sequencing in Mouse Prefrontal Cortex.	Hing B et al.	—	2024	→
Whole-exome sequencing identifies high-confidence genes for tic disorders in a Chinese Han population.	Lu Q et al.	—	2024	→
Adult-Onset Tourettism in <i>SLC20A2</i>-Associated Primary Familial Brain Calcification.	Reyes NGD et al.	—	2023	→
Associations between brain gene expression perturbations implicated by COVID-19 and psychiatric disorders.	Gao Y et al.	—	2023	→
Behavioral Interventions for Children and Adults with Tic Disorder.	Woods DW et al.	—	2023	→
Calcium Homeostasis and Psychiatric Disorders: A Mendelian Randomization Study.	Jiang M et al.	—	2023	→
Candidate diagnostic biomarkers for neurodevelopmental disorders in children and adolescents: a systematic review.	Cortese S et al.	—	2023	→
Causal associations between COVID-19 and childhood mental disorders.	Chen F et al.	—	2023	→
Causal associations between female reproductive behaviors and psychiatric disorders: a lifecourse Mendelian randomization study.	Yu Y et al.	—	2023	→
Circulating Proteins Influencing Psychiatric Disease: A Mendelian Randomization Study.	Lu T et al.	—	2023	→
Convergent imaging-transcriptomic evidence for disturbed iron homeostasis in Gilles de la Tourette syndrome.	Kanaan AS et al.	—	2023	→
Emerging therapies and recent advances for Tourette syndrome.	Chou CY et al.	—	2023	→
Enrichment of self-domestication and neural crest function loci in the heritability of neurodevelopmental disorders.	Koller D et al.	—	2023	→
Examining the shared etiology of psychopathology with genome-wide association studies.	Mallard TT et al.	—	2023	→
Fine Motor Skills in Children with Tourette Syndrome and their Unaffected First-degree Siblings.	Tygesen MLB et al.	—	2023	→
Functional and molecular characterization of suicidality factors using phenotypic and genome-wide data.	Quintero Reis A et al.	—	2023	→
Genetic patterning for child psychopathology is distinct from that for adults and implicates fetal cerebellar development.	Hughes DE et al.	—	2023	→
Genome-wide association study in 404,302 individuals identifies 7 significant loci for reaction time variability.	Wootton O et al.	—	2023	→
Genomic variants and inferred biological processes in multiplex families with Tourette syndrome.	Fichna JP et al.	—	2023	→
Impact of Tourette Syndrome on Education.	Lund J et al.	—	2023	→
Investigating Direct and Indirect Genetic Effects in Attention-Deficit/Hyperactivity Disorder Using Parent-Offspring Trios.	Martin J et al.	—	2023	→
Is adjustment disorder genetically correlated with depression, anxiety, or risk-tolerant personality trait?	Ohi K et al.	—	2023	→
Machine learning dissection of human accelerated regions in primate neurodevelopment.	Whalen S et al.	—	2023	→
Mapping microRNA expression quantitative trait loci in the prenatal human brain implicates miR-1908-5p expression in bipolar disorder and other brain-related traits.	Toste CC et al.	—	2023	→
Mapping the cortico-striatal transcriptome in attention deficit hyperactivity disorder.	Sudre G et al.	—	2023	→
Molecular Landscape of Tourette's Disorder.	Widomska J et al.	—	2023	→
Molecular programs of regional specification and neural stem cell fate progression in macaque telencephalon.	Micali N et al.	—	2023	→
Multivariate genomic architecture of cortical thickness and surface area at multiple levels of analysis.	Grotzinger AD et al.	—	2023	→
Neuroprotection of Low-Frequency Repetitive Transcranial Magnetic Stimulation after Ischemic Stroke in Rats.	Buetefisch CM et al.	—	2023	→
New insights from the last decade of research in psychiatric genetics: discoveries, challenges and clinical implications.	Andreassen OA et al.	—	2023	→
Novel Functional Genomics Approaches Bridging Neuroscience and Psychiatry.	Restrepo-Lozano JM et al.	—	2023	→
Pervasive Downward Bias in Estimates of Liability-Scale Heritability in Genome-wide Association Study Meta-analysis: A Simple Solution.	Grotzinger AD et al.	—	2023	→
Phosphodiesterase and psychiatric disorders: a two-sample Mendelian randomization study.	Jiang M et al.	—	2023	→
Polygenic and environmental determinants of tics in the Avon Longitudinal Study of Parents and Children.	Abdulkadir M et al.	—	2023	→
Polygenic risk score-based phenome-wide association study identifies novel associations for Tourette syndrome.	Jain P et al.	—	2023	→
Prioritizing genes associated with brain disorders by leveraging enhancer-promoter interactions in diverse neural cells and tissues.	Zhao X et al.	—	2023	→
Shared genetics of psychiatric disorders and type 2 diabetes:a large-scale genome-wide cross-trait analysis.	Ding H et al.	—	2023	→
The interactions between host genome and gut microbiome increase the risk of psychiatric disorders: Mendelian randomization and biological annotation.	Xiao L et al.	—	2023	→
The shared genetic risk factors between Tourette syndrome and obsessive-compulsive disorder.	Khoodoruth MAS et al.	—	2023	→
Tourette syndrome and other tic disorders of childhood.	Nilles C et al.	—	2023	→
Tourette syndrome: clinical features, pathophysiology, and treatment.	Johnson KA et al.	—	2023	→
Tourette syndrome research highlights from 2022.	Hartmann A et al.	—	2023	→
Transcriptome-Wide Structural Equation Modeling of 13 Major Psychiatric Disorders for Cross-Disorder Risk and Drug Repurposing.	Grotzinger AD et al.	—	2023	→
Treatment of Tourette syndrome by acupuncture combined with Chinese medicine based on syndrome differentiation: A review.	Lin K et al.	—	2023	→
Unraveling shared susceptibility loci and Mendelian genetic associations linking educational attainment with multiple neuropsychiatric disorders.	Chen D et al.	—	2023	→
Youth Team Sports Participation Associates With Reduced Dimensional Psychopathology Through Interaction With Biological Risk Factors.	Kunitoki K et al.	—	2023	→
Altered Interoceptive Sensibility in Adults With Chronic Tic Disorder.	Narapareddy A et al.	—	2022	→
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability.	Bae T et al.	—	2022	→
Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.	Yang J et al.	—	2022	→
Associations Between Pregnancy-Related Predisposing Factors for Offspring Neurodevelopmental Conditions and Parental Genetic Liability to Attention-Deficit/Hyperactivity Disorder, Autism, and Schizophrenia: The Norwegian Mother, Father and Child Cohort Study (MoBa).	Havdahl A et al.	—	2022	→
Classifying major mental disorders genetically.	Cao H et al.	—	2022	→
Collective genomic segments with differential pleiotropic patterns between cognitive dimensions and psychopathology.	Lam M et al.	—	2022	→
Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders.	Cabana-Domínguez J et al.	—	2022	→
Cross-ancestry meta-analysis of opioid use disorder uncovers novel loci with predominant effects in brain regions associated with addiction.	Kember RL et al.	—	2022	→
Current understanding of the genetics of tourette syndrome.	Lin WD et al.	—	2022	→
Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration.	Paschou P et al.	—	2022	→
European clinical guidelines for Tourette syndrome and other tic disorders-version 2.0. Part I: assessment.	Szejko N et al.	—	2022	→
Exploring the genetic overlap between twelve psychiatric disorders.	Romero C et al.	—	2022	→
Genetic architecture of 11 major psychiatric disorders at biobehavioral, functional genomic and molecular genetic levels of analysis.	Grotzinger AD et al.	—	2022	→
Genetic estimates of correlation and causality between blood-based biomarkers and psychiatric disorders.	Reay WR et al.	—	2022	→
How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID).	Kennedy HL et al.	—	2022	→
Identification of genetic variants influencing methylation in brain with pleiotropic effects on psychiatric disorders.	Pineda-Cirera L et al.	—	2022	→
Identifying Factors Associated with the Recurrence of Tic Disorders.	Zhang Y et al.	—	2022	→
Identifying pleiotropic genes for complex phenotypes with summary statistics from a perspective of composite null hypothesis testing.	Wang T et al.	—	2022	→
Identity-by-descent analysis of a large Tourette's syndrome pedigree from Costa Rica implicates genes involved in neuronal development and signal transduction.	Ryan N et al.	—	2022	→
Lack of Association of <i>FLT3</i> rs2504235 and Absence of <i>SLITRK1</i> var321 in Patients with Tic Disorders from Guangdong Province, China.	Gao M et al.	—	2022	→
Mendelian randomization analyses support causal relationships between brain imaging-derived phenotypes and risk of psychiatric disorders.	Guo J et al.	—	2022	→
MicroRNA binding site variation is enriched in psychiatric disorders.	Geaghan MP et al.	—	2022	→
Mitochondrial DNA variant spectrum and the association with chronic tic disorders.	Jiang P et al.	—	2022	→
Motor-like Tics are Mediated by CB<sub>2</sub> Cannabinoid Receptor-dependent and Independent Mechanisms Associated with Age and Sex.	Gorberg V et al.	—	2022	→
Neurosurgical management of Tourette syndrome: A literature review and analysis of a case series treated with deep brain stimulation.	Tomskiy AA et al.	—	2022	→
P3b Amplitude and Latency in Tic Disorders: A Meta-Analysis.	Yang Y et al.	—	2022	→
Population-based genetic effects for developmental stuttering.	Polikowsky HG et al.	—	2022	→
Reconstructing SNP allele and genotype frequencies from GWAS summary statistics.	Yang Z et al.	—	2022	→
Relationship between adverse childhood experiences and symptom severity in adult men with Tourette Syndrome.	Yang K et al.	—	2022	→
Sex-heterogeneous SNPs disproportionately influence gene expression and health.	Traglia M et al.	—	2022	→
Shared genetic links between frontotemporal dementia and psychiatric disorders.	Li C et al.	—	2022	→
Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders.	Akingbuwa WA et al.	—	2022	→
The addiction risk factor: A unitary genetic vulnerability characterizes substance use disorders and their associations with common correlates.	Hatoum AS et al.	—	2022	→
The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness.	Reay WR et al.	—	2022	→
Thirty novel sequence variants impacting human intracranial volume.	Nawaz MS et al.	—	2022	→
Transcriptome-wide association study reveals increased neuronal FLT3 expression is associated with Tourette's syndrome.	Liao C et al.	—	2022	→
Trends of Tourette Syndrome in children from 2011 to 2021: A bibliometric analysis.	Yang C et al.	—	2022	→
What Do We Know About the Genetic Architecture of Psychopathology?	Giangrande EJ et al.	—	2022	→
A Comprehensive Evaluation of Cross-Omics Blood-Based Biomarkers for Neuropsychiatric Disorders.	Song W et al.	—	2021	→
A comprehensive gene-centric pleiotropic association analysis for 14 psychiatric disorders with GWAS summary statistics.	Lu H et al.	—	2021	→
Candidate Genes and Pathways Associated with Gilles de la Tourette Syndrome-Where Are We?	Levy AM et al.	—	2021	→
Causal influences of neuroticism on mental health and cardiovascular disease.	Zhang F et al.	—	2021	→
Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations.	Panyard DJ et al.	—	2021	→
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology.	van Rheenen W et al.	—	2021	→
Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.	Yousefi S et al.	—	2021	→
Contextualizing genetic risk score for disease screening and rare variant discovery.	Zhou D et al.	—	2021	→
Elevated common variant genetic risk for tourette syndrome in a densely-affected pedigree.	Halvorsen M et al.	—	2021	→
Elevated Expression of <i>SLC6A4</i> Encoding the Serotonin Transporter (SERT) in Gilles de la Tourette Syndrome.	Hildonen M et al.	—	2021	→
EWAS of Monozygotic Twins Implicate a Role of mTOR Pathway in Pathogenesis of Tic Spectrum Disorder.	Hildonen M et al.	—	2021	→
Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex.	Mich JK et al.	—	2021	→
Genetic architecture of Tourette syndrome: our current understanding.	Domènech L et al.	—	2021	→
Genetic correlates of socio-economic status influence the pattern of shared heritability across mental health traits.	Marees AT et al.	—	2021	→
Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology.	Mullins N et al.	—	2021	→
Genomic relationships across psychiatric disorders including substance use disorders.	Abdellaoui A et al.	—	2021	→
Genomics of Obsessive-Compulsive Disorder-Toward Personalized Medicine in the Era of Big Data.	Szejko N et al.	—	2021	→
Gut Microbiota and Psychiatric Disorders: A Two-Sample Mendelian Randomization Study.	Ni JJ et al.	—	2021	→
Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS.	Peyrot WJ et al.	—	2021	→
Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum.	Yang Z et al.	—	2021	→
Investigation of gene-environment interactions in relation to tic severity.	Abdulkadir M et al.	—	2021	→
Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa.	Adams DM et al.	—	2021	→
Is Persistent Motor or Vocal Tic Disorder a Milder Form of Tourette Syndrome?	Claudio-Campos K et al.	—	2021	→
Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders.	Song W et al.	—	2021	→
Networks in the Field of Tourette Syndrome.	Kleimaker A et al.	—	2021	→
Polygenic risk score as clinical utility in psychiatry: a clinical viewpoint.	Ikeda M et al.	—	2021	→
Sex differences in the genetic regulation of the blood transcriptome response to glucocorticoid receptor activation.	Moore SR et al.	—	2021	→
Synaptic processes and immune-related pathways implicated in Tourette syndrome.	Tsetsos F et al.	—	2021	→
What Have We Learned About the Genetics of Obsessive-Compulsive and Related Disorders in Recent Years?	Mattheisen M et al.	—	2021	→
Whole-exome sequencing identifies genes associated with Tourette's disorder in multiplex families.	Cao X et al.	—	2021	→
A Review of the Current Treatment of Tourette Syndrome.	Seideman MF et al.	—	2020	→
Case Report: DSM-5 misses an edge case in tic disorders nosology.	Black KJ	—	2020	→
Current Status, Diagnosis, and Treatment Recommendation for Tic Disorders in China.	Liu ZS et al.	—	2020	→
Empiric Recurrence Risk Estimates for Chronic Tic Disorders: Implications for Genetic Counseling.	Heiman GA et al.	—	2020	→
Enrichment and Correlation Analysis of Serum miRNAs in Comorbidity Between Arnold-Chiari and Tourette Syndrome Contribute to Clarify Their Molecular Bases.	Mirabella F et al.	—	2020	→
Gilles de la Tourette Syndrome-A Disorder of Action-Perception Integration.	Kleimaker A et al.	—	2020	→
Heterogeneity and Polygenicity in Psychiatric Disorders: A Genome-Wide Perspective.	Wendt FR et al.	—	2020	→
Massively parallel techniques for cataloguing the regulome of the human brain.	Townsley KG et al.	—	2020	→
Neurobiological functions of transcriptional enhancers.	Nord AS et al.	—	2020	→
Pairwise common variant meta-analyses of schizophrenia with other psychiatric disorders reveals shared and distinct gene and gene-set associations.	Reay WR et al.	—	2020	→
Polygenic risk for autism spectrum disorder associates with anger recognition in a neurodevelopment-focused phenome-wide scan of unaffected youths from a population-based cohort.	Wendt FR et al.	—	2020	→
Refractory Gilles de la Tourette Syndrome-Many Pieces That Define the Puzzle.	Szejko N et al.	—	2020	→
Sex differences in movement disorders.	Meoni S et al.	—	2020	→
Translating insights from neuropsychiatric genetics and genomics for precision psychiatry.	Rees E et al.	—	2020	→
Treatment options for tic disorders.	Rizzo R et al.	—	2020	→
Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders.	Cross-Disorder Group of the Psychiatric Genomics Consortium. Electronic address: plee0@mgh.harvard.edu et al.	—	2019	→
Immunity in Gilles de la Tourette-Syndrome: Results From a Cerebrospinal Fluid Study.	Baumgaertel C et al.	—	2019	→
Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update. II. Hyperkinetic disorders.	Jellinger KA	—	2019	→
Tic disorders revisited: introduction of the term "tic spectrum disorders".	Müller-Vahl KR et al.	—	2019	→
Tourette syndrome research highlights from 2018.	Rose O et al.	—	2019	→