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

2017; Nature Portfolio; Volume: 49; Issue: 12 Linguagem: Inglês

10.1038/ng.3985

1546-1718

Manuel A. R. Ferreira, Judith M. Vonk, Hansjörg Baurecht, Ingo Marenholz, Chao Tian, Joshua Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Jenny van Dongen, Yi Lu, Franz Rüschendorf, Jorge Esparza-Gordillo, Chris Medway, Edward Mountjoy, Kimberley Burrows, Oliver Hummel, Sarah Grosche, Ben Brumpton, John S. Witte, Jouke‐Jan Hottenga, Gonneke Willemsen, Jie Zheng, Elke Rodríguez, Melanie Hotze, André Franke, Joana Revez, Jonathan Beesley, Melanie C. Matheson, Shyamali C. Dharmage, Lisa Bain, Lars G. Fritsche, Maiken E. Gabrielsen, Brunilda Balliu, Jonas B. Nielsen, Wei Zhou, Kristian Hveem, Arnulf Langhammer, Oddgeir L. Holmen, Mari Løset, Gonçalo R. Abecasis, Cristen J. Willer, Andreas Arnold, Georg Homuth, Carsten Oliver Schmidt, Philip J. Thompson, Nicholas G. Martin, David L. Duffy, Natalija Novak, Holger Schulz, Stefan Karrasch, Christian Gieger, Konstantin Strauch, Ronald B. Melles, David A. Hinds, Norbert Hübner, Stephan Weidinger, Patrik K. E. Magnusson, Rick Jansen, Eric Jorgenson, Young‐Ae Lee, Dorret I. Boomsma, Catarina Almqvist, Robert Karlsson, Gerard H. Koppelman, Lavinia Paternoster,

IL-33, ST2, and ILC Pathways

This large-scale genome-wide association analysis of subjects with asthma, hay fever or eczema provides insights into the shared genetic basis of these allergic diseases. The findings suggest that these diseases partly co-occur because they share many genetic risk variants that dysregulate the expression of immune-related genes. 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.