Maria J. Knol
A5052163713- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Dementia and Cognitive Impairment Research
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Alzheimer's disease research and treatments
- Health, Environment, Cognitive Aging
- Congenital heart defects research
- Fetal and Pediatric Neurological Disorders
- Craniofacial Disorders and Treatments
- Genetic Mapping and Diversity in Plants and Animals
- Cerebrospinal fluid and hydrocephalus
- Cancer-related Molecular Pathways
- Functional Brain Connectivity Studies
- Cerebrovascular and genetic disorders
- Ocular Disorders and Treatments
- Nerve injury and regeneration
- Genomics and Rare Diseases
- Bone Metabolism and Diseases
- Neurological Disease Mechanisms and Treatments
- Neurological diseases and metabolism
- Telomeres, Telomerase, and Senescence
- Multiple Sclerosis Research Studies
- Lipoproteins and Cardiovascular Health
Erasmus MC
2017-2025
Erasmus University Rotterdam
2017-2023
Karagandy State University
2023
University of Edinburgh
2022
German Center for Neurodegenerative Diseases
2022
Medical University of Graz
2022
National University of Singapore
2022
Stanford University
2022
The University of Texas Health Science Center at San Antonio
2022
Hudson Institute
2020
Significance The difference between brain age estimated from MRI and chronological is thought to serve as an important biomarker reflecting pathological processes in the brain. Several recent studies showed relation accelerated aging various disorders. However, until now, utility of such for preclinical screening using longitudinal was absent. To fill this gap, we first built a deep learning model population-based study including 5,496 participants. And then, follow-up information, observed...
Abstract Perivascular space (PVS) burden is an emerging, poorly understood, magnetic resonance imaging marker of cerebral small vessel disease, a leading cause stroke and dementia. Genome-wide association studies in up to 40,095 participants (18 population-based cohorts, 66.3 ± 8.6 yr, 96.9% European ancestry) revealed 24 genome-wide significant PVS risk loci, mainly the white matter. These were associated with matter already young adults ( N = 1,748; 22.1 2.3 yr) enriched early-onset...
Importance Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective To investigate causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and while accounting for potential epidemiologic biases. Design, Setting, Participants This study first examined genetically determined WMH BP levels with Alzheimer (AD) in 2-sample mendelian...
To identify common genetic variants associated with the presence of brain microbleeds (BMBs).We performed genome-wide association studies in 11 population-based cohort and 3 case-control or case-only stroke cohorts. Genotypes were imputed to Haplotype Reference Consortium 1000 Genomes reference panel. BMBs rated on susceptibility-weighted T2*-weighted gradient echo MRI sequences, further classified as lobar mixed (including strictly deep infratentorial, possibly BMB). In a subset, we...
Perivascular spaces (PVS) are emerging markers of cerebral small vessel disease (CSVD), but research on their determinants has been hampered by conflicting results from single studies using heterogeneous rating methods. In this study, we therefore aimed to identify PVS burden in a pooled analysis multiple cohort 1 harmonized method.Individuals 10 population-based with adult participants the Uniform Neuro-Imaging Virchow-Robin Spaces Enlargement consortium and UK Biobank were included. On MRI...
The size of the human head is highly heritable, but genetic drivers its variation within general population remain unmapped. We perform a genome-wide association study on (N = 80,890) and identify 67 loci, which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, most have widespread effects. Gene set enrichment observed for various cancers p53, Wnt, ErbB signaling pathways. Genes harboring lead enriched macrocephaly syndrome genes (37-fold) high-fidelity...
Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification multiple genetic variants associated with this highly heritable condition, its architecture remains incompletely understood. More specifically, role DNA methylation has received little attention. We investigated association between hyperintensity burden in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites 9732...
To establish trajectories of cognitive and motor function, to determine the sequence change across individual tests in community-dwelling individuals aged 45-90 years. Between 1997 2016, we repeatedly assessed function with 5 9514 participants years from population-based Rotterdam Study. 1999 measured 3 8297 participants. All were free dementia, stroke, parkinsonism. We overall education-specific using linear mixed models age as time scale. Next, determined tests. The number assessments per...
Abstract Introduction There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants Aβ levels may elucidate important biological processes that determine measures. Methods We included 12,369 non‐demented participants from eight population‐based studies. Imputed data and measured Aβ1‐40, Aβ1‐42 Aβ1‐42/Aβ1‐40 ratio were used to perform genome‐wide association studies, gene‐based pathway analyses. Significant...
<title>Abstract</title> Peak width of skeletonized mean diffusivity (PSMD) is an emerging automated diffusion imaging marker showing clinically relevant changes in cerebral small vessel disease (cSVD), a leading cause stroke and dementia with no mechanism-based treatment. We conducted genome-wide association study PSMD 58,403 participants from 24 population-based cohorts (89% European, 10% East-Asian, 1% African-American), identifying 31 independent common variant associations. Additionally,...
Brain lobar volumes are heritable but genetic studies limited. We performed genome-wide association of frontal, occipital, parietal and temporal lobe in 16,016 individuals, replicated our findings 8,789 individuals. identified six loci associated with specific independent intracranial volume. Two loci, occipital (6q22.32) volume (12q14.3), were previously reported to associate hippocampal volume, respectively. four unknown affect brain volumes: 3q24 for 1q22, 4p16.3 14q23.1 The variants...
Abstract Cortical thickness, surface area and volumes (MRI cortical measures) vary with age cognitive function, in neurological psychiatric diseases. We examined heritability, genetic correlations genome-wide associations of measures across the whole cortex, 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within Cohorts for Heart Aging Research Genomic Epidemiology (CHARGE) consortium United Kingdom Biobank. Significant were replicated...
Brain-derived neurotrophic factor (BDNF) plays an important role in brain development and function. Substantial amounts of BDNF are present peripheral blood, may serve as biomarkers for Alzheimer's disease incidence well targets intervention to reduce risk. With the exception genetic polymorphism gene, Val66Met, which has been extensively studied with regard neurodegenerative diseases, variation that influences circulating levels is unknown. We aimed explore determinants order clarify its...
Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined associations common genetic variants with verbal short-term and learning adults without dementia or stroke (N = 53,637). We identified novel loci intronic region CDH18, at 13q21 3p21.1, as well an expected signal APOE/APOC1/TOMM40 region. These results replicated independent sample. Functional bioinformatic analyses supported many these further implicated POC1. showed...
Abstract Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA UK-Biobank. show that variability subcortical is heritable, identify 25 significantly associated loci (20 novel). Annotation these utilizing gene...
Objective Multiple sclerosis (MS) is a neurological disease with substantial genetic component and immune‐mediated neurodegeneration. Patients MS show structural brain differences relative to individuals without MS, including smaller regional volumes alterations in white matter (WM) microstructure. Whether risk for associated structure during early neurodevelopment remains unclear. In this study, we explore the association between polygenic scores (PRS) imaging outcomes from large,...
Key Points Question Is the gap between brain age predicted from MRI and chronological associated with incident dementia in a general population of Dutch adults? Findings Brain was using deep learning model, MRI-derived grey matter density maps. In based study including 5496 participants, observed significantly risk dementia. Meaning The MRI-brain is potentially biomarker for screening. Abstract Importance magnetic resonance imaging (MRI) may serve as early-stage neurodegeneration indicator...