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Sökning: onr:"swepub:oai:DiVA.org:liu-188930" > Eleven loci with ne...

Eleven loci with new reproducible genetic associations with allergic disease risk.

Ferreira, Manuel A R (författare)
Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Australia
Vonk, Judith M (författare)
Epidemiology, University of Groningen, University Medical Center Groningen, Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands
Baurecht, Hansjörg (författare)
Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
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Marenholz, Ingo (författare)
Max 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
Tian, Chao (författare)
23andMe, Inc, Mountain View, Calif
Hoffman, Joshua D (författare)
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, Calif
Helmer, Quinta (författare)
Department Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, The Netherlands
Tillander, Annika (författare)
Linköpings universitet,Statistik och maskininlärning,Filosofiska fakulteten,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
Ullemar, Vilhelmina (författare)
Karolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
Lu, Yi (författare)
Karolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
Rüschendorf, Franz (författare)
Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany
Hinds, David A (författare)
23andMe, Inc, Mountain View, Calif
Hübner, Norbert (författare)
Max Delbrück Center (MDC) for Molecular Medicine, Berlin, Germany
Weidinger, Stephan (författare)
Department of Dermatology, Allergology and Venereology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany
Magnusson, Patrik K E (författare)
Karolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
Jorgenson, Eric (författare)
Division of Research, Kaiser Permanente Northern California, Oakland, Calif
Lee, Young-Ae (författare)
Max 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
Boomsma, Dorret I (författare)
Department Biological Psychology, Netherlands Twin Register, Vrije University, Amsterdam, The Netherlands
Karlsson, Robert (författare)
Karolinska Institutet,Department of Medical Epidemiology and Biostatistics and the Swedish Twin Registry, Karolinska Institutet, Stockholm, Sweden
Almqvist, Catarina (författare)
Karolinska 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
Koppelman, Gerard H (författare)
University 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
Paternoster, Lavinia (författare)
MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom
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 (creator_code:org_t)
Elsevier BV, 2019
2019
Engelska.
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 143:2, s. 691-699
Relaterad länk:
http://www.jacionlin...
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https://urn.kb.se/re...
https://doi.org/10.1...
http://kipublication...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

Rhinitis
atopic dermatitis
atopy
genome-wide association study
transcriptome

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