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  1. Article ; Online: Decoding the genetic and epigenetic basis of asthma.

    Stikker, Bernard S / Hendriks, Rudi W / Stadhouders, Ralph

    Allergy

    2023  Volume 78, Issue 4, Page(s) 940–956

    Abstract: Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms ... ...

    Abstract Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms underlying disease susceptibility, asthma is frequently studied in genome-wide association studies (GWAS), which have identified thousands of genetic variants associated with asthma development. Virtually all these genetic variants reside in non-coding genomic regions, which has obscured the functional impact of asthma-associated variants and their translation into disease-relevant mechanisms. Recent advances in genomics technology and epigenetics now offer methods to link genetic variants to gene regulatory elements embedded within non-coding regions, which have started to unravel the molecular mechanisms underlying the complex (epi)genetics of asthma. Here, we provide an integrated overview of (epi)genetic variants associated with asthma, focusing on efforts to link these disease associations to biological insight into asthma pathophysiology using state-of-the-art genomics methodology. Finally, we provide a perspective as to how decoding the genetic and epigenetic basis of asthma has the potential to transform clinical management of asthma and to predict the risk of asthma development.
    MeSH term(s) Humans ; Genome-Wide Association Study ; Epigenesis, Genetic ; Epigenomics ; Asthma/genetics ; Genomics ; Genetic Predisposition to Disease
    Language English
    Publishing date 2023-02-15
    Publishing country Denmark
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Decoding the genetic and epigenetic basis of asthma

    Stikker, Bernard S. / Hendriks, Rudi W. / Stadhouders, Ralph

    Allergy 2023 Apr., v. 78, no. 4, p. 940-956

    2023  , Page(s) 940–956

    Abstract: Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms ... ...

    Abstract Asthma is a complex and heterogeneous chronic inflammatory disease of the airways. Alongside environmental factors, asthma susceptibility is strongly influenced by genetics. Given its high prevalence and our incomplete understanding of the mechanisms underlying disease susceptibility, asthma is frequently studied in genome‐wide association studies (GWAS), which have identified thousands of genetic variants associated with asthma development. Virtually all these genetic variants reside in non‐coding genomic regions, which has obscured the functional impact of asthma‐associated variants and their translation into disease‐relevant mechanisms. Recent advances in genomics technology and epigenetics now offer methods to link genetic variants to gene regulatory elements embedded within non‐coding regions, which have started to unravel the molecular mechanisms underlying the complex (epi)genetics of asthma. Here, we provide an integrated overview of (epi)genetic variants associated with asthma, focusing on efforts to link these disease associations to biological insight into asthma pathophysiology using state‐of‐the‐art genomics methodology. Finally, we provide a perspective as to how decoding the genetic and epigenetic basis of asthma has the potential to transform clinical management of asthma and to predict the risk of asthma development.
    Keywords asthma ; disease susceptibility ; epigenetics ; genes ; genomics ; pathophysiology ; risk
    Language English
    Dates of publication 2023-04
    Size p. 940-956.
    Publishing place John Wiley & Sons, Inc
    Document type Article ; Online
    ZDB-ID 391933-x
    ISSN 1398-9995 ; 0105-4538
    ISSN (online) 1398-9995
    ISSN 0105-4538
    DOI 10.1111/all.15666
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Cologne/Königswinter

    Uh III Zs.150: 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 125: Show issues

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  3. Article: Severe COVID-19 associated variants linked to chemokine receptor gene control in monocytes and macrophages.

    Stikker, Bernard / Stik, Grégoire / Hendriks, Rudi W / Stadhouders, Ralph

    bioRxiv : the preprint server for biology

    2021  

    Abstract: Genome-wide association studies have identified 3p21.31 as the main risk locus for severe disease in COVID-19 patients, although underlying biological mechanisms remain elusive. We performed a comprehensive epigenomic dissection of the 3p21.31 locus, ... ...

    Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe disease in COVID-19 patients, although underlying biological mechanisms remain elusive. We performed a comprehensive epigenomic dissection of the 3p21.31 locus, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several tissue-homing chemokine receptor (CCR) genes in monocytes and macrophages. Risk SNPs colocalized with regulatory elements and were linked to increased expression of
    Language English
    Publishing date 2021-06-11
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2021.01.22.427813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages

    Stikker, Bernard S. / Stik, Grégoire / van Ouwerkerk, Antoinette F. / Trap, Lianne / Spicuglia, Salvatore / Hendriks, Rudi W. / Stadhouders, Ralph

    Genome biology. 2022 Dec., v. 23, no. 1

    2022  

    Abstract: Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory ... ...

    Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1, CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.
    Keywords CCR1 receptor ; COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; chromatin ; dissection ; epigenome ; genes ; loci ; macrophages ; monocytes ; risk
    Language English
    Dates of publication 2022-12
    Size p. 96.
    Publishing place BioMed Central
    Document type Article
    ZDB-ID 2040529-7
    ISSN 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-022-02669-z
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages.

    Stikker, Bernard S / Stik, Grégoire / van Ouwerkerk, Antoinette F / Trap, Lianne / Spicuglia, Salvatore / Hendriks, Rudi W / Stadhouders, Ralph

    Genome biology

    2022  Volume 23, Issue 1, Page(s) 96

    Abstract: Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory ... ...

    Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1, CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.
    MeSH term(s) COVID-19/genetics ; Genome-Wide Association Study ; Humans ; Macrophages/metabolism ; Monocytes/metabolism ; Receptors, CCR5/genetics ; Receptors, CCR5/metabolism ; Receptors, Chemokine/genetics ; Receptors, Chemokine/metabolism ; SARS-CoV-2
    Chemical Substances Receptors, CCR5 ; Receptors, Chemokine
    Language English
    Publishing date 2022-04-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2040529-7
    ISSN 1474-760X ; 1474-760X
    ISSN (online) 1474-760X
    ISSN 1474-760X
    DOI 10.1186/s13059-022-02669-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: 3D chromatin reprogramming primes human memory T

    Onrust-van Schoonhoven, Anne / de Bruijn, Marjolein J W / Stikker, Bernard / Brouwer, Rutger W W / Braunstahl, Gert-Jan / van IJcken, Wilfred F J / Graf, Thomas / Huylebroeck, Danny / Hendriks, Rudi W / Stik, Grégoire / Stadhouders, Ralph

    Science immunology

    2023  Volume 8, Issue 85, Page(s) eadg3917

    Abstract: Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate, but how they efficiently "recall" an inflammatory transcriptional program remains unclear. Here, we show that human ... ...

    Abstract Memory T cells provide long-lasting defense responses through their ability to rapidly reactivate, but how they efficiently "recall" an inflammatory transcriptional program remains unclear. Here, we show that human CD4
    MeSH term(s) Humans ; Chromatin/genetics ; Gene Expression Regulation ; Transcription Factors/genetics ; Promoter Regions, Genetic
    Chemical Substances Chromatin ; Transcription Factors
    Language English
    Publishing date 2023-07-07
    Publishing country United States
    Document type Journal Article
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.adg3917
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19

    Stadhouders, Ralph / Hendriks, Rudi W. / Stikker, Bernard / Stik, Gregoire

    bioRxiv

    Abstract: Genome-wide association studies have identified 3p21.31 as the main risk locus for severe symptoms and hospitalization in COVID-19 patients. To elucidate the mechanistic basis of this genetic association, we performed a comprehensive epigenomic ... ...

    Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe symptoms and hospitalization in COVID-19 patients. To elucidate the mechanistic basis of this genetic association, we performed a comprehensive epigenomic dissection of the 3p21.31 locus. Our analyses pinpoint activating variants in regulatory regions of the chemokine receptor-encoding CCR1 gene as potentially pathogenic by enhancing infiltration of monocytes and macrophages into the lungs of patients with severe COVID-19.
    Keywords covid19
    Language English
    Publishing date 2021-01-22
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2021.01.22.427813
    Database COVID19

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  8. Article ; Online: Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages

    Bernard S. Stikker / Grégoire Stik / Antoinette F. van Ouwerkerk / Lianne Trap / Salvatore Spicuglia / Rudi W. Hendriks / Ralph Stadhouders

    Genome Biology, Vol 23, Iss 1, Pp 1-

    2022  Volume 10

    Abstract: Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D ... ...

    Abstract Abstract Genome-wide association studies have identified 3p21.31 as the main risk locus for severe COVID-19, although underlying mechanisms remain elusive. We perform an epigenomic dissection of 3p21.31, identifying a CTCF-dependent tissue-specific 3D regulatory chromatin hub that controls the activity of several chemokine receptor genes. Risk SNPs colocalize with regulatory elements and are linked to increased expression of CCR1, CCR2 and CCR5 in monocytes and macrophages. As excessive organ infiltration of inflammatory monocytes and macrophages is a hallmark of severe COVID-19, our findings provide a rationale for the genetic association of 3p21.31 variants with elevated risk of hospitalization upon SARS-CoV-2 infection.
    Keywords SARS-CoV-2 ; COVID-19 ; 3p21.31 ; GWAS ; Monocyte ; Macrophage ; Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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