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Ferreira, M.A.* ; Vonk, J.M.* ; Baurecht, H.* ; Marenholz, I.* ; Tian, C.* ; Hoffman, J.D.* ; Helmer, Q.* ; Tillander, A.* ; Ullemar, V.* ; van Dongen, J.* ; Lu, Y.* ; Rüschendorf, F.* ; Esparza-Gordillo, J.* ; Medway, C.W.* ; Mountjoy, E.* ; Burrows, K.* ; Hummel, O.* ; Grosche, S.* ; Brumpton, B.M.* ; Witte, J.S.* ; Hottenga, J.J.* ; Willemsen, G.* ; Zheng, J.* ; Rodríguez, E.* ; Hotze, M.* ; Franke, A.* ; Revez, J.A.* ; Beesley, J.* ; Matheson, M.C.* ; Dharmage, S.C.* ; Bain, L.M.* ; Fritsche, L.G.* ; Gabrielsen, M.E.* ; Balliu, B.* ; Nielsen, J.B.* ; Zhou, W.* ; Hveem, K.* ; Langhammer, A.* ; Holmen, O.L.* ; Løset, M.* ; Abecasis, G.R.* ; Willer, C.J.* ; Arnold, A.* ; Homuth, G.* ; Schmidt, C.O.* ; Thompson, P.J.* ; Martin, N.G.* ; Duffy, D.L.* ; Novak, N.* ; Schulz, H. ; Karrasch, S. ; Gieger, C. ; Strauch, K. ; Melles, R.B.* ; Hinds, D.A.* ; Hübner, N.* ; Weidinger, S.* ; Magnusson, P.K.E.* ; Jansen, R.* ; Jorgenson, E.* ; Lee, Y.A.* ; Boomsma, D.I.* ; Almqvist, C.* ; Karlsson, R.* ; Koppelman, G.H.* ; Paternoster, L.*

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.

Nat. Genet. 49, 1752-1757 (2017)
Postprint Research data DOI PMC
Open Access Green
Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10(-8)), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Genome-wide Association; Ld Score Regression; Atopic-dermatitis; Human-cells; Variants; Identification; Rhinitis; Cohort; Twin; Transcriptome
Language english
Publication Year 2017
HGF-reported in Year 2017
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 49, Issue: 12, Pages: 1752-1757 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Genetic Epidemiology (IGE)
POF-Topic(s) 30202 - Environmental Health
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
80000 - German Center for Lung Research
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504000-009
G-504091-004
G-504100-001
G-501800-391
G-503900-003
DOI 10.1038/ng.3985
WOS ID WOS:000416480600015
Scopus ID 85035776645
PubMed ID 29083406
Erfassungsdatum 2017-11-16
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