Genome-wide integration of genetic and genomic studies of atopic dermatitis: insights into genetic architecture and pathogenesis
Open accessAbstract
Atopic dermatitis (AD) is a common heterogeneous, chronic, itching, and inflammatory skin disease. Genetic studies have identified multiple AD susceptibility genes. However, the genetic architecture of AD has not been elucidated. In this study, we conducted a large-scale meta-analysis of AD (35,647 cases and 1,013,885 controls) to characterize the genetic basis of AD. The heritability of AD in different datasets varied from 0.6 to 7.1%. We identified 31 previously unreported genes by integrating multiomics data. Among the 31 genes, MCL1 was identified as a potential treatment target for AD by mediating gene‒drug interactions. Tissue enrichment analyses and phenome-wide association study provided strong support for the role of the hemic and immune systems in AD. Across 1,207 complex traits and diseases, genetic correlations indicated that AD shared links with multiple respiratory phenotypes. The phenome-wide Mendelian randomization analysis (Mendelian randomization‒phenome-wide association study) revealed that the age of onset of diabetes exhibited a positive causal effect on AD (inverse-variance weighted β = 0.39, SEM = 0.09, P = 2.77 × 10 -5 ). Overall, these results provide important insights into the genetic architecture of AD and will lead to a more thorough and complete understanding of the molecular mechanisms underlying AD.
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There are dozens of AD susceptibility loci characterized in diverse populations, which mediate functions such as response to interferon gamma (IFNγ), innate immunity, T lymphocyte functions, and epidermal barrier dysfunctions.
“There are dozens of AD susceptibility loci characterized in diverse populations, which mediate functions such as response to interferon gamma (IFNγ), innate immunity, T lymphocyte functions, and epidermal barrier dysfunctions (Table 1).”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [26]
A study with Mendelian randomization identified an association between age at onset of diabetes and also alcohol use with AD.
“A study with Mendelian randomization identified an association between age at onset of diabetes and also alcohol use with AD.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [26]
Cites
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing
Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., & Abecasis, G. R. (2012) · Nature Genetics · doi:10.1038/ng.2354 · Cited by 1,737 · see citing works
Biological interpretation of genome-wide association studies using predicted gene functions
Pers, T. H., Karjalainen, J. M., Chan, Y., Westra, H.-J., Wood, A. R., Yang, J., Lui, J. C., Vedantam, S., Gustafsson, S., Esko, T., et al. (2015) · Nature Communications · doi:10.1038/ncomms6890 · Cited by 787 · see citing works
Burgess, S., & Labrecque, J. A. (2018) · European Journal of Epidemiology · doi:10.1007/s10654-018-0424-6 · Cited by 569 · see citing works
Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology
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., et al. (2017) · Nature Genetics · doi:10.1038/ng.3985 · Cited by 550 · see citing works
Ishigaki, K., Akiyama, M., Kanai, M., Takahashi, A., Kawakami, E., Sugishita, H., Sakaue, S., Matoba, N., Low, S.-K., Okada, Y., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0640-3 · Cited by 508 · see citing works
A common variant on chromosome 11q13 is associated with atopic dermatitis
Esparza-Gordillo, J., Weidinger, S., Fölster-Holst, R., Bauerfeind, A., Ruschendorf, F., Patone, G., Rohde, K., Marenholz, I., Schulz, F., Kerscher, T., et al. (2009) · Nature Genetics · doi:10.1038/ng.347 · Cited by 317 · see citing works
Tylee, D. S., Sun, J., Hess, J. L., Tahir, M. A., Sharma, E., Malik, R., Worrall, B. B., Levine, A. J., Martinson, J. J., Nejentsev, S., et al. (2018) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32652 · Cited by 219 · see citing works
Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts
Paternoster, L., Savenije, O. E. M., Heron, J., Evans, D. M., Vonk, J. M., Brunekreef, B., Wijga, A. H., Henderson, A. J., Koppelman, G. H., & Brown, S. J. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2017.09.044 · Cited by 186 · see citing works
Replicated methylation changes associated with eczema herpeticum and allergic response
Boorgula, M. P., Taub, M. A., Rafaels, N., Daya, M., Campbell, M., Chavan, S., Shetty, A., Cheadle, C., Barkataki, S., Fan, J., et al. (2019) · Clinical Epigenetics · doi:10.1186/s13148-019-0714-1 · Cited by 28 · see citing works
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Update on the pathogenesis of atopic dermatitis.
Criado, P. R., Miot, H. A., Bueno-Filho, R., Ianhez, M., Criado, R. F. J., & de Castro, C. C. S. (2024) · Anais brasileiros de dermatologia · doi:10.1016/j.abd.2024.06.001 · Cited by 66 · see citing works
- Authors
- Chen, Y., & Chen, W.
- Affiliations
- Shenzhen Bay Laboratory (CN)
- Corresponding author
- Chen, Wenyan
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2022-11
- Volume
- 142
- Issue
- 11
- Pages
- 2958-2967.e8
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W4280496565
- Cited by
- 19
- References
- 9
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 1
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (217065/Z/19/Z)
- Medical Research Council (MC_PC_17228, MC_PC_15018, MC_PC_19009)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
- Keywords
- atopic dermatitis, genetic architecture, susceptibility genes, heritability, Mcl-1, drug-gene interactions, phenome-wide association study, Mendelian randomization, genetic correlation, immune system, multi-omics integration, treatment goals
- MeSH terms
- Dermatitis, Atopic, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Genomics, Genome-Wide Association Study, Mendelian Randomization Analysis, Myeloid Cell Leukemia Sequence 1 Protein
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