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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)
Open Access Green as soon as Postprint is submitted to ZB.
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
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