Search: (WFRF:(Schieck J.)) srt2:(2020-2021) >
Genome-wide associa...
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Hernandez-Pacheco, N
(author)
Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use
- Article/chapterEnglish2021
Publisher, publication year, extent ...
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2020-12-10
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European Respiratory Society (ERS),2021
Numbers
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LIBRIS-ID:oai:prod.swepub.kib.ki.se:146933879
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http://kipublications.ki.se/Default.aspx?queryparsed=id:146933879URI
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https://doi.org/10.1183/13993003.03388-2020DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Substantial variability in response to asthma treatment with inhaled corticosteroids (ICS) has been described among individuals and populations, suggesting the contribution of genetic factors. Nonetheless, only a few genes have been identified to date. We aimed to identify genetic variants associated with asthma exacerbations despite ICS use in European children and young adults and to validate the findings in non-Europeans. Moreover, we explored whether a gene-set enrichment analysis could suggest potential novel asthma therapies.MethodsA genome-wide association study (GWAS) of asthma exacerbations was tested in 2681 children of European descent treated with ICS from eight studies. Suggestive association signals were followed up for replication in 538 European asthma patients. Further evaluation was performed in 1773 non-Europeans. Variants revealed by published GWAS were assessed for replication. Additionally, gene-set enrichment analysis focused on drugs was performed.Results10 independent variants were associated with asthma exacerbations despite ICS treatment in the discovery phase (p≤5×10−6). Of those, one variant at theCACNA2D3-WNT5Alocus was nominally replicated in Europeans (rs67026078; p=0.010), but this was not validated in non-European populations. Five other genes associated with ICS response in previous studies were replicated. Additionally, an enrichment of associations in genes regulated by trichostatin A treatment was found.ConclusionsThe intergenic region ofCACNA2D3andWNT5Awas revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response.
Added entries (persons, corporate bodies, meetings, titles ...)
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Vijverberg, SJ
(author)
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Herrera-Luis, E
(author)
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Li, J
(author)
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Sio, YY
(author)
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Granell, R
(author)
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Corrales, A
(author)
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Maroteau, C
(author)
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Lethem, R
(author)
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Perez-Garcia, J
(author)
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Farzan, N
(author)
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Repnik, K
(author)
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Gorenjak, M
(author)
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Soares, P
(author)
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Karimi, L
(author)
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Schieck, M
(author)
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Perez-Mendez, L
(author)
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Berce, V
(author)
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Tavendale, R
(author)
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Eng, C
(author)
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Sardon, O
(author)
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Kull, IKarolinska Institutet
(author)
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Mukhopadhyay, S
(author)
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Pirmohamed, M
(author)
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Verhamme, KMC
(author)
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Burchard, EG
(author)
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Kabesch, M
(author)
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Hawcutt, DB
(author)
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Melen, EKarolinska Institutet
(author)
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Potocnik, U
(author)
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Chew, FT
(author)
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Tantisira, KG
(author)
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Turner, S
(author)
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Palmer, CN
(author)
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Flores, C
(author)
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Pino-Yanes, M
(author)
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Maitland-van der Zee, AH
(author)
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Karolinska Institutet
(creator_code:org_t)
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In:The European respiratory journal: European Respiratory Society (ERS)57:51399-30030903-1936
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Hernandez-Pachec ...
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Vijverberg, SJ
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Herrera-Luis, E
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Li, J
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Sio, YY
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Granell, R
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Corrales, A
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Maroteau, C
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Lethem, R
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Perez-Garcia, J
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Farzan, N
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Repnik, K
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Gorenjak, M
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Soares, P
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Karimi, L
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Schieck, M
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Perez-Mendez, L
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Berce, V
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Tavendale, R
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Eng, C
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Sardon, O
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Kull, I
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Mukhopadhyay, S
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Pirmohamed, M
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Verhamme, KMC
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Burchard, EG
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Kabesch, M
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Hawcutt, DB
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Melen, E
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Potocnik, U
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Chew, FT
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Tantisira, KG
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Turner, S
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Palmer, CN
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Flores, C
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Pino-Yanes, M
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Maitland-van der ...
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The European res ...
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Karolinska Institutet