A5050905725- Congenital heart defects research
- Congenital Heart Disease Studies
- Genomic variations and chromosomal abnormalities
- Coronary Artery Anomalies
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Diet, Metabolism, and Disease
- Autism Spectrum Disorder Research
- RNA Research and Splicing
- Genomics and Phylogenetic Studies
- Genetic Neurodegenerative Diseases
- Infective Endocarditis Diagnosis and Management
- Lipid metabolism and disorders
- Cardiovascular Function and Risk Factors
- Tracheal and airway disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Tissue Engineering and Regenerative Medicine
- Chromosomal and Genetic Variations
- RNA and protein synthesis mechanisms
- Genetic factors in colorectal cancer
- Psychosomatic Disorders and Their Treatments
- Optimism, Hope, and Well-being
- Liver Disease Diagnosis and Treatment
- Dialysis and Renal Disease Management
University Health Network
2017-2025
Centre for Addiction and Mental Health
2016-2025
Toronto General Hospital
2019-2025
Western University
2023
University of Toronto
2017-2023
Hospital for Sick Children
2020-2023
SickKids Foundation
2023
Child and Family Research Institute
2022
Toronto General Hospital Research Institute
2022
Children's Hospital of Eastern Ontario
2021
Abstract Copy number variations (CNVs) are implicated across many neurodevelopmental disorders (NDDs) and contribute to their shared genetic etiology. Multiple studies have attempted identify etiology among NDDs, but this is the first genome-wide CNV analysis autism spectrum disorder (ASD), attention deficit hyperactivity (ADHD), schizophrenia (SCZ), obsessive-compulsive (OCD) at once. Using microarray (Affymetrix CytoScan HD), we genotyped 2,691 subjects diagnosed with an NDD (204 SCZ,...
<h3>Background:</h3> Although pathogenic 22q11.2 deletions are an important cause of developmental delays and lifelong disease burden, their variable complex clinical expression contributes to under-recognition, delayed molecular diagnosis uncertainty about prevalence. We sought estimate the contemporary live-birth prevalence typical using a population-based newborn screening sample examine data available for associated features. <h3>Methods:</h3> Using DNA from unbiased 12% all dried blood...
Chromosome 22q11.2 deletion syndrome (22q11.2DS) is associated with a more than 20-fold increased risk for developing schizophrenia. The aim of this study was to identify additional genetic factors (i.e., "second hits") that may contribute schizophrenia expression.
To determine disease-associated single-gene variants in conotruncal defects, particularly tetralogy of Fallot (TOF).We analyzed for rare loss-of-function and deleterious FLT4 (VEGFR3) other genes the vascular endothelial growth factor (VEGF) pathway, as part a genome sequencing study involving 175 adults with TOF from single site.We identified nine (5.1%) probands novel variants: seven loss-of-function, including an 8-kb deletion, two predicted damaging. In ten we found likely disruptive...
Clinical molecular testing has been available for 22q11.2 deletion syndrome (22q11.2DS) over two decades yet under‐recognition and diagnostic delays are common. To characterize the “diagnostic odyssey” in 22q11.2DS we studied 202 well‐characterized unrelated adults, none ascertained through an affected relative. We used a regression model to identify clinical demographic factors associated with length of time diagnosis. Kaplan–Meier analysis compared diagnosis era (since 1994) earlier birth...
Abstract Tandem repeat expansions (TREs) can cause neurological diseases but their impact in schizophrenia is unclear. Here we analyzed genome sequences of adults with and found that they have a higher burden TREs are near exons rare the general population, compared non-psychiatric controls. These disproportionately at loci known to be associated from genome-wide association studies, individuals clinically-relevant genetic variants other loci, families where multiple schizophrenia. We showed...
Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk adults with this microdeletion syndrome.
Background: Information about the impact on adult healthcare system is limited for complex rare paediatric diseases, despite their increasing collective prevalence that has paralleled advances in clinical care of children.Within a population-based context, we examined costs and multimorbidity adults with an exemplar contemporary genetic diagnostics.Methods: We estimated direct over 18-year period molecularlyconfirmed 22q11.2microdeletion (cases) matched controls (total 60,459 person-years...
Recent genome-wide studies of rare genetic variants have begun to implicate novel mechanisms for tetralogy Fallot (TOF), a severe congenital heart defect (CHD). To provide statistical support case-only data without parental genomes, we re-analyzed genome sequences 231 individuals with TOF (n = 175) or related CHD. We adapted burden test originally developed de novo assess ultra-rare variant in individual genes, and gene-sets corresponding functional pathways mouse phenotypes, accounting...
The rising prevalence of metabolic syndrome among young adults has prompted studies fasting triglyceride-glucose (TyG) index as a marker insulin resistance. We aimed to evaluate in using non-fasting TyG and high-risk genetic model, 22q11.2 microdeletion. assessed its components 350 (50.6% female) aged 18-59 (median 27.7, IQR 22.5-38.1) years with typical microdeletions. used multivariable logistic regression receiver operating characteristic (ROC) curves the association syndrome. Non-fasting...
BackgroundThe 22q11.2 microdeletion is the pathogenic copy number variation (CNV) associated with deletion syndrome (22q11.2DS, formerly known as DiGeorge syndrome). Familiar endocrinological manifestations include hypoparathyroidism and hypothyroidism, recent elucidation of elevated risk for obesity in adults. In this study, we aimed to determine whether adults 22q11.2DS have an increased developing type 2 diabetes (T2D).MethodsWe studied effect on T2D, defined by history glycosylated...
Abstract The range of genetic variation with potential clinical implications in schizophrenia, beyond rare copy number variants (CNVs), remains uncertain. We therefore analyzed genome sequencing data for 259 unrelated adults schizophrenia from a well-characterized community-based cohort previously examined chromosomal microarray CNVs (none 22q11.2 deletions). these genomes high-impact considered causal neurodevelopmental disorders, including single-nucleotide (SNVs) and small...
Mild to moderate hypertriglyceridemia is a condition often associated with obesity and diabetes, as yet incomplete knowledge of underlying genetic architecture. The 22q11.2 microdeletion multimorbidity, including increased risk diabetes. In this study, we sought investigate whether the was mild (1.7-10 mmol/L).This cohort study comparing 6793 population-based adults 267 aged 17-69 years, excluding those diabetes or on statins.We used binomial logistic regression modeling identify predictors...
The 22q11.2 deletion is associated with >20-fold increased risk for schizophrenia. presence of gene DGCR8 in the region has suggested microRNA (miRNA) dysregulation as possibly contributing to this risk. We therefore investigated role miRNA target genes context previously identified genome-wide schizophrenia conveyed by additional copy number variation (CNV) syndrome (22q11.2DS). Using a cohort individuals 22q11.2DS and documented rare CNVs overlapping protein coding genes, we compared those...
Elevated triglyceride (TG) levels are a heritable and modifiable risk factor for cardiovascular disease have well-established associations with common genetic variation captured in polygenic score (PRS). In young adulthood, the 22q11.2 microdeletion conveys 2-fold increased mild-moderate hypertriglyceridemia. This study aimed to assess role of TG-PRS individuals this elevated baseline hypertriglyceridemia.We studied deeply phenotyped cohort adults (n = 157, median age 34 years) available...
Abstract Background Genotype-first and within-family studies can elucidate factors that contribute to psychiatric illness. Combining these approaches, we investigated the patterns of influence parental scores, a high-impact variant, schizophrenia on dimensional neurobehavioral phenotypes implicated in major disorders. Methods We quantitatively assessed cognitive (FSIQ, VIQ, PIQ), social, motor functioning 82 adult individuals with de novo 22q11.2 deletion (22 schizophrenia), 148 their...
The 22q11.2 microdeletion and its associated conditions could affect reproductive outcomes but there is limited information on this important area. We investigated in a sample of 368 adults with typical deletions (median age 32.8, range 17.9–76.3 years; 195 females), without moderate-severe intellectual disability, who were followed prospectively. examined all possible effects diagnosis as transmitting parent these outcomes. used logistic regression to investigate factors relevant fitness...
We aimed to evaluate adult-onset obstructive sleep apnea (OSA) and related risk factors, including history of pediatric palatal/pharyngeal surgery remediate velopharyngeal dysfunction, in 22q11.2 deletion syndrome (22q11.2DS).Using a retrospective cohort design standard study-based criteria, we determined presence OSA (age ≥16 years) relevant variables through comprehensive chart review well-characterized 387 adults with typical microdeletions (51.4% female, median age 32.3, interquartile...
The 22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion disorder. Why incidence of 22q11.2DS much greater than that other genomic disorders remains unknown. Short read sequencing cannot resolve complex segmental duplicon structure to provide direct confirmation hypothesis rearrangements are caused by nonallelic homologous recombination between low copy repeats on Chromosome 22 (LCR22s). To enable haplotype-specific assembly and rearrangement mapping in LCR22 regions, we...