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  1. AU="van der Lee, Sven" AU="van der Lee, Sven"
  2. AU=Zani Alberto
  3. AU="Ontiveros, J Gustavo"
  4. AU="Chalifour, Matthieu"
  5. AU="Cannon, B. E."
  6. AU="Seibert, Julie"
  7. AU="Nazrul Islam"
  8. AU="Qadir, Syed Saeed"
  9. AU="Koutsoukos, Marguerite"
  10. AU="Webster, Kara"
  11. AU=Tremoulet Adriana H.
  12. AU="Foggia, Maria"
  13. AU=Eccles Michael R
  14. AU="Karrison, Theodore"
  15. AU="Espigado, I"
  16. AU="Dean, Andrew"

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Treffer 1 - 10 von insgesamt 112

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  1. Artikel ; Online: Bioinformatics Strategies for the Analysis and Integration of Large-Scale Multiomics Data.

    Tesi, Niccolo' / van der Lee, Sven / Hulsman, Marc / Holstege, Henne / Reinders, Marcel

    The journals of gerontology. Series A, Biological sciences and medical sciences

    2023  Band 78, Heft 4, Seite(n) 659–662

    Mesh-Begriff(e) Humans ; Multiomics ; Alzheimer Disease ; Computational Biology ; Genomics ; Biomarkers
    Chemische Substanzen Biomarkers
    Sprache Englisch
    Erscheinungsdatum 2023-04-03
    Erscheinungsland United States
    Dokumenttyp Editorial ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glad005
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Cognitively healthy centenarians are genetically protected against Alzheimer's disease.

    Tesi, Niccolo' / van der Lee, Sven / Hulsman, Marc / van Schoor, Natasja M / Huisman, Martijn / Pijnenburg, Yolande / van der Flier, Wiesje M / Reinders, Marcel / Holstege, Henne

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2024  

    Abstract: Background: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD.: Methods: Genome- ...

    Abstract Background: Alzheimer's disease (AD) prevalence increases with age, yet a small fraction of the population reaches ages > 100 years without cognitive decline. We studied the genetic factors associated with such resilience against AD.
    Methods: Genome-wide association studies identified 86 single nucleotide polymorphisms (SNPs) associated with AD risk. We estimated SNP frequency in 2281 AD cases, 3165 age-matched controls, and 346 cognitively healthy centenarians. We calculated a polygenic risk score (PRS) for each individual and investigated the functional properties of SNPs enriched/depleted in centenarians.
    Results: Cognitively healthy centenarians were enriched with the protective alleles of the SNPs associated with AD risk. The protective effect concentrated on the alleles in/near ANKH, GRN, TMEM106B, SORT1, PLCG2, RIN3, and APOE genes. This translated to >5-fold lower PRS in centenarians compared to AD cases (P = 7.69 × 10
    Discussion: Maintaining cognitive health until extreme ages requires complex genetic protection against AD, which concentrates on the genes associated with the endolysosomal and immune systems.
    Highlights: Cognitively healthy cent enarians are enriched with the protective alleles of genetic variants associated with Alzheimer's disease (AD). The protective effect is concentrated on variants involved in the immune and endolysosomal systems. Combining variants into a polygenic risk score (PRS) translated to > 5-fold lower PRS in centenarians compared to AD cases, and ≈ 2-fold lower compared to middle-aged healthy controls.
    Sprache Englisch
    Erscheinungsdatum 2024-04-18
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13810
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: snpXplorer: a web application to explore human SNP-associations and annotate SNP-sets.

    Tesi, Niccolo / van der Lee, Sven / Hulsman, Marc / Holstege, Henne / Reinders, Marcel J T

    Nucleic acids research

    2021  Band 49, Heft W1, Seite(n) W603–W612

    Abstract: Genetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations ... ...

    Abstract Genetic association studies are frequently used to study the genetic basis of numerous human phenotypes. However, the rapid interrogation of how well a certain genomic region associates across traits as well as the interpretation of genetic associations is often complex and requires the integration of multiple sources of annotation, which involves advanced bioinformatic skills. We developed snpXplorer, an easy-to-use web-server application for exploring Single Nucleotide Polymorphisms (SNP) association statistics and to functionally annotate sets of SNPs. snpXplorer can superimpose association statistics from multiple studies, and displays regional information including SNP associations, structural variations, recombination rates, eQTL, linkage disequilibrium patterns, genes and gene-expressions per tissue. By overlaying multiple GWAS studies, snpXplorer can be used to compare levels of association across different traits, which may help the interpretation of variant consequences. Given a list of SNPs, snpXplorer can also be used to perform variant-to-gene mapping and gene-set enrichment analysis to identify molecular pathways that are overrepresented in the list of input SNPs. snpXplorer is freely available at https://snpxplorer.net. Source code, documentation, example files and tutorial videos are available within the Help section of snpXplorer and at https://github.com/TesiNicco/snpXplorer.
    Mesh-Begriff(e) Alzheimer Disease/genetics ; Gene Expression ; Genetic Association Studies ; Genomics ; Humans ; Linkage Disequilibrium ; Molecular Sequence Annotation ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Software
    Sprache Englisch
    Erscheinungsdatum 2021-05-28
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 186809-3
    ISSN 1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
    ISSN (online) 1362-4962 ; 1362-4954
    ISSN 0301-5610 ; 0305-1048
    DOI 10.1093/nar/gkab410
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Interest in genetic susceptibility testing and disclosure of AD dementia risk in cognitively normal adults: a survey study.

    Waterink, Lisa / Masselink, Larissa A / van der Lee, Sven J / Visser, Leonie N C / Cleutjens, Solange / van der Schaar, Jetske / van Harten, Argonde C / Scheltens, Philip / Sikkes, Sietske A M / van der Flier, Wiesje M / Zwan, Marissa D

    Alzheimer's research & therapy

    2024  Band 16, Heft 1, Seite(n) 1

    Abstract: Background: Apolipoprotein-E (APOE) genetic testing for Alzheimer's disease is becoming more important as clinical trials are increasingly targeting individuals carrying APOE-ε4 alleles. Little is known about the interest in finding out one's genetic ... ...

    Abstract Background: Apolipoprotein-E (APOE) genetic testing for Alzheimer's disease is becoming more important as clinical trials are increasingly targeting individuals carrying APOE-ε4 alleles. Little is known about the interest in finding out one's genetic risk for Alzheimer's disease in the general population. Our objective was to examine this in a sample of cognitively normal (CN) adults within a population-based online research registry with the goal to implement APOE-ε4 status for trial recruitment.
    Methods: An online survey was completed by 442 CN participants between the age of 49 and 75 years (56% female) from the Dutch Brain Research Registry. The survey assessed interest in participation in research into, and disclosure of, genetic risk for dementia. The survey assessed interest in participation in research into, and disclosure of, genetic risk for dementia and knowing their genetic risk in different hypothetical risk scenarios (10%, 30%, and 50% genetic risk for dementia at age 85, corresponding to APOEε2/ε2 or ε2/ε3, APOEε3/ε4 or ε2ε4, and APOE-ε4/ε4 genotypes). Cochran's Q and post hoc McNemar tests were used to analyse differences in frequencies across scenarios.
    Results: Most participants were interested in participating in research into and disclosure of their genetic risk (81%). The most reported reason was to contribute to scientific research (94%). Interest was higher in males, whilst lower-educated participants were more often undecided. When provided with different risk scenarios, interest in knowing their risk was somewhat higher in the scenarios with higher risk, i.e. in the 50% (79%) compared to the 10% scenario (73%;χ
    Conclusions: Our findings indicate that the vast majority of CN adults participating in a research registry expresses interest in AD genetic risk research and disclosure. Interest in genetic risk disclosure is higher in scenarios corresponding to the APOE-ε4 genotype. This suggests APOE-ε4 screening within an online research registry is potentially a well-received method to accelerate inclusion for trials.
    Mesh-Begriff(e) Male ; Adult ; Humans ; Female ; Middle Aged ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Alzheimer Disease/genetics ; Alzheimer Disease/epidemiology ; Disclosure ; Genotype ; Apolipoproteins E/genetics ; Genetic Predisposition to Disease/genetics ; Apolipoprotein E4/genetics
    Chemische Substanzen Apolipoproteins E ; Apolipoprotein E4
    Sprache Englisch
    Erscheinungsdatum 2024-01-02
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2506521-X
    ISSN 1758-9193 ; 1758-9193
    ISSN (online) 1758-9193
    ISSN 1758-9193
    DOI 10.1186/s13195-023-01364-w
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review.

    Kwetsie, Hadassa / van Schaijk, Malu / Van Der Lee, Sven / Maes-Festen, Dederieke / Ten Hoopen, Leontine W / van Haelst, Mieke M / Coesmans, Michael / Van Den Berg, Esther / De Wit, Marie Claire Y / Pijnenburg, Yolande / Aronica, Eleonora / Boot, Erik / Van Eeghen, Agnies M

    Neurology

    2024  Band 102, Heft 11, Seite(n) e209413

    Abstract: Background and objectives: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a ... ...

    Abstract Background and objectives: Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs.
    Methods: A systematic literature review was conducted in Embase, Medline ALL, and PsycINFO on December 6, 2022. The protocol was registered in PROSPERO (CRD42021223041). Search terms for dementia, cognitive and adaptive functioning, and RGNDs were combined using generic terms and the Orphanet database. Study characteristics and descriptive data on genetic diagnosis, clinical and neuropathologic features, comorbidities, and diagnostic methods were extracted using a modified version of the Cochrane Data Extraction Template.
    Results: The literature search yielded 40 publications (17 cohorts, 23 case studies) describing dementia and/or cognitive or adaptive trajectories in adults with 14 different RGNDs. Dementia was reported in 49 individuals (5 cohorts, 20 cases) with a mean age at onset of 44.4 years. Diagnostics were not disclosed for half of the reported individuals (n = 25/49, 51.0%). A total of 44 different psychodiagnostic instruments were used. MRI was the most reported additional investigation (n = 12/49, 24.5%). Comorbid disorders most frequently associated with cognitive/adaptive decline were epilepsy, psychotic disorders, and movement disorders.
    Discussion: Currently available literature shows limited information on aging in RGNDs, with relatively many reports of young-onset dementia. Longitudinal data may provide insights into converging neurodevelopmental degenerative pathways. We provide recommendations to optimize dementia screening, diagnosis, and research.
    Mesh-Begriff(e) Humans ; Dementia/genetics ; Dementia/epidemiology ; Dementia/diagnosis ; Neurodevelopmental Disorders/genetics ; Neurodevelopmental Disorders/diagnosis ; Rare Diseases/genetics ; Adult
    Sprache Englisch
    Erscheinungsdatum 2024-05-17
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Systematic Review
    ZDB-ID 207147-2
    ISSN 1526-632X ; 0028-3878
    ISSN (online) 1526-632X
    ISSN 0028-3878
    DOI 10.1212/WNL.0000000000209413
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: The Role of Age-Related Clonal Hematopoiesis in Genetic Sequencing Studies.

    Holstege, Henne / Hulsman, Marc / van der Lee, Sven J / van den Akker, Erik B

    American journal of human genetics

    2020  Band 107, Heft 3, Seite(n) 575–576

    Mesh-Begriff(e) DNA-Binding Proteins ; Dioxygenases ; Hematopoiesis ; High-Throughput Nucleotide Sequencing ; Humans ; Neurodegenerative Diseases ; Proto-Oncogene Proteins
    Chemische Substanzen DNA-Binding Proteins ; Proto-Oncogene Proteins ; Dioxygenases (EC 1.13.11.-) ; TET2 protein, human (EC 1.13.11.-)
    Sprache Englisch
    Erscheinungsdatum 2020-08-08
    Erscheinungsland United States
    Dokumenttyp Letter ; Comment
    ZDB-ID 219384-x
    ISSN 1537-6605 ; 0002-9297
    ISSN (online) 1537-6605
    ISSN 0002-9297
    DOI 10.1016/j.ajhg.2020.07.011
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Cerebrospinal fluid proteomics in patients with Alzheimer's disease reveals five molecular subtypes with distinct genetic risk profiles.

    Tijms, Betty M / Vromen, Ellen M / Mjaavatten, Olav / Holstege, Henne / Reus, Lianne M / van der Lee, Sven / Wesenhagen, Kirsten E J / Lorenzini, Luigi / Vermunt, Lisa / Venkatraghavan, Vikram / Tesi, Niccoló / Tomassen, Jori / den Braber, Anouk / Goossens, Julie / Vanmechelen, Eugeen / Barkhof, Frederik / Pijnenburg, Yolande A L / van der Flier, Wiesje M / Teunissen, Charlotte E /
    Berven, Frode S / Visser, Pieter Jelle

    Nature aging

    2024  Band 4, Heft 1, Seite(n) 33–47

    Abstract: Alzheimer's disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, ...

    Abstract Alzheimer's disease (AD) is heterogenous at the molecular level. Understanding this heterogeneity is critical for AD drug development. Here we define AD molecular subtypes using mass spectrometry proteomics in cerebrospinal fluid, based on 1,058 proteins, with different levels in individuals with AD (n = 419) compared to controls (n = 187). These AD subtypes had alterations in protein levels that were associated with distinct molecular processes: subtype 1 was characterized by proteins related to neuronal hyperplasticity; subtype 2 by innate immune activation; subtype 3 by RNA dysregulation; subtype 4 by choroid plexus dysfunction; and subtype 5 by blood-brain barrier impairment. Each subtype was related to specific AD genetic risk variants, for example, subtype 1 was enriched with TREM2 R47H. Subtypes also differed in clinical outcomes, survival times and anatomical patterns of brain atrophy. These results indicate molecular heterogeneity in AD and highlight the need for personalized medicine.
    Mesh-Begriff(e) Humans ; Alzheimer Disease/genetics ; Proteomics
    Sprache Englisch
    Erscheinungsdatum 2024-01-09
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 2662-8465
    ISSN (online) 2662-8465
    DOI 10.1038/s43587-023-00550-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: What does heritability of Alzheimer's disease represent?

    Baker, Emily / Leonenko, Ganna / Schmidt, Karl Michael / Hill, Matthew / Myers, Amanda J / Shoai, Maryam / de Rojas, Itziar / Tesi, Niccoló / Holstege, Henne / van der Flier, Wiesje M / Pijnenburg, Yolande A L / Ruiz, Agustin / Hardy, John / van der Lee, Sven / Escott-Price, Valentina

    PloS one

    2023  Band 18, Heft 4, Seite(n) e0281440

    Abstract: Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the ... ...

    Abstract Introduction: Both late-onset Alzheimer's disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability.
    Methods: We compute heritability in five large independent cohorts (N = 7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set.
    Results: SNP-based heritability of late onset Alzheimer's disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD = 8%] on average when the APOE region is excluded and an additional 1% [SD = 3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts.
    Conclusion: The heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.
    Mesh-Begriff(e) Humans ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Alzheimer Disease/genetics ; Genetic Loci ; Polymorphism, Single Nucleotide ; Apolipoproteins E/genetics
    Chemische Substanzen Apolipoproteins E
    Sprache Englisch
    Erscheinungsdatum 2023-04-28
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0281440
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel: Quantitative trait loci mapping of circulating metabolites in cerebrospinal fluid to uncover biological mechanisms involved in brain-related phenotypes.

    Reus, Lianne M / Boltz, Toni / Francia, Marcelo / Bot, Merel / Ramesh, Naren / Koromina, Maria / Pijnenburg, Yolande A L / den Braber, Anouk / van der Flier, Wiesje M / Visser, Pieter Jelle / van der Lee, Sven J / Tijms, Betty M / Teunissen, Charlotte E / Loohuis, Loes Olde / Ophoff, Roel A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Genomic studies of molecular traits have provided mechanistic insights into complex disease, though these lag behind for brain-related traits due to the inaccessibility of brain tissue. We leveraged cerebrospinal fluid (CSF) to study neurobiological ... ...

    Abstract Genomic studies of molecular traits have provided mechanistic insights into complex disease, though these lag behind for brain-related traits due to the inaccessibility of brain tissue. We leveraged cerebrospinal fluid (CSF) to study neurobiological mechanisms
    Sprache Englisch
    Erscheinungsdatum 2023-09-27
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.09.26.559021
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  10. Artikel ; Online: Association of MGMT and BIN1 genes with Alzheimer's disease risk across sex and APOE ε4 status.

    Le Borgne, Julie / Amouyel, Philippe / Andreassen, Ole / Frikke-Schmidt, Ruth / Hiltunen, Mikko / Ingelsson, Martin / Ramirez, Alfredo / Rossi, Giacomina / Ruiz, Agustin / Sanchez-Juan, Pascual / Sims, Rebecca / Sleegers, Kristel / Tsolaki, Magda / van der Lee, Sven J / Williams, Julie / Lambert, Jean-Charles / Bellenguez, Céline

    Alzheimer's & dementia : the journal of the Alzheimer's Association

    2023  Band 20, Heft 3, Seite(n) 2282–2284

    Mesh-Begriff(e) Humans ; Apolipoprotein E4/genetics ; Alzheimer Disease/genetics ; Apolipoproteins E/genetics ; Nuclear Proteins/genetics ; Tumor Suppressor Proteins/genetics ; Adaptor Proteins, Signal Transducing/genetics ; DNA Modification Methylases ; DNA Repair Enzymes
    Chemische Substanzen Apolipoprotein E4 ; Apolipoproteins E ; BIN1 protein, human ; Nuclear Proteins ; Tumor Suppressor Proteins ; Adaptor Proteins, Signal Transducing ; MGMT protein, human (EC 2.1.1.63) ; DNA Modification Methylases (EC 2.1.1.-) ; DNA Repair Enzymes (EC 6.5.1.-)
    Sprache Englisch
    Erscheinungsdatum 2023-12-02
    Erscheinungsland United States
    Dokumenttyp Letter
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13550
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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