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

Item Type:Letter
Title:Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
Creators Name: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, Yi, Rueschendorf, 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., Rodriguez, 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. and Paternoster, L.
Abstract: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 x 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.
Keywords:Asthma, Eczema, Genetic Predisposition To Disease, Genome-Wide Association Study, Hypersensitivity, Phenotype, Polymorphism, Single Nucleotide, Rhinitis, Allergic, Seasonal, Risk Factors
Source:Nature Genetics
Publisher:Nature Publishing Group
Page Range:1752-1757
Date:December 2017
Official Publication:https://doi.org/10.1038/ng.3985
External Fulltext:View full text on PubMed Central Europe
PubMed:View item in PubMed

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