LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 7 of total 7

Search options

  1. Article ; Online: Exploring the overlap between rheumatoid arthritis susceptibility loci and long non-coding RNA annotations.

    James Ding / Chenfu Shi / John Bowes / Stephen Eyre / Gisela Orozco

    PLoS ONE, Vol 15, Iss 3, p e

    2020  Volume 0223939

    Abstract: Whilst susceptibility variants for many complex diseases, such as rheumatoid arthritis (RA), have been well characterised, the mechanism by which risk is mediated is still unclear for many loci. This is especially true for the majority of variants that ... ...

    Abstract Whilst susceptibility variants for many complex diseases, such as rheumatoid arthritis (RA), have been well characterised, the mechanism by which risk is mediated is still unclear for many loci. This is especially true for the majority of variants that do not affect protein-coding regions. lncRNA represent a group of molecules that have been shown to be enriched amongst variants associated with RA and other complex diseases, compared to random variants. In order to establish to what degree direct disruption of lncRNA may represent a potential mechanism for mediating RA susceptibility, we chose to further explore this overlap. By testing the ability of annotated features to improve a model of disease susceptibility, we were able to demonstrate a local enrichment of enhancers from immune-relevant cell types amongst RA susceptibility variants (log2 enrichment 3.40). This was not possible for lncRNA annotations in general, however a small, but significant enrichment was observed for immune-enriched lncRNA (log2 enrichment 0.867002). This enrichment was no longer apparent when the model was conditioned on immune-relevant enhancers (log2 enrichment -0.372734), suggesting that direct disruption of lncRNA sequence, independent of enhancer disruption, does not represent a major mechanism by which susceptibility to complex diseases is mediated. Furthermore, we demonstrated that, in keeping with general lncRNA characteristics, immune-enriched lncRNA are expressed at low levels that may not be amenable to functional characterisation.
    Keywords Medicine ; R ; Science ; Q
    Subject code 572
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  2. Article ; Online: Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis

    Jing Yang / Amanda McGovern / Paul Martin / Kate Duffus / Xiangyu Ge / Peyman Zarrineh / Andrew P. Morris / Antony Adamson / Peter Fraser / Magnus Rattray / Stephen Eyre

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to ... ...

    Abstract Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to identify functional enhancers and demonstrate interactions of expression quantitative trait loci with target genes in rheumatoid arthritis.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  3. Article ; Online: Analysis of chromatin organization and gene expression in T cells identifies functional genes for rheumatoid arthritis

    Jing Yang / Amanda McGovern / Paul Martin / Kate Duffus / Xiangyu Ge / Peyman Zarrineh / Andrew P. Morris / Antony Adamson / Peter Fraser / Magnus Rattray / Stephen Eyre

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to ... ...

    Abstract Although genome-wide association studies have identified genetic variation contributing to disease risk, assigning causal genes is challenging. Here, the authors generate ATAC-seq, Hi-C, Capture Hi-C and RNA-seq data in stimulated CD4+ T cells to identify functional enhancers and demonstrate interactions of expression quantitative trait loci with target genes in rheumatoid arthritis.
    Keywords Science ; Q
    Language English
    Publishing date 2020-09-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  4. Article ; Online: Functional genomics atlas of synovial fibroblasts defining rheumatoid arthritis heritability

    Xiangyu Ge / Mojca Frank-Bertoncelj / Kerstin Klein / Amanda McGovern / Tadeja Kuret / Miranda Houtman / Blaž Burja / Raphael Micheroli / Chenfu Shi / Miriam Marks / Andrew Filer / Christopher D. Buckley / Gisela Orozco / Oliver Distler / Andrew P. Morris / Paul Martin / Stephen Eyre / Caroline Ospelt

    Genome Biology, Vol 22, Iss 1, Pp 1-

    2021  Volume 39

    Abstract: Abstract Background Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded stromal cells, such as ... ...

    Abstract Abstract Background Genome-wide association studies have reported more than 100 risk loci for rheumatoid arthritis (RA). These loci are shown to be enriched in immune cell-specific enhancers, but the analysis so far has excluded stromal cells, such as synovial fibroblasts (FLS), despite their crucial involvement in the pathogenesis of RA. Here we integrate DNA architecture, 3D chromatin interactions, DNA accessibility, and gene expression in FLS, B cells, and T cells with genetic fine mapping of RA loci. Results We identify putative causal variants, enhancers, genes, and cell types for 30–60% of RA loci and demonstrate that FLS account for up to 24% of RA heritability. TNF stimulation of FLS alters the organization of topologically associating domains, chromatin state, and the expression of putative causal genes such as TNFAIP3 and IFNAR1. Several putative causal genes constitute RA-relevant functional networks in FLS with roles in cellular proliferation and activation. Finally, we demonstrate that risk variants can have joint-specific effects on target gene expression in RA FLS, which may contribute to the development of the characteristic pattern of joint involvement in RA. Conclusion Overall, our research provides the first direct evidence for a causal role of FLS in the genetic susceptibility for RA accounting for up to a quarter of RA heritability.
    Keywords Functional genomics ; Stromal cells ; Rheumatoid arthritis ; Fibroblast-like synoviocytes ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  5. Article ; Online: Towards stratified treatment of JIA

    Stephanie J.W. Shoop-Worrall / Saskia Lawson-Tovey / Lucy R. Wedderburn / Kimme L. Hyrich / Nophar Geifman / Aline Kimonyo / Alyssia McNeece / Andrew Dick / Andrew Morris / Annie Yarwood / Athimalaipet Ramanan / Bethany R. Jebson / Chris Wallace / Daniela Dastros-Pitei / Damian Tarasek / Elizabeth Ralph / Emil Carlsson / Emily Robinson / Emma Sumner /
    Fatema Merali / Fatjon Dekaj / Helen Neale / Hussein Al-Mossawi / Jacqui Roberts / Jenna F. Gritzfeld / Joanna Fairlie / John Bowes / John Ioannou / Melissa Kartawinata / Melissa Tordoff / Michael Barnes / Michael W. Beresford / Michael Stadler / Paul Martin / Rami Kallala / Sandra Ng / Samantha Smith / Sarah Clarke / Soumya Raychaudhuri / Stephen Eyre / Sumanta Mukherjee / Teresa Duerr / Thierry Sornasse / Vasiliki Alexiou / Victoria J. Burton / Wei-Yu Lin / Wendy Thomson / Zoe Wanstall

    EBioMedicine, Vol 100, Iss , Pp 104946- (2024)

    machine learning identifies subtypes in response to methotrexate from four UK cohortsResearch in context

    2024  

    Abstract: Summary: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To ... ...

    Abstract Summary: Background: Methotrexate (MTX) is the gold-standard first-line disease-modifying anti-rheumatic drug for juvenile idiopathic arthritis (JIA), despite only being either effective or tolerated in half of children and young people (CYP). To facilitate stratified treatment of early JIA, novel methods in machine learning were used to i) identify clusters with distinct disease patterns following MTX initiation; ii) predict cluster membership; and iii) compare clusters to existing treatment response measures. Methods: Discovery and verification cohorts included CYP who first initiated MTX before January 2018 in one of four UK multicentre prospective cohorts of JIA within the CLUSTER consortium. JADAS components (active joint count, physician (PGA) and parental (PGE) global assessments, ESR) were recorded at MTX start and over the following year.Clusters of MTX ‘response’ were uncovered using multivariate group-based trajectory modelling separately in discovery and verification cohorts. Clusters were compared descriptively to ACR Pedi 30/90 scores, and multivariate logistic regression models predicted cluster-group assignment. Findings: The discovery cohorts included 657 CYP and verification cohorts 1241 CYP. Six clusters were identified: Fast improvers (11%), Slow Improvers (16%), Improve-Relapse (7%), Persistent Disease (44%), Persistent PGA (8%) and Persistent PGE (13%), the latter two characterised by improvement in all features except one. Factors associated with clusters included ethnicity, ILAR category, age, PGE, and ESR scores at MTX start, with predictive model area under the curve values of 0.65–0.71. Singular ACR Pedi 30/90 scores at 6 and 12 months could not capture speeds of improvement, relapsing courses or diverging disease patterns. Interpretation: Six distinct patterns following initiation of MTX have been identified using methods in artificial intelligence. These clusters demonstrate the limitations in traditional yes/no treatment response assessment (e.g., ACRPedi30) and can form the basis ...
    Keywords Juvenile idiopathic arthritis ; Machine learning ; Treatment outcome ; Epidemiology ; Methotrexate ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 310
    Language English
    Publishing date 2024-02-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  6. Article ; Online: Identifying Causal Genes at the Multiple Sclerosis Associated Region 6q23 Using Capture Hi-C.

    Paul Martin / Amanda McGovern / Jonathan Massey / Stefan Schoenfelder / Kate Duffus / Annie Yarwood / Anne Barton / Jane Worthington / Peter Fraser / Stephen Eyre / Gisela Orozco

    PLoS ONE, Vol 11, Iss 11, p e

    2016  Volume 0166923

    Abstract: Background The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in ... ...

    Abstract Background The chromosomal region 6q23 has been found to be associated with multiple sclerosis (MS) predisposition through genome wide association studies (GWAS). There are four independent single nucleotide polymorphisms (SNPs) associated with MS in this region, which spans around 2.5 Mb. Most GWAS variants associated with complex traits, including these four MS associated SNPs, are non-coding and their function is currently unknown. However, GWAS variants have been found to be enriched in enhancers and there is evidence that they may be involved in transcriptional regulation of their distant target genes through long range chromatin looping. Aim The aim of this work is to identify causal disease genes in the 6q23 locus by studying long range chromatin interactions, using the recently developed Capture Hi-C method in human T and B-cell lines. Interactions involving four independent associations unique to MS, tagged by rs11154801, rs17066096, rs7769192 and rs67297943 were analysed using Capture Hi-C Analysis of Genomic Organisation (CHiCAGO). Results We found that the pattern of chromatin looping interactions in the MS 6q23 associated region is complex. Interactions cluster in two regions, the first involving the rs11154801 region and a second containing the rs17066096, rs7769192 and rs67297943 SNPs. Firstly, SNPs located within the AHI1 gene, tagged by rs11154801, are correlated with expression of AHI1 and interact with its promoter. These SNPs also interact with other potential candidate genes such as SGK1 and BCLAF1. Secondly, the rs17066096, rs7769192 and rs67297943 SNPs interact with each other and with immune-related genes such as IL20RA, IL22RA2, IFNGR1 and TNFAIP3. Finally, the above-mentioned regions interact with each other and therefore, may co-regulate these target genes. Conclusion These results suggest that the four 6q23 variants, independently associated with MS, are involved in the regulation of several genes, including immune genes. These findings could help understand mechanisms of disease and ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

  7. Article ; Online: Identification of the tyrosine-protein phosphatase non-receptor type 2 as a rheumatoid arthritis susceptibility locus in europeans.

    Joanna E Cobb / Darren Plant / Edward Flynn / Meriem Tadjeddine / Philippe Dieudé / François Cornélis / Lisbeth Ärlestig / Solbritt Rantapää Dahlqvist / George Goulielmos / Dimitrios T Boumpas / Prodromos Sidiropoulos / Sophine B Krintel / Lykke M Ørnbjerg / Merete L Hetland / Lars Klareskog / Thomas Haeupl / Andrew Filer / Christopher D Buckley / Karim Raza /
    Torsten Witte / Reinhold E Schmidt / Oliver FitzGerald / Douglas Veale / Stephen Eyre / Jane Worthington

    PLoS ONE, Vol 8, Iss 6, p e

    2013  Volume 66456

    Abstract: Objectives Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance ...

    Abstract Objectives Genome-wide association studies have facilitated the identification of over 30 susceptibility loci for rheumatoid arthritis (RA). However, evidence for a number of potential susceptibility genes have not so far reached genome-wide significance in studies of Caucasian RA. Methods A cohort of 4286 RA patients from across Europe and 5642 population matched controls were genotyped for 25 SNPs, then combined in a meta-analysis with previously published data. Results Significant evidence of association was detected for nine SNPs within the European samples. When meta-analysed with previously published data, 21 SNPs were associated with RA susceptibility. Although SNPs in the PTPN2 gene were previously reported to be associated with RA in both Japanese and European populations, we show genome-wide evidence for a different SNP within this gene associated with RA susceptibility in an independent European population (rs7234029, P = 4.4×10(-9)). Conclusions This study provides further genome-wide evidence for the association of the PTPN2 locus (encoding the T cell protein tyrosine phosphastase) with Caucasian RA susceptibility. This finding adds to the growing evidence for PTPN2 being a pan-autoimmune susceptibility gene.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top