Iris E. Jansen
A5046044622- Alzheimer's disease research and treatments
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Parkinson's Disease Mechanisms and Treatments
- Genomics and Rare Diseases
- Health, Environment, Cognitive Aging
- Dementia and Cognitive Impairment Research
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological diseases and metabolism
- Genetics and Neurodevelopmental Disorders
- Machine Learning in Bioinformatics
- Nutrition, Genetics, and Disease
- Gene expression and cancer classification
- Lysosomal Storage Disorders Research
- Autism Spectrum Disorder Research
- Genetic Neurodegenerative Diseases
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- Neurogenetic and Muscular Disorders Research
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Receptors and Signaling
- CRISPR and Genetic Engineering
- Congenital heart defects research
GlaxoSmithKline (Belgium)
2025
Amsterdam Neuroscience
2016-2024
Amsterdam University Medical Centers
2018-2024
Vrije Universiteit Amsterdam
2013-2024
Cognitive Research (United States)
2024
Molecular Biology Consortium
2023
Amsterdam UMC Location VUmc
2011-2022
Delft University of Technology
2021
German Center for Neurodegenerative Diseases
2015-2020
University Hospital Bonn
2020
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...
Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants other lysosomal storage disorder genes is more broadly associated with disease susceptibility. The sequence kernel association test was used to interrogate variant among 54 genes, leveraging whole exome sequencing data from 1156 cases and 1679 control subjects. discovered significant rare, likely damaging risk....
Recent genome-wide association studies (GWAS) and pathway analyses supported long-standing observations of an between immune-mediated diseases Parkinson disease (PD). The post-GWAS era provides opportunity for cross-phenotype different complex phenotypes.To test the hypothesis that there are common genetic risk variants conveying both PD autoimmune (ie, pleiotropy) to identify new shared their pathways by applying a novel statistical framework in approach.Using conjunction false discovery...
We hypothesized that specific mutations in the β-glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) homozygotes lead to aggressive cognitive decline heterozygous Parkinson's (PD) patients, whereas non-neuropathic GD confer intermediate progression rates.
Genetic discoveries of Alzheimer's disease are the drivers our understanding, and together with polygenetic risk stratification can contribute towards planning feasible efficient preventive curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets by-proxy results (discovery n = 409,435 validation size 58,190). Here, we add six variants associated (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 two exonic in SHARPIN gene). Assessment...
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...
Alzheimer's disease is biologically heterogeneous, and detailed understanding of the processes involved in patients critical for development treatments. CSF contains hundreds proteins, with concentrations reflecting ongoing (patho)physiological processes. This provides opportunity to study many biological at same time patients. We studied whether subtypes can be detected proteomics using dual clustering technique non-negative matrix factorization. In two independent cohorts (EMIF-AD MBD...
The genetic variant rs72824905-G (minor allele) in the PLCG2 gene was previously associated with a reduced Alzheimer's disease risk (AD). role of immune system signaling suggests it may also protect against other neurodegenerative diseases and possibly associates longevity. We studied effect on seven longevity, using 53,627 patients, 3,516 long-lived individuals 149,290 study-matched controls. replicated association AD we found an dementia Lewy bodies (DLB) frontotemporal (FTD). did not find...
Whole-exome sequencing (WES) has been successful in identifying genes that cause familial Parkinson's disease (PD). However, until now this approach not deployed to study large cohorts of unrelated participants. To discover rare PD susceptibility variants, we performed WES 1148 cases and 503 control Candidate were subsequently validated for functions relevant based on parallel RNA-interference (RNAi) screens human cell culture Drosophila C. elegans models. Assuming autosomal recessive...
ABSTRACT Alzheimer’s disease (AD) is a severe and incurable neurodegenerative disease, the failure to find effective treatments suggests that underlying pathology remains poorly understood. Due its strong heritability, deciphering genetic landscape of AD related dementia (ADD) unique opportunity advance our knowledge. We completed meta-analysis genome-wide association studies (39,106 clinically AD-diagnosed cases, 46,828 proxy-ADD cases 401,577 controls) with most promising signals...
Abstract Background Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer’s disease (AD) and considered to result from neurodegeneration. T-tau levels, however, can be increased very early stages, when neurodegeneration limited, normal advanced stages. This suggests that t-tau levels may driven by other mechanisms as well. Because pathophysiology emerging treatment target for AD, we aimed clarify molecular processes associated with CSF levels. Methods...
The APOE ε2 and ε4 alleles are the strongest protective risk-increasing, respectively, genetic variants for late-onset Alzheimer disease (AD). However, mechanisms linking to AD-particularly apoE protein's role in AD pathogenesis how this is affected by variants-remain poorly understood. Identifying missense addition could provide critical new insights, but given low frequency of additional variants, cohorts have previously been too small interrogate question robustly.To determine whether...
PurposeTo define the genetic spectrum and relative gene frequencies underlying clinical frontotemporal dementia (FTD).MethodsWe investigated mutations in neurodegenerative disease genes 121 consecutive FTD subjects using an unbiased, combined sequencing approach, complemented by cerebrospinal fluid Aβ1-42 serum progranulin measurements. Subjects were screened for C9orf72 repeat expansions, GRN MAPT mutations, and, if negative, other genes, whole-exome (WES) (n = 108), including WES-based...
Abstract A rare coding variant (rs72824905, p.P522R) conferring protection against Alzheimer’s disease (AD) was identified in the gene encoding enzyme phospholipase-C-γ2 ( PLCG2 ) that is highly expressed microglia. To explore protective nature of this variant, we employed latent process linear mixed models to examine association p.P522R with longitudinal cognitive decline 3595 MCI patients, and 10,097 individuals from population-based studies. Furthermore, CSF levels pTau 181 , total tau,...
A quarter of the world’s population is estimated to meet criteria for metabolic syndrome (MetS), a cluster cardiometabolic risk factors that promote development coronary artery disease and type 2 diabetes, leading increased premature death significant health costs. In this study we investigate whether genetics associated with MetS components mirror their phenotypic clustering. multivariate approach leverages genetic correlations fasting glucose, HDL cholesterol, systolic blood pressure,...