Early preschool wheeze trajectories are predominantly non-allergic with distinct biologic and microbiome traits.

Background: Disentangling preschool wheezing heterogeneity in terms of clinical traits, temporal patterns, and collective healthcare burden is critical for precise and effective interventions.

Objective: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.

Methods: Group-based trajectory analysis was performed in the CHILD Cohort study to identify distinct wheeze and allergic sensitization trajectories.

Novel germline and somatic variants in familial and sporadic meningioma genes.

Meningiomas arise from arachnoid cells in the meninges surrounding the brain and spinal cord and are attributed to NF2 pathogenic variants in, approximately 60% of cases. Using exome sequencing, we found heterozygous germline variants in nine potential novel meningioma genes across four families and four sporadic cases. We then screened for germline and somatic variants in these genes and 11 known meningioma genes in 76 sporadic meningiomas blood/tumor pairs.

Gene-by-environment interactions modulate the infant gut microbiota in asthma and atopy.

Background: Gut microbiota has been associated with health and susceptibility to childhood diseases, including asthma and allergies. However, the genomic factors contributing to interindividual variations in gut microbiota remain poorly understood.

Objective: We sought to integrate host genomics with early-life exposures to investigate main and interaction effects on gut microbiota during the first year of life.

Persistent DNA Methylation Changes across the First Year of Life and Prenatal Exposure in a Canadian Prospective Birth Study.

Background: Evidence suggests that prenatal air pollution exposure alters DNA methylation (DNAm), which could go on to affect long-term health. It remains unclear whether DNAm alterations present at birth persist through early life. Identifying persistent DNAm changes would provide greater insight into the molecular mechanisms contributing to the association of prenatal air pollution exposure with atopic diseases.

Wheeze trajectories: Determinants and outcomes in the CHILD Cohort Study.

Background: Wheezing in early life is associated with asthma in adulthood; however, the determinants of wheezing trajectories and their associations with asthma and lung function in childhood remain poorly understood.

Objective: In the CHILD Cohort Study, we aimed to identify wheezing trajectories and examine the associations between these trajectories, risk factors, and clinical outcomes at age 5 years.

Methods: Wheeze data were collected at 8 time points from 3 months to 5 years of age.

Exome sequencing of sporadic childhood-onset schizophrenia suggests the contribution of X-linked genes in males.

Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia, defined as having an onset before the age of 13. The male COS cases have a slightly younger age of onset than female cases. They also present with a higher rate of comorbid developmental disorders.

Absence of Mutation Enrichment for Genes Phylogenetically Conserved in the Olivocerebellar Motor Circuitry in a Cohort of Canadian Essential Tremor Cases.

Essential Tremor is a prevalent neurological disorder of unknown etiology. Studies suggest that genetic factors contribute to this pathology. To date, no causative mutations in a gene have been reproducibly reported.

Missense variants in ATP1A3 and FXYD gene family are associated with childhood-onset schizophrenia.

Childhood-onset schizophrenia (COS) is a rare and severe form of schizophrenia defined as onset before age of 13. Here we report on two unrelated cases diagnosed with both COS and alternating hemiplegia of childhood (AHC), and for whom two distinct pathogenic de novo variants were identified in the ATP1A3 gene. ATP1A3 encodes the α-subunit of a neuron-specific ATP-dependent transmembrane sodium-potassium pump.

Full sequencing and haplotype analysis of MAPT in Parkinson's disease and rapid eye movement sleep behavior disorder.

Background: MAPT haplotypes are associated with PD, but their association with rapid eye movement sleep behavior disorder is unclear.

Objective: To study the role of MAPT variants in rapid eye movement sleep behavior disorder.

Methods: Two cohorts were included: (A) PD (n = 600), rapid eye movement sleep behavior disorder (n = 613) patients, and controls (n = 981); (B) dementia with Lewy bodies patients with rapid eye movement sleep behavior disorder (n = 271) and controls (n = 950).

A rare variant in MLKL confers susceptibility to ApoE ɛ4-negative Alzheimer's disease in Hong Kong Chinese population.

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. To identify rare genetic factors other than apolipoprotein E ɛ4 allele (ApoE ɛ4) contributing to the pathogenesis of late-onset AD (LOAD), we conducted a whole-exome analysis of 246 ApoE ɛ4-negative LOAD cases and 172 matched controls in Hong Kong Chinese population. LOAD patients showed a significantly higher burden of rare loss-of-function variants in genes related to immune function than healthy controls.

No rare deleterious variants from , , and are associated with essential tremor.

Objective: To assess the contribution of variants in , , and as essential tremor (ET) predisposing factors following their association in a 2-stage genome-wide association study (GWAS).

Methods: The coding regions of these genes was examined for the presence of rare variants using two approaches: (1) Looking at whole-exome and whole-genome sequencing data of 14 autosomal dominant multiplex ET families. (2) Conducting a targeted massive parallel sequencing to examine the three genes in cohorts of 269 ET cases and 287 control individuals.

Teneurin transmembrane protein 4 is not a cause for essential tremor in a Canadian population.

Introduction: Mutations in teneurin transmembrane protein 4 were reported to be a risk factor for essential tremor, but the relevance of this across different population remains to be examined. The aim of this study was to determine the frequency and spectrum of variations in teneurin transmembrane protein 4 in a cohort of Canadian essential tremor cases.

Methods: The coding portion of teneurin transmembrane protein 4 was sequenced in 269 unrelated essential tremor cases and 288 matched control individuals using a targeted and high-throughput sequencing approach.

RNF213 Is Associated with Intracranial Aneurysms in the French-Canadian Population.

Intracranial aneurysms (IAs) are the result of focal weakness in the artery wall and have a complex genetic makeup. To date, genome-wide association and sequencing studies have had limited success in identifying IA risk factors. Distinct populations, such as the French-Canadian (FC) population, have increased IA prevalence.

Paternal Age Explains a Major Portion of De Novo Germline Mutation Rate Variability in Healthy Individuals.

De novo mutations (DNM) are an important source of rare variants and are increasingly being linked to the development of many diseases. Recently, the paternal age effect has been the focus of a number of studies that attempt to explain the observation that increasing paternal age increases the risk for a number of diseases. Using disease-free familial quartets we show that there is a strong positive correlation between paternal age and germline DNM in healthy subjects.

GBA p.T369M substitution in Parkinson disease: Polymorphism or association? A meta-analysis.

The lysosomal enzyme glucocerebrosidase (GCase), encoded by GBA, has an important role in Parkinson disease (PD). GBA mutation carriers have an increased risk for PD, earlier age at onset, faster progression, and various nonmotor symptoms including cognitive decline, REM sleep behavior disorder, hyposmia, and autonomic dysfunction.(1) Furthermore, GCase enzymatic activity is reduced in the peripheral blood(2) and brain(3) of noncarrier, sporadic PD patients.

Identification of genetic variants of LGI1 and RTN4R (NgR1) linked to schizophrenia that are defective in NgR1-LGI1 signaling.

Background: The protein NgR1 is encoded by RTN4R, a gene linked to schizophrenia. We previously reported NgR1 as receptor for the epilepsy-linked protein LGI1. NgR1 regulates synapse number and synaptic plasticity, whereas LGI1 antagonizes NgR1 signaling and promotes synapse formation.

Analysis of DNAJC13 mutations in French-Canadian/French cohort of Parkinson's disease.

DNAJC13 mutations have been suggested to cause Parkinson's disease (PD), yet subsequent studies reported conflicting results on this association. In the present study, we sequenced the coding region of DNAJC13 in a French-Canadian/French cohort of 528 PD patients and 692 controls. A total of 62 (11.