Allison A. Dilliott
A5035345962- Amyotrophic Lateral Sclerosis Research
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- Alzheimer's disease research and treatments
- Dementia and Cognitive Impairment Research
- Neurological diseases and metabolism
- RNA Research and Splicing
- Traumatic Brain Injury and Neurovascular Disturbances
- Cerebral Palsy and Movement Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Cerebrovascular and genetic disorders
- Cerebrospinal fluid and hydrocephalus
- Stroke Rehabilitation and Recovery
- Parkinson's Disease Mechanisms and Treatments
- Acute Ischemic Stroke Management
- Bioinformatics and Genomic Networks
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- BRCA gene mutations in cancer
- Congenital Ear and Nasal Anomalies
- Genetics and Neurodevelopmental Disorders
- Balance, Gait, and Falls Prevention
- Neurological Disease Mechanisms and Treatments
- Lipid metabolism and disorders
- Eicosanoids and Hypertension Pharmacology
Montreal Neurological Institute and Hospital
2022-2025
McGill University
2022-2025
Health Sciences Centre
2024
Sunnybrook Health Science Centre
2024
Western University
2015-2023
Robarts Clinical Trials
2018-2023
Novartis (Canada)
2019
Montreal Heart Institute
2016
Université de Montréal
2016
Objective— Next-generation sequencing technology is transforming our understanding of heterozygous familial hypercholesterolemia, including revision prevalence estimates and attribution polygenic effects. Here, we examined the contributions monogenic factors in patients with severe hypercholesterolemia referred to a specialty clinic. Approach Results— We applied targeted next-generation custom annotation, coupled evaluation large-scale copy number variation scores for raised low-density...
Amyotrophic lateral sclerosis (ALS) is a complex disease that leads to motor neuron death. Despite heritability estimates of 52%, genome-wide association studies (GWASs) have discovered relatively few loci. We developed machine learning approach called RefMap, which integrates functional genomics with GWAS summary statistics for gene discovery. With transcriptomic and epigenetic profiling neurons derived from induced pluripotent stem cells (iPSCs), RefMap identified 690 ALS-associated genes...
Background Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case–control statistical evidence implicating oligogenicity with disease or clinical outcomes is limited. Considering its direct and therapeutic implications, we aim to perform large-scale robust investigation of ALS the course. Methods We leveraged Project MinE genome sequencing datasets (6711 cases 2391 controls) identify associations between known genes risk, as well...
Plasma biomarkers of Alzheimer disease (AD), neuroinflammation, and neurodegeneration are increasingly being used in clinical trials for diagnosis monitoring dementia. However, their association with longitudinal structural brain MRI changes, an important outcome measure across neurodegenerative cerebrovascular diseases, is less known. We investigated how baseline plasma reflect markers progression over time patients diseases. This cohort study included from the Ontario Neurodegenerative...
Abstract Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location severity disease processes via saccade parameters measured from eye movement such as prosaccade antisaccade. Existing studies typically examine few in single diseases, using multiple separate neuropsychological test scores to relate behaviour cognition; however, this approach produces inconsistent,...
Abstract INTRODUCTION We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across within neurodegenerative diseases. METHODS Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p‐tau)181 amyloid beta (Aβ) 42/40 were measured using ultra‐sensitive Simoa immunoassays 44 healthy controls 480 participants diagnosed Alzheimer's disease/mild impairment...
Abstract INTRODUCTION Apolipoprotein E E4 allele ( APOE E4) and slow gait are independently associated with cognitive impairment dementia. However, it is unknown whether their coexistence poorer performance its underlying mechanism in neurodegenerative diseases. METHODS Gait speed, E4, cognition, neuroimaging were assessed 480 older adults neurodegeneration. Participants grouped by presence gait. Mediation analyses conducted to determine if brain structures could explain the link between...
Abstract Introduction/Aims Genetics is an important risk factor for amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting motor neurons. Recent findings demonstrate that in addition to specific genetic mutations, structural variants caused by instability can also play causative role ALS. Genomic lead deletions, duplications, insertions, inversions, and translocations the genome, these changes sometimes fusion of distinct genes into single transcript. Gene events have...
Next-generation sequencing (NGS) is quickly revolutionizing how research into the genetic determinants of constitutional disease performed. The technique highly efficient with millions reads being produced in a short time span and at relatively low cost. Specifically, targeted NGS able to focus investigations genomic regions particular interest based on study. Not only does this further reduce costs increase speed process, but it lessens computational burden that often accompanies NGS....
Abstract Introduction Understanding synergies between neurodegenerative and cerebrovascular pathologies that modify dementia presentation represents an important knowledge gap. Methods This multi‐site, longitudinal, observational cohort study recruited participants across prevalent diseases disease assessed comprehensively modalities. We describe univariate multivariate baseline features of the summarize recruitment, data collection, curation processes. Results enrolled 520 five diseases....
Abstract The Ontario Neurodegenerative Disease Research Initiative (ONDRI) is a multimodal, multi-year, prospective observational cohort study to characterise five diseases: (1) Alzheimer’s disease (AD) or amnestic single multidomain mild cognitive impairment (aMCI) (AD/MCI); (2) amyotrophic lateral sclerosis (ALS); (3) frontotemporal dementia (FTD); (4) Parkinson’s (PD); and (5) vascular (VCI). ONDRI Genomics subgroup investigating the genetic basis of neurodegeneration. We have developed...
Objective: Genetic determinants of severe hypertriglyceridemia include both common variants with small effects (assessed using polygenic risk scores) plus heterozygous and homozygous rare in canonical genes directly affecting triglyceride metabolism. Here, we broadened our scope to detect associations loss-of-function noncanonical pathways, including those known affect metabolism indirectly. Approach Results: From targeted next-generation sequencing 69 metabolism-related 265 patients...
Genetic factors contribute to neurodegenerative diseases, with high heritability estimates across diagnoses; however, a large portion of the genetic influence remains poorly understood. Many previous studies have attempted fill gaps by performing linkage analyses and association in individual disease cohorts, but failed consider clinical pathological overlap observed diseases potential for between phenotypes. Here, we leveraged rare variant (RVAAs) elucidate among multiple diagnoses,...
White matter hyperintensities (WMH) on magnetic resonance imaging may influence clinical presentation in patients with Parkinson's disease (PD), although their significance and pathophysiological origins remain unresolved. Studies examining WMH have identified pathogenic variants NOTCH3 as an underlying cause of inherited forms cerebral small vessel disease.We examined variants, volumes, correlates 139 PD the Ontario Neurodegenerative Disease Research Initiative cohort.We 13 (~9%) rare (<1%...
Abstract Multiplexing samples from distinct individuals prior to sequencing is a promising step toward achieving population-scale single-cell RNA by reducing the restrictive costs of technology. Individual genetic demultiplexing tools resolve donor-of-origin identity pooled cells using natural variation but present diminished accuracy on highly multiplexed experiments, impeding analytic potential dataset. In response, we introduce Ensemblex: an accuracy-weighted, ensemble framework that...
Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic [EpOME] 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods Results Participants mild moderate stroke or large were selected based on clinical imaging criteria. Metabolites quantified by ultra-high-performance liquid...
Acute change in gait speed while performing a mental task [dual-task cost (DTC)], and hyperintensity magnetic resonance imaging signals white matter are both important disability predictors older individuals with history of stroke (poststroke). It is still unclear, however, whether DTC associated overall volume from specific major brain regions poststroke.This cohort study total 123 (69 ± 7 years age) participants were included the Ontario Neurodegenerative Disease Research Initiative....
Choanal atresia is rarely reported in Kabuki syndrome, but a common feature of CHARGE syndrome. Otherwise, the two conditions have number overlapping features, and molecular links between them recently been elucidated. Here, we report case mother her children who presented with congenital choanal atresia. We performed whole exome sequencing on DNA from unaffected parents, identified de novo, novel variant KMT2D. KMT2D p.Gln3575His segregated disease status family, associated unique conserved...