Title |
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
|
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Published in |
Nature Genetics, October 2017
|
DOI | 10.1038/ng.3985 |
Pubmed ID | |
Authors |
Manuel A Ferreira, Judith M Vonk, Hansjörg Baurecht, Ingo Marenholz, Chao Tian, Joshua D Hoffman, Quinta Helmer, Annika Tillander, Vilhelmina Ullemar, Jenny van Dongen, Yi Lu, Franz Rüschendorf, Jorge Esparza-Gordillo, Chris W Medway, Edward Mountjoy, Kimberley Burrows, Oliver Hummel, Sarah Grosche, Ben M Brumpton, John S Witte, Jouke-Jan Hottenga, Gonneke Willemsen, Jie Zheng, Elke Rodríguez, Melanie Hotze, Andre Franke, Joana A Revez, Jonathan Beesley, Melanie C Matheson, Shyamali C Dharmage, Lisa M 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 O 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 |
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 × 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 29 | 24% |
United States | 24 | 20% |
Canada | 5 | 4% |
Netherlands | 3 | 2% |
Norway | 3 | 2% |
Australia | 2 | 2% |
France | 2 | 2% |
New Zealand | 1 | <1% |
Qatar | 1 | <1% |
Other | 9 | 7% |
Unknown | 44 | 36% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 76 | 62% |
Scientists | 36 | 29% |
Practitioners (doctors, other healthcare professionals) | 7 | 6% |
Science communicators (journalists, bloggers, editors) | 4 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 398 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 100 | 25% |
Student > Ph. D. Student | 66 | 17% |
Student > Master | 38 | 10% |
Student > Bachelor | 30 | 8% |
Other | 18 | 5% |
Other | 59 | 15% |
Unknown | 87 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 85 | 21% |
Medicine and Dentistry | 68 | 17% |
Agricultural and Biological Sciences | 57 | 14% |
Immunology and Microbiology | 21 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 14 | 4% |
Other | 53 | 13% |
Unknown | 100 | 25% |