A5103111402- Amyotrophic Lateral Sclerosis Research
- Neurogenetic and Muscular Disorders Research
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Pulmonary Hypertension Research and Treatments
- RNA regulation and disease
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- Parkinson's Disease Mechanisms and Treatments
- Diabetes and associated disorders
- RNA Research and Splicing
University Medical Center Utrecht
2021-2025
Utrecht University
2025
University of Massachusetts Chan Medical School
2017
Abstract Despite substantial progress, causal variants are identified only for a minority of familial Parkinson’s disease (PD) cases, leaving high-risk pathogenic unidentified 1,2 . To identify such variants, we uniformly processed exome sequencing data 2,184 index PD cases and 69,775 controls. Exome-wide analyses converged on RAB32 as novel gene identifying c.213C > G/p.S71R variant presenting in ~0.7% while observed 0.004% controls (odds ratio 65.5). This was confirmed all via Sanger...
The determinants of severe COVID-19 in healthy adults are poorly understood, which limits the opportunity for early intervention. We present a multiomic analysis using machine learning to characterize genomic basis severity. use single-cell multiome profiling human lungs link genetic signals cell-type-specific functions. discover >1,000 risk genes across 19 cell types, account 77% SNP-based heritability disease. Genetic is particularly focused within natural killer (NK) cells and T cells,...
The genetic basis combined with the sporadic occurrence of amyotrophic lateral sclerosis (ALS) suggests a role de novo mutations in disease pathogenesis. Previous studies provided some evidence for this hypothesis; however, results were conflicting: no genes recurrent occurring identified and different pathways postulated. In study, we analyzed whole-exome data from 82 new patient-parents trios it datasets all previously published ALS (173 total). per patient rate was not higher than...
Sex is an important covariate in all genetic and epigenetic research due to its role the incidence, progression outcome of many phenotypic characteristics human diseases. Amyotrophic lateral sclerosis (ALS) a motor neuron disease with sex bias towards higher incidence males. Here, we report for first time blood-based epigenome-wide association study meta-analysis 9274 individuals after stringent quality control (5529 males 3975 females). We identified total 226 ALS saDMPs (sex-associated...
ABSTRACT The determinants of severe COVID-19 in non-elderly adults are poorly understood, which limits opportunities for early intervention and treatment. Here we present novel machine learning frameworks identifying common rare disease-associated genetic variation, outperform conventional approaches. By integrating single-cell multiomics profiling human lungs to link signals cell-type-specific functions, have discovered validated over 1,000 risk genes underlying across 19 cell types....
Abstract Explaining missing heritability in rare disorders requires effective methods to interpret genetic variants. Sequence-to-function models such as SpliceAI support discovery of splice altering variants but filtering their output identify pathogenic mutations remains challenging. We developed SpliPath address 2 unmet needs this process. First, links the with reference transcriptomics data. This allows users that induce unannotated isoforms selectively expressed disease or patient...