scholarly journals Genome-Wide TDT Analysis in French-Canadian Families with Tourette Syndrome

2010 ◽  
Vol 37 (1) ◽  
pp. 110-112 ◽  
Author(s):  
Jean-Baptiste Rivière ◽  
Judith St-Onge ◽  
Claudia Gaspar ◽  
Sabrina Diab ◽  
Yves Dion ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
French Canadian ◽  
Genome Wide

scholarly journals Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population

2004 ◽  
Vol 9 (3) ◽  
pp. 272-277 ◽  
Author(s):  
A Díaz-Anzaldúa ◽  
◽  
R Joober ◽  
J-B Rivière ◽  
Y Dion ◽  
...  
Keyword(s):  
Association Study ◽  
Tourette Syndrome ◽  
Founder Population ◽  
French Canadian ◽  
Family Based ◽  
Dopaminergic Genes

scholarly journals Validation of genome-wide polygenic risk scores for coronary artery disease in French Canadians

2019 ◽  
Author(s):  
Florian Wünnemann ◽  
Ken Sin Lo ◽  
Alexandra Langford-Avelar ◽  
David Busseuil ◽  
Marie-Pierre Dubé ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Scores ◽  
French Canadian ◽  
French Canadians ◽  
Polygenic Risk ◽  
Genome Wide ◽  
Artery Disease ◽  
The Impact ◽  
Cad Risk

AbstractCoronary artery disease (CAD) represents one of the leading causes of morbidity and mortality worldwide. Given the healthcare risks and societal impacts associated with CAD, their clinical management would benefit from improved prevention and prediction tools. Polygenic risk scores (PRS) based on an individual’s genome sequence are emerging as potentially powerful biomarkers to predict the risk to develop CAD. Two recently derived genome-wide PRS have shown high specificity and sensitivity to identify CAD cases in European-ancestry participants from the UK Biobank. However, validation of the PRS predictive power and transferability in other populations is now required to support their clinical utility. We calculated both PRS (GPSCAD and metaGRSCAD) in French-Canadian individuals from three cohorts totaling 3639 prevalent CAD cases and 7382 controls, and tested their power to predict prevalent, incident and recurrent CAD. We also estimated the impact of the founder French-Canadian familial hypercholesterolemia deletion (LDLR delta > 15kb deletion) on CAD risk in one of these cohorts and used this estimate to calibrate the impact of the PRS. Our results confirm the ability of both PRS to predict prevalent CAD comparable to the original reports (area under the curve (AUC) = 0.72-0.84). Furthermore, the PRS identified about 6-7% of individuals at CAD risk similar to carriers of the LDLR delta > 15kb mutation, consistent with previous estimates. However, the PRS did not perform as well in predicting incident (AUC= 0.56 - 0.60) or recurrent (AUC= 0.56 - 0.60) CAD. This result suggests that additional work is warranted to better understand how ascertainment biases and study design impact PRS for CAD. Collectively, our results confirm that novel, genome-wide PRS are able to predict CAD in French-Canadians; with further improvements, this is likely to pave the way towards more targeted strategies to predict and prevent CAD-related adverse events.

scholarly journals Synaptic processes and immune-related pathways implicated in Tourette Syndrome

2020 ◽  
Author(s):  
Fotis Tsetsos ◽  
Dongmei Yu ◽  
Jae Hoon Sul ◽  
Alden Y. Huang ◽  
Cornelia Illmann ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Ion Channel ◽  
Tourette Syndrome ◽  
Cell Types ◽  
Synaptic Signaling ◽  
Gene Set ◽  
Individual Level ◽  
Genome Wide ◽  
Additional Support

AbstractTourette 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 Tourette Syndrome (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 Trans-synaptic Signaling processes. MAGMA analysis further supported the involvement of the Cell Adhesion and Trans-synaptic Signaling gene set. The Lympho-cytic 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.

Chromosome 11-q24 region in Tourette syndrome: Association and linkage disequilibrium study in the French Canadian population

2005 ◽  
Vol 138A (3) ◽  
pp. 225-228 ◽  
Author(s):  
Adriana Díaz-Anzaldúa ◽  
Jean-Baptiste Rivière ◽  
Marie-Pierre Dubé ◽  
Ridha Joober ◽  
Judith Saint-Onge ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Tourette Syndrome ◽  
French Canadian ◽  
Chromosome 11 ◽  
Canadian Population ◽  
Syndrome Association

scholarly journals Genome-wide Association Study identifies two novel loci for Gilles de la Tourette Syndrome

2021 ◽  
Author(s):  
Fotis Tsetsos ◽  
Apostolia Topaloudi ◽  
Pritesh Jain ◽  
Zhiyu Yang ◽  
Dongmei Yu ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Genome Wide Association Study ◽  
Neurodevelopmental Disorder ◽  
Published Data ◽  
Volume Data ◽  
Polygenic Risk ◽  
Genome Wide ◽  
A Genome ◽  
Risk Scoring ◽  
Significant Locus

Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder of complex genetic architecture, characterized by multiple motor tics and at least one vocal tic persisting for more than one year. We performed a genome-wide meta-analysis integrating a novel TS cohort with previously published data, resulting in a sample size of 6,133 TS individuals and 13,565 ancestry-matched controls. We identified a genome-wide significant locus on chromosome 5q15 and one array-wide significant locus on chromosome 2q24.2. Integration of eQTL, Hi-C and GWAS data implicated the NR2F1 gene and associated lncRNAs within the 5q15 locus, and the RBMS1 gene within the 2q24.2 locus. Polygenic risk scoring using previous GWAS results demonstrated statistically significant ability to predict TS status in the novel cohort. Heritability partitioning identified statistically significant enrichment in brain tissue histone marks, while polygenic risk scoring on brain volume data identified statistically significant associations with right and left putamen volumes. Our work presents novel insights in the neurobiology of TS opening up new directions for future studies.

Collaborative Genome-Wide Association and Copy Number Variation Analysis of Tourette Syndrome

2019 ◽  
Vol 29 ◽  
pp. S736-S737 ◽  
Author(s):  
Jeremiah Scharf ◽  
Dongmei Yu ◽  
Alden Huang ◽  
Fotis Tsetsos ◽  
Peristera Paschou ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Tourette Syndrome ◽  
Copy Number ◽  
Genome Wide Association ◽  
Variation Analysis ◽  
Copy Number Variation Analysis ◽  
Genome Wide ◽  
Number Variation

scholarly journals Rare copy number variants in NRXN1 and CNTN6 increase risk for Tourette syndrome

2016 ◽  
Author(s):  
Alden Y. Huang ◽  
Dongmei Yu ◽  
Lea K. Davis ◽  
Jae-Hoon Sul ◽  
Fotis Tsetsos ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Copy Number ◽  
Genetic Architecture ◽  
Structural Variation ◽  
Copy Number Variants ◽  
European Ancestry ◽  
Genome Wide ◽  
Snp Microarrays ◽  
Increase Risk ◽  
Increase In Risk

Tourette syndrome (TS) is highly heritable, although identification of its underlying genetic cause(s) has remained elusive. We examined a European ancestry sample composed of 2,435 TS cases and 4,100 controls for copy-number variants (CNVs) using SNP microarrays and identified two genome-wide significant loci that confer a substantial increase in risk for TS (NRXN1, OR=20.3, 95%CI [2.6-156.2], p=6.0 × 10−6; CNTN6, OR=10.1, 95% CI [2.3-45.4], p=3.7 × 10−5). Approximately 1% of TS cases carried one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS.

scholarly journals Concordance of Genetic Variation that Increases Risk for Tourette Syndrome and that Influences its Underlying Neurocircuitry

2018 ◽  
Author(s):  
Mary Mufford ◽  
Josh Cheung ◽  
Neda Jahanshad ◽  
Celia van der Merwe ◽  
Linda Ding ◽  
...  
Keyword(s):  
Tourette Syndrome ◽  
Genetic Architecture ◽  
Genome Wide Association Study ◽  
Brain Regions ◽  
Genetic Variations ◽  
Summary Statistics ◽  
Brain Volumes ◽  
Subcortical Brain ◽  
Genome Wide ◽  
A Genome

ABSTRACTBACKGROUNDThere have been considerable recent advances in understanding the genetic architecture of Tourette Syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variations that increase risk for TS - and its main symptom dimensions - influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS.METHODSWe obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4,644 cases and 8,695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP Effect Concordance Analysis (SECA) was used to examine genetic pleiotropy - the same SNP affecting two traits - and concordance - the agreement in SNP effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage Disequilibrium Score Regression (LDSR) was used as validation of SECA.RESULTSSECA revealed significant pleiotropy between TS and putaminal (p=2×10−4) and caudal (p=4×10−4) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume (p=1×10−3). LDSR lent additional support for the association between TS and thalamic volume (p=5.85×10−2). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamic volume (p=1×10−3), as well as concordance between symmetry behaviour and greater putaminal volume (p=7×10−4). Conditional FDR analysis further revealed novel variants significantly associated with TS (p<8×10−7) when conditioning on intracranial (rs2708146, q=0.046; and rs72853320, q=0.035 and hippocampal (rs1922786, q=0.001 volumes respectively.CONCLUSIONThese data indicate concordance for genetic variations involved in disorder risk and subcortical brain volumes in TS. Further work with larger samples is needed to fully delineate the genetic architecture of these disorders and their underlying neurocircuitry.

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