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Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
Open accessAbstract
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.
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“The main epigenetic studies in AD are related to the DNA methylation of two genes, NLRP2 (involved in macrophage activity) and PITPNM2 (related to neutrophils), both associated with smoking.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [41]
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“Also, the association of eczema herpeticum and serum IgE levels with methylation in the IL-4 and IL-13 genes.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [41]
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“Although little is known about FAM105A function, GWAS of allergic diseases implicates a credible missense risk variant in this gene (Ferreira et al., 2017).”
From Genome-wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function (2018) · cites this paper as Ferreira et al., 2017
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Metadata
- Authors
- 23andMe Research Team, Ferreira, M. A., collaborators, A., BIOS consortium, Study, L. C., Vonk, J. M., Baurecht, H., Marenholz, I., Tian, C., Hoffman, J. D., Helmer, Q., Tillander, A., Ullemar, V., van Dongen, J., Lu, Y., Rüschendorf, F., Esparza-Gordillo, J., Medway, C. W., Mountjoy, E., Burrows, K., Hummel, O., Grosche, S., Brumpton, B. M., Witte, J. S., Hottenga, J.-J., Willemsen, G., Zheng, J., Rodríguez, E., Hotze, M., Franke, A., Revez, J. A., Beesley, J., Matheson, M. C., Dharmage, S. C., Bain, L. M., Fritsche, L. G., Gabrielsen, M. E., Balliu, B., Nielsen, J. B., Zhou, W., Hveem, K., Langhammer, A., Holmen, O. L., Løset, M., Abecasis, G. R., Willer, C. J., Arnold, A., Homuth, G., Schmidt, C. O., Thompson, P. J., Martin, N. G., Duffy, D. L., Novak, N., Schulz, H., Karrasch, S., Gieger, C., Strauch, K., Melles, R. B., Hinds, D. A., Hübner, N., Weidinger, S., Magnusson, P. K. E., Jansen, R., Jorgenson, E., Lee, Y.-A., Boomsma, D. I., Almqvist, C., Karlsson, R., Koppelman, G. H., & Paternoster, L.
- Affiliations
- QIMR Berghofer Medical Research Institute (AU)
- University Medical Center Groningen (NL)
- University Hospital Schleswig-Holstein (DE)
- 23andMe (United States) (US)
- University of California, San Francisco (US)
- Karolinska Institutet (SE)
- Max Delbrück Center (DE)
- University of Bristol (GB)
- Norwegian University of Science and Technology (NO)
- Christian-Albrechts-Universität zu Kiel (DE)
- The University of Melbourne (AU)
- University of Michigan (US)
- Universitätsmedizin Greifswald (DE)
- The University of Western Australia (AU)
- University Hospital Bonn (DE)
- Helmholtz Munich (DE)
- Kaiser Permanente (US)
- Karolinska University Hospital (SE)
- Corresponding author
- Ferreira, Manuel A
- ORCID
- Ferreira, Manuel A
- Vonk, Judith M
- Baurecht, Hansjörg
- Marenholz, Ingo
- Tian, Chao
- Hoffman, Joshua D
- Tillander, Annika
- Ullemar, Vilhelmina
- Lu, Yi
- Rüschendorf, Franz
- Mountjoy, Edward
- Burrows, Kimberley
- Hummel, Oliver
- Grosche, Sarah
- Brumpton, Ben M
- Witte, John S
- Hottenga, Jouke-Jan
- Willemsen, Gonneke
- Zheng, Jie
- Rodríguez, Elke
- Franke, Andre
- Revez, Joana A
- Matheson, Melanie C
- Dharmage, Shyamali C
- Fritsche, Lars G
- Gabrielsen, Maiken E
- Balliu, Brunilda
- Nielsen, Jonas B
- Zhou, Wei
- Hveem, Kristian
- Langhammer, Arnulf
- 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
- Venue
- Nature Genetics
- Published
- 2017-10-30
- Volume
- 49
- Issue
- 12
- Pages
- 1752-1757
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC5989923
- OpenAlex
- W2765256236
- Semantic Scholar
- 08c8383033e73b5aa7bee3306e4e91cbd16ae672
- Cited by
- 550
- References
- 51
- Citations by year
- 2026: 44 · 2025: 45 · 2024: 61 · 2023: 62 · 2022: 77 · 2021: 74 · 2020: 78 · 2019: 70 · 2018: 35 · 2017: 3
- FWCI
- 37.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, other-oa)
- Explore Bristol Research (publishedVersion, other-oa)
- VU Research Portal (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion, other-oa)
- UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- Site cant be reached (submittedVersion, other-oa)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Norges Teknisk-Naturvitenskapelige Universitet
- Wellcome Trust (102215)
- QIMR Berghofer Medical Research Institute
- University of Bristol
- Rijksuniversiteit Groningen
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (480-15-001)
- Lundbeckfonden (R220-2016-1434)
- Karolinska Institutet
- Universitair Medisch Centrum Groningen
- St. Olavs Hospital Universitetssykehuset i Trondheim
- Medical Research Council (MR/J012165/1, MC_PC_12028)
- National Cancer Institute (R25CA112355)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Keywords
- asthma, allergic rhinitis, atopic dermatitis, allergic diseases, genetic susceptibility loci, immune gene expression, lymphocyte-mediated immunity, drug repurposing, CpG methylation, transcriptional regulation
- MeSH terms
- Asthma, Eczema, Rhinitis, Allergic, Seasonal, Humans, Hypersensitivity, Phenotype, Risk Factors, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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