Sven J. van der Lee
- Genetic Associations and Epidemiology
- Alzheimer's disease research and treatments
- Bioinformatics and Genomic Networks
- Dementia and Cognitive Impairment Research
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Neuroinflammation and Neurodegeneration Mechanisms
- Nutrition, Genetics, and Disease
- Metabolomics and Mass Spectrometry Studies
- Health, Environment, Cognitive Aging
- Epigenetics and DNA Methylation
- Folate and B Vitamins Research
- Neurological diseases and metabolism
- Prion Diseases and Protein Misfolding
- Diet and metabolism studies
- Machine Learning in Bioinformatics
- Amyotrophic Lateral Sclerosis Research
- Biological Research and Disease Studies
- Genetics, Aging, and Longevity in Model Organisms
- Tryptophan and brain disorders
- Genomics and Phylogenetic Studies
- Genomic variations and chromosomal abnormalities
- Liver Disease Diagnosis and Treatment
- Mitochondrial Function and Pathology
- Functional Brain Connectivity Studies
Vrije Universiteit Amsterdam
2017-2025
Amsterdam University Medical Centers
2017-2025
Amsterdam Neuroscience
2017-2025
Delft University of Technology
2020-2024
University of Amsterdam
2019-2024
Trimbos Institute
2024
's Heeren Loo
2024
Erasmus MC
2013-2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2018-2022
Medical University of Graz
2022
Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified genetic sharing 25 disorders from genome-wide association studies 265,218 patients 784,643 control participants assessed relationship to 17 phenotypes 1,191,588 individuals. Psychiatric common variant risk, whereas neurological appear more distinct one another psychiatric disorders. also identified significant between a number...
Abstract Characterization of the genetic landscape Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for better understanding associated pathophysiological processes. We performed two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases 677,663 controls. found 75 risk loci, which 42 were new at time analysis. Pathway enrichment analyses confirmed involvement amyloid/tau pathways highlighted microglia implication. Gene...
Abstract We conduct a genome-wide association study (GWAS) of educational attainment (EA) in sample ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A polygenic predictor, or index (PGI), explains 12–16% EA variance contributes to risk prediction for ten diseases. Direct effects (i.e., controlling parental PGIs) explain roughly half the PGI’s magnitude with other phenotypes. The correlation between mate-pair...
Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic...
Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for therapeutic strategy disease.
The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 177 were Caribbean Hispanic (CH). An age-, sex- APOE based risk score family history used to select most likely harbor novel AD variants least develop by age 85 years. We tested ~1.5 million single nucleotide (SNVs) 50,000 insertion-deletion polymorphisms (indels) for...
Abstract Introduction Metabolite, lipid, and lipoprotein lipid profiling can provide novel insights into mechanisms underlying incident dementia Alzheimer's disease. Methods We studied eight prospective cohorts with 22,623 participants profiled by nuclear magnetic resonance or mass spectrometry metabolomics. Four were used for discovery replication undertaken in the other four to avoid false positives. For metabolites that survived replication, combined association results are presented....
Abstract Introduction Identifying circulating metabolites that are associated with cognition and dementia may improve our understanding of the pathogenesis provide crucial readouts for preventive therapeutic interventions. Methods We studied 299 in relation to (general cognitive ability) two discovery cohorts (N total = 5658). Metabolites significantly after adjusting multiple testing were replicated four independent 6652), associations Alzheimer's disease 25,872) lifestyle factors 5168)...
Abstract Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability approximately 70% 1 . The genetic component AD been mainly assessed using genome-wide association studies, which do not capture risk contributed by rare variants 2 Here, we compared gene-based burden damaging in exome sequencing data from 32,558 individuals—16,036 cases and 16,522 controls. Next to TREM2 , SORL1 ABCA7 observed a significant rare, predicted ATP8B4 ABCA1 with risk, suggestive signal...
Abstract Alzheimer’s disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity critical for AD drug development. Here we define subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels individuals ( n = 419) compared to controls 187). These had alterations protein that were associated distinct processes: subtype 1 was characterized by proteins related neuronal hyperplasticity; 2 innate immune activation; 3...
Importance An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most these lacking. Effective interventions should target in causal pathway to dementia. Objective To comprehensively disentangle aspects modifiable Alzheimer disease (AD) inspire new drug targeting and improved prevention. Design, Setting, Participants This genetic association study was conducted using 2-sample univariable multivariable...