LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 65

Search options

  1. Article ; Online: Step by step: towards a better understanding of the genetic architecture of Alzheimer's disease.

    Lambert, Jean-Charles / Ramirez, Alfredo / Grenier-Boley, Benjamin / Bellenguez, Céline

    Molecular psychiatry

    2023  Volume 28, Issue 7, Page(s) 2716–2727

    Abstract: Alzheimer's disease (AD) is considered to have a large genetic component. Our knowledge of this component has progressed over the last 10 years, thanks notably to the advent of genome-wide association studies and the establishment of large consortia that ...

    Abstract Alzheimer's disease (AD) is considered to have a large genetic component. Our knowledge of this component has progressed over the last 10 years, thanks notably to the advent of genome-wide association studies and the establishment of large consortia that make it possible to analyze hundreds of thousands of cases and controls. The characterization of dozens of chromosomal regions associated with the risk of developing AD and (in some loci) the causal genes responsible for the observed disease signal has confirmed the involvement of major pathophysiological pathways (such as amyloid precursor protein metabolism) and opened up new perspectives (such as the central role of microglia and inflammation). Furthermore, large-scale sequencing projects are starting to reveal the major impact of rare variants - even in genes like APOE - on the AD risk. This increasingly comprehensive knowledge is now being disseminated through translational research; in particular, the development of genetic risk/polygenic risk scores is helping to identify the subpopulations more at risk or less at risk of developing AD. Although it is difficult to assess the efforts still needed to comprehensively characterize the genetic component of AD, several lines of research can be improved or initiated. Ultimately, genetics (in combination with other biomarkers) might help to redefine the boundaries and relationships between various neurodegenerative diseases.
    MeSH term(s) Humans ; Alzheimer Disease/genetics ; Genome-Wide Association Study ; Risk Factors ; Biomarkers ; Apolipoproteins E/genetics
    Chemical Substances Biomarkers ; Apolipoproteins E
    Language English
    Publishing date 2023-05-02
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1330655-8
    ISSN 1476-5578 ; 1359-4184
    ISSN (online) 1476-5578
    ISSN 1359-4184
    DOI 10.1038/s41380-023-02076-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 4812: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  2. Article ; Online: Genetics of Alzheimer's disease: where we are, and where we are going.

    Bellenguez, Céline / Grenier-Boley, Benjamin / Lambert, Jean-Charles

    Current opinion in neurobiology

    2019  Volume 61, Page(s) 40–48

    Abstract: Alzheimer's disease (AD) has a very strong genetic component, whose characterization has become an essential part of efforts to understand the pathophysiological processes of the disease. Thanks to the systematic use of high-throughput approaches over ... ...

    Abstract Alzheimer's disease (AD) has a very strong genetic component, whose characterization has become an essential part of efforts to understand the pathophysiological processes of the disease. Thanks to the systematic use of high-throughput approaches over the last 10 years, more than 40 genes/loci have been linked to the AD risk. Although some of these signals are likely to be false positives, this genetic knowledge has shed new light on the pathogenesis of AD and, in particular, the major role of microglia. However, our knowledge of the genetics of AD is far from complete, and larger and more diverse genetic studies are required. Lastly, post-GWAS analyses will be needed to make sense of this genetic information without focusing too much on what we think we know about the disease.
    MeSH term(s) Alzheimer Disease ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Microglia
    Language English
    Publishing date 2019-12-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1078046-4
    ISSN 1873-6882 ; 0959-4388
    ISSN (online) 1873-6882
    ISSN 0959-4388
    DOI 10.1016/j.conb.2019.11.024
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3260: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: Genetics of PlGF plasma levels highlights a role of its receptors and supports the link between angiogenesis and immunity.

    Ruggiero, Daniela / Nutile, Teresa / Nappo, Stefania / Tirozzi, Alfonsina / Bellenguez, Celine / Leutenegger, Anne-Louise / Ciullo, Marina

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 16821

    Abstract: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several ... ...

    Abstract Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is involved in bone marrow-derived cell activation, endothelial stimulation and pathological angiogenesis. High levels of PlGF have been observed in several pathological conditions especially in cancer, cardiovascular, autoimmune and inflammatory diseases. Little is known about the genetics of circulating PlGF levels. Indeed, although the heritability of circulating PlGF levels is around 40%, no studies have assessed the relation between PlGF plasma levels and genetic variants at a genome-wide level. In the current study, PlGF plasma levels were measured in a population-based sample of 2085 adult individuals from three isolated populations of South Italy. A GWAS was performed in a discovery cohort (N = 1600), followed by a de novo replication (N = 468) from the same populations. The meta-analysis of the discovery and replication samples revealed one signal significantly associated with PlGF circulating levels. This signal was mapped to the PlGF co-receptor coding gene NRP1, indicating its important role in modulating the PlGF plasma levels. Two additional signals, at the PlGF receptor coding gene FLT1 and RAPGEF5 gene, were identified at a suggestive level. Pathway and TWAS analyses highlighted genes known to be involved in angiogenesis and immune response, supporting the link between these processes and PlGF regulation. Overall, these data improve our understanding of the genetic variation underlying circulating PlGF levels. This in turn could lead to new preventive and therapeutic strategies for a wide variety of PlGF-related pathologies.
    MeSH term(s) Adult ; Cohort Studies ; Female ; Genome-Wide Association Study ; Humans ; Immunity/genetics ; Male ; Meta-Analysis as Topic ; Middle Aged ; Neovascularization, Physiologic/genetics ; Placenta Growth Factor/blood ; Reproducibility of Results ; Signal Transduction/genetics ; Transcription, Genetic
    Chemical Substances Placenta Growth Factor (144589-93-5)
    Language English
    Publishing date 2021-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-96256-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; 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  Volume 20, Issue 3, Page(s) 2282–2284

    MeSH term(s) 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
    Chemical Substances 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.-)
    Language English
    Publishing date 2023-12-02
    Publishing country United States
    Document type Letter
    ZDB-ID 2211627-8
    ISSN 1552-5279 ; 1552-5260
    ISSN (online) 1552-5279
    ISSN 1552-5260
    DOI 10.1002/alz.13550
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 6316: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 540: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  5. Article ; Online: Strategies for phasing and imputation in a population isolate.

    Herzig, Anthony Francis / Nutile, Teresa / Babron, Marie-Claude / Ciullo, Marina / Bellenguez, Céline / Leutenegger, Anne-Louise

    Genetic epidemiology

    2018  Volume 42, Issue 2, Page(s) 201–213

    Abstract: In the search for genetic associations with complex traits, population isolates offer the advantage of reduced genetic and environmental heterogeneity. In addition, cost-efficient next-generation association approaches have been proposed in these ... ...

    Abstract In the search for genetic associations with complex traits, population isolates offer the advantage of reduced genetic and environmental heterogeneity. In addition, cost-efficient next-generation association approaches have been proposed in these populations where only a subsample of representative individuals is sequenced and then genotypes are imputed into the rest of the population. Gene mapping in such populations thus requires high-quality genetic imputation and preliminary phasing. To identify an effective study design, we compare by simulation a range of phasing and imputation software and strategies. We simulated 1,115,604 variants on chromosome 10 for 477 members of the large complex pedigree of Campora, a village within the established isolate of Cilento in southern Italy. We assessed the phasing performance of identical by descent based software ALPHAPHASE and SLRP, LD-based software SHAPEIT2, SHAPEIT3, and BEAGLE, and new software EAGLE that combines both methodologies. For imputation we compared IMPUTE2, IMPUTE4, MINIMAC3, BEAGLE, and new software PBWT. Genotyping errors and missing genotypes were simulated to observe their effects on the performance of each software. Highly accurate phased data were achieved by all software with SHAPEIT2, SHAPEIT3, and EAGLE2 providing the most accurate results. MINIMAC3, IMPUTE4, and IMPUTE2 all performed strongly as imputation software and our study highlights the considerable gain in imputation accuracy provided by a genome sequenced reference panel specific to the population isolate.
    MeSH term(s) Algorithms ; Chromosomes, Human, Pair 10/genetics ; Female ; Founder Effect ; Genetics, Population ; Genome, Human/genetics ; Haplotypes/genetics ; Humans ; Italy ; Linkage Disequilibrium/genetics ; Male ; Models, Genetic ; Pedigree ; Phenotype ; Research Design ; Software
    Language English
    Publishing date 2018
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 605785-8
    ISSN 1098-2272 ; 0741-0395
    ISSN (online) 1098-2272
    ISSN 0741-0395
    DOI 10.1002/gepi.22109
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1969: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  6. Article ; Online: Accuracy of heritability estimations in presence of hidden population stratification.

    Dandine-Roulland, Claire / Bellenguez, Céline / Debette, Stéphanie / Amouyel, Philippe / Génin, Emmanuelle / Perdry, Hervé

    Scientific reports

    2016  Volume 6, Page(s) 26471

    Abstract: The heritability of a trait is the proportion of its variance explained by genetic factors; it has historically been estimated using familial data. However, new methods have appeared for estimating heritabilities using genomewide data from unrelated ... ...

    Abstract The heritability of a trait is the proportion of its variance explained by genetic factors; it has historically been estimated using familial data. However, new methods have appeared for estimating heritabilities using genomewide data from unrelated individuals. A drawback of this strategy is that population stratification can bias the estimates. Indeed, an environmental factor associated with the phenotype may differ among population subgroups. This factor being associated both with the phenotype and the genetic variation in the population would be a confounder. A common solution consists in adjusting on the first Principal Components (PCs) of the genomic data. We study this procedure on simulated data and on 6000 individuals from the Three-City Study. We analyse the geographical coordinates of the birth cities, which are not genetically determined, but the heritability of which should be overestimated due to population stratification. We also analyse various anthropometric traits. The procedure fails to correct the bias in geographical coordinates heritability estimates. The heritability estimates of the anthropometric traits are affected by the inclusion of the first PC, but not by the following PCs, contrarily to geographical coordinates. We recommend to be cautious with heritability estimates obtained from a large population.
    Language English
    Publishing date 2016-05-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/srep26471
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  7. Article ; Online: A multiple splitting approach to linkage analysis in large pedigrees identifies a linkage to asthma on chromosome 12.

    Bellenguez, Céline / Ober, Carole / Bourgain, Catherine

    Genetic epidemiology

    2009  Volume 33, Issue 3, Page(s) 207–216

    Abstract: Large genealogies are potentially very informative for linkage analysis. However, the software available for exact non-parametric multipoint linkage analysis is limited with respect to the complexity of the families it can handle. A solution is to split ... ...

    Abstract Large genealogies are potentially very informative for linkage analysis. However, the software available for exact non-parametric multipoint linkage analysis is limited with respect to the complexity of the families it can handle. A solution is to split the large pedigrees into sub-families meeting complexity constraints. Different methods have been proposed to "best" split large genealogies. Here, we propose a new procedure in which linkage is performed on several carefully chosen sub-pedigree sets from the genealogy instead of using just a single sub-pedigree set. Our multiple splitting procedure capitalizes on the sensitivity of linkage results to family structure and has been designed to control computational feasibility and global type I error. We describe and apply this procedure to the extreme case of the highly complex Hutterite pedigree and use it to perform a genome-wide linkage analysis on asthma. The detection of a genome-wide significant linkage for asthma on chromosome 12q21 illustrates the potential of this multiple splitting approach.
    MeSH term(s) Asthma/genetics ; Chromosomes, Human, Pair 12/genetics ; Computational Biology/methods ; Genetic Linkage ; Humans ; Pedigree
    Language English
    Publishing date 2009-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 605785-8
    ISSN 1098-2272 ; 0741-0395
    ISSN (online) 1098-2272
    ISSN 0741-0395
    DOI 10.1002/gepi.20371
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1969: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  8. Article ; Online: Linkage analysis with dense SNP maps in isolated populations.

    Bellenguez, Céline / Ober, Carole / Bourgain, Catherine

    Human heredity

    2009  Volume 68, Issue 2, Page(s) 87–97

    Abstract: Objective: SNP maps are becoming the gold standard for genetic markers, even for linkage analyses. However, because of the density of SNPs on most high throughput platforms, the resulting significant linkage disequilibrium (LD) can bias classical ... ...

    Abstract Objective: SNP maps are becoming the gold standard for genetic markers, even for linkage analyses. However, because of the density of SNPs on most high throughput platforms, the resulting significant linkage disequilibrium (LD) can bias classical nonparametric multipoint linkage analyses. This problem may be even stronger in population isolates where LD can extend over larger distances and with a more stochastic pattern. We investigate the issue of linkage analysis with SNPs from the Affymetrix 500K GeneChip array in extended families from the isolated Hutterite population.
    Methods: We minimized LD between SNPs by two methods based on a LD block pattern (Merlin and SNPLINK) and by MASEL, a new algorithm that we proposed to select SNP subsets with minimum LD and with no prior hypothesis about the LD pattern.
    Results: Simulations, performed using the real LD pattern observed in the Hutterite population, show that sizeable inflation of linkage statistics persist when LD between SNPs is minimized by Merlin and SNPLINK. Inflation of linkage statistics is better controlled with MASEL.
    Conclusion: In this population, it may be difficult to extract from standard GeneChip arrays a SNP map without LD-driven bias that is more informative than a dense microsatellite map.
    MeSH term(s) Algorithms ; Genetic Linkage ; Humans ; Polymorphism, Single Nucleotide ; Protestantism ; Social Isolation
    Language English
    Publishing date 2009-04-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2424-7
    ISSN 1423-0062 ; 0001-5652
    ISSN (online) 1423-0062
    ISSN 0001-5652
    DOI 10.1159/000212501
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Un I Zs.466: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  9. Article ; Online: PLD3 and sporadic Alzheimer's disease risk.

    Lambert, Jean-Charles / Grenier-Boley, Benjamin / Bellenguez, Céline / Pasquier, Florence / Campion, Dominique / Dartigues, Jean-Francois / Berr, Claudine / Tzourio, Christophe / Amouyel, Philippe

    Nature

    2015  Volume 520, Issue 7545, Page(s) E1

    MeSH term(s) Alzheimer Disease/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Genetic Variation/genetics ; Humans ; Male ; Phospholipase D/genetics
    Chemical Substances Phospholipase D (EC 3.1.4.4)
    Language English
    Publishing date 2015-04-02
    Publishing country England
    Document type Comment ; Letter
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/nature14036
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 26: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 9: Show issues
    Zs.MO 244: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  10. Article ; Online: The role of ATM in response to metformin treatment and activation of AMPK.

    Zhou, Kaixin / Bellenguez, Celine / Sutherland, Calum / Hardie, Grahame / Palmer, Colin / Donnelly, Peter / Pearson, Ewan

    Nature genetics

    2012  Volume 44, Issue 4, Page(s) 361–362

    MeSH term(s) Animals ; Cell Cycle Proteins/genetics ; DNA-Binding Proteins/genetics ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/genetics ; Humans ; Metformin/pharmacology ; Protein-Serine-Threonine Kinases/genetics ; Tumor Suppressor Proteins/genetics
    Chemical Substances Cell Cycle Proteins ; DNA-Binding Proteins ; Tumor Suppressor Proteins ; Metformin (9100L32L2N) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
    Language English
    Publishing date 2012-03-28
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 1108734-1
    ISSN 1546-1718 ; 1061-4036
    ISSN (online) 1546-1718
    ISSN 1061-4036
    DOI 10.1038/ng.2234
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 3613: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 46: Show issues

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

To top