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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 Forschungsdaten 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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genome-wide Association; Ld Score Regression; Atopic-dermatitis; Human-cells; Variants; Identification; Rhinitis; Cohort; Twin; Transcriptome
Sprache englisch
Veröffentlichungsjahr 2017
HGF-Berichtsjahr 2017
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Zeitschrift Nature Genetics
Quellenangaben Band: 49, Heft: 12, Seiten: 1752-1757 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) 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
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) 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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