David A Hinds, Lisa M Bain, Arnulf Langhammer, 23andMe Research Team, Stephan Weidinger, BIOS consortium, Oliver Hummel, Patrik K E Magnusson, Gonçalo R Abecasis, Brunilda Balliu, Sarah Grosche, Hansjörg Baurecht, Lavinia Paternoster, Edward Mountjoy, Joana A Revez, Ronald B Melles, Young-Ae Lee, Eric Jorgenson, AAGC collaborators, Melanie C Matheson, Kristian Hveem, Jorge Esparza-Gordillo, Natalija Novak, Shyamali C Dharmage, Annika Tillander, Christian Gieger, Jonas B Nielsen, Ingo Marenholz, Stefan Karrasch, Maiken E Gabrielsen, Jie Zheng, John S Witte, Jouke-Jan Hottenga, Robert Karlsson, Konstantin Strauch, Lars G Fritsche, Norbert Hübner, Dorret I Boomsma, Jonathan Beesley, Cristen J Willer, Melanie Hotze, Mari Løset, Gonneke Willemsen, Yi Lu, Holger Schulz, Gerard H Koppelman, Ben M Brumpton, Catarina Almqvist, Oddgeir L Holmen, Wei Zhou, Elke Rodríguez, Manuel A Ferreira, Philip J Thompson, Kimberley Burrows, Vilhelmina Ullemar, Rick Jansen, Nicholas G Martin, Andre Franke, Georg Homuth, David L Duffy, Judith M Vonk, Chris W Medway, Jenny van Dongen, Joshua D Hoffman, LifeLines Cohort Study, Quinta Helmer, Andreas Arnold, Franz Rüschendorf, Carsten O Schmidt, Chao Tian
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.