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

• Published in: Nature genetics Vol. 49; no. 12; pp. 1752 - 1757
• Main Authors: Ferreira, Manuel A, Vonk, Judith M, Baurecht, Hansjörg, Marenholz, Ingo, Tian, Chao, Hoffman, Joshua D, Helmer, Quinta, Tillander, Annika, Ullemar, Vilhelmina, van Dongen, Jenny, Lu, Yi, Rüschendorf, Franz, Esparza-Gordillo, Jorge, Medway, Chris W, Mountjoy, Edward, Burrows, Kimberley, Hummel, Oliver, Grosche, Sarah, Brumpton, Ben M, Witte, John S, Hottenga, Jouke-Jan, Willemsen, Gonneke, Zheng, Jie, Rodríguez, Elke, Hotze, Melanie, Franke, Andre, Revez, Joana A, Beesley, Jonathan, Matheson, Melanie C, Dharmage, Shyamali C, Bain, Lisa M, Fritsche, Lars G, Gabrielsen, Maiken E, Balliu, Brunilda, Nielsen, Jonas B, Zhou, Wei, Hveem, Kristian, Langhammer, Arnulf, Holmen, Oddgeir L, Løset, Mari, Abecasis, Gonçalo R, Willer, Cristen J, Arnold, Andreas, Homuth, Georg, Schmidt, Carsten O, Thompson, Philip J, Martin, Nicholas G, Duffy, David L, Novak, Natalija, Schulz, Holger, Karrasch, Stefan, Gieger, Christian, Strauch, Konstantin, Melles, Ronald B, Hinds, David A, Hübner, Norbert, Weidinger, Stephan, Magnusson, Patrik K E, Jansen, Rick, Jorgenson, Eric, Lee, Young-Ae, Boomsma, Dorret I, Almqvist, Catarina, Karlsson, Robert, Koppelman, Gerard H, Paternoster, Lavinia
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2017; Nature Publishing Group
• Subjects: 38/39; 45/43; 631/208/205/2138; 692/699/249/2510/1415; 692/699/249/2510/31; 692/699/249/2510/9; Age; Agriculture; Allergic rhinitis; Allergies; Animal Genetics and Genomics; Asthma; Asthma - genetics; Atopic dermatitis; Biological activity; Biomedicine; Cancer Research; CpG islands; Dermatitis; Disease; DNA methylation; Eczema; Eczema - genetics; Gene expression; Gene Function; Genes; Genetic aspects; Genetic effects; Genetic Predisposition to Disease - genetics; Genetic variation; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Hay; Hay fever; Health aspects; Heritability; Human Genetics; Humans; Hypersensitivity - genetics; Immunity; letter; Lymphocytes; Medicin och hälsovetenskap; Methods; Phenotype; Polymorphism, Single Nucleotide; Rhinitis; Rhinitis, Allergic, Seasonal - genetics; Risk analysis; Risk Factors; Risk sharing; Skin diseases; Studies; Transcription
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.3985

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 individuals 1 , partly because of a shared genetic origin 2 , 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.