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Eleven loci with ne...
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Ferreira, Manuel A RGenetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
(author)
Eleven loci with new reproducible genetic associations with allergic disease risk.
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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Elsevier BV,2019
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-188930
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-188930URI
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https://doi.org/10.1016/j.jaci.2018.03.012DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:140220465URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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BACKGROUND: A recent genome-wide association study (GWAS) identified 99 loci that contain genetic risk variants shared between asthma, hay fever, and eczema. Many more risk loci shared between these common allergic diseases remain to be discovered, which could point to new therapeutic opportunities.OBJECTIVE: We sought to identify novel risk loci shared between asthma, hay fever, and eczema by applying a gene-based test of association to results from a published GWAS that included data from 360,838 subjects.METHODS: We used approximate conditional analysis to adjust the results from the published GWAS for the effects of the top risk variants identified in that study. We then analyzed the adjusted GWAS results with the EUGENE gene-based approach, which combines evidence for association with disease risk across regulatory variants identified in different tissues. Novel gene-based associations were followed up in an independent sample of 233,898 subjects from the UK Biobank study.RESULTS: Of the 19,432 genes tested, 30 had a significant gene-based association at a Bonferroni-corrected P value of 2.5 × 10-6. Of these, 20 were also significantly associated (P < .05/30 = .0016) with disease risk in the replication sample, including 19 that were located in 11 loci not reported to contain allergy risk variants in previous GWASs. Among these were 9 genes with a known function that is directly relevant to allergic disease: FOSL2, VPRBP, IPCEF1, PRR5L, NCF4, APOBR, IL27, ATXN2L, and LAT. For 4 genes (eg, ATXN2L), a genetically determined decrease in gene expression was associated with decreased allergy risk, and therefore drugs that inhibit gene expression or function are predicted to ameliorate disease symptoms. The opposite directional effect was observed for 14 genes, including IL27, a cytokine known to suppress TH2 responses.CONCLUSION: Using a gene-based approach, we identified 11 risk loci for allergic disease that were not reported in previous GWASs. Functional studies that investigate the contribution of the 19 associated genes to the pathophysiology of allergic disease and assess their therapeutic potential are warranted.
Subject headings and genre
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Vonk, Judith MEpidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
(author)
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Baurecht, HansjörgDepartment of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
(author)
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Marenholz, IngoMax Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany. Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany
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Tian, Chao23andMe, Inc, Mountain View, Calif
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Hoffman, Joshua DDepartment of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, Calif
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Helmer, QuintaDepartment Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, The Netherlands
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Tillander, AnnikaDepartment of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden(Swepub:liu)annti27
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Ullemar, VilhelminaKarolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
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Lu, YiKarolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
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Rüschendorf, FranzMax Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany
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Hinds, David A23andMe, Inc, Mountain View, Calif
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Hübner, NorbertMax Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany
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Weidinger, StephanDepartment of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
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Magnusson, Patrik K EKarolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
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Jorgenson, EricDivision of Research, Kaiser Permanente Northern California, Oakland, Calif
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Lee, Young-AeMax Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany. Clinic for Pediatric Allergy, Experimental and Clinical Research Center of Charité Universitätsmedizin Berlin and Max Delbrück Center, Berlin, Germany
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Boomsma, Dorret IDepartment Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, The Netherlands
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Karlsson, RobertKarolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
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Almqvist, CatarinaKarolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden. Pediatric Allergy and Pulmonology Unit at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
(author)
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Koppelman, Gerard HUniversity of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Pediatric Pulmonology and Pediatric Allergology, and University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
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Paternoster, LaviniaMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, AustraliaEpidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
(creator_code:org_t)
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In:Journal of Allergy and Clinical Immunology: Elsevier BV143:2, s. 691-6990091-67491097-6825
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Ferreira, Manuel ...
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Vonk, Judith M
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Baurecht, Hansjö ...
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Marenholz, Ingo
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Tian, Chao
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Helmer, Quinta
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Tillander, Annik ...
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Ullemar, Vilhelm ...
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Lu, Yi
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Rüschendorf, Fra ...
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Hinds, David A
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Hübner, Norbert
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Weidinger, Steph ...
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Magnusson, Patri ...
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Jorgenson, Eric
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Lee, Young-Ae
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Boomsma, Dorret ...
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Karlsson, Robert
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Almqvist, Catari ...
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