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Title: Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
Author(s): M.A.R. Ferreira, J.M. Vonk, H. Baurecht, I. Marenholz, C. Tian, J.D. Hoffman, Q. Helmer, A. Tillander, V. Ullemar, J. van Dongen, J.J. Hottenga, G. Willemsen, 23andMe Research Team, AAGC Collaborators, BIOS Consortium, LifeLines Cohort Study, S. Weidinger, P.K.E. Magnusson, R. Jansen, E. Jorgenson, Y.A. Lee, D.I. Boomsma, C. Almqvist, R. Karlsson, G.H. Koppelman, L. Paternoster and many others
Journal: Nature Genetics
Year: 2017
Month: December
Day: 1
Volume: 49
Issue: 12
Pages: 1752-1757
DOI: 10.1038/ng.3985
File URL: https://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3985.html
Web URL: http://www.tweelingenregister.org/publicaties/wetenschappelijke-publicaties/supplementary-materials/
Keywords: Allergy; Asthma; Atopic dermatitis; Genome-wide association studies
Abstract: Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals1, partly because of a shared genetic origin2, 3, 4. 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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