The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank
Open accessAbstract
Background: Clinical and epidemiological studies have shown that obesity is associated with asthma and that these associations differ by asthma subtypes. Little is known about the shared genetic components between obesity and asthma. Objective: To identify shared genetic associations between obesity-related traits and asthma subtypes in adults. Methods: A cross-trait genome-wide association study (GWAS) was performed using 457,822 individuals of European ancestry from the UK Biobank. Experimental evidence to support the role of genes significantly associated with both obesity-related traits and asthma via GWAS was sought using results from obese vs. lean mouse RNA-seq and RT-PCR experiments. Results: We found a substantial positive genetic correlation between BMI and later-onset asthma defined by asthma age of onset at 16 years of age or older (Rg =0.25, P=9.56×10−22). Mendelian Randomization analysis provided strong evidence in support of BMI causally increasing the risk of asthma. Cross-trait meta-analysis identified 34 shared loci among 3 obesity-related traits and 2 asthma subtypes. GWAS functional analyses identified potential causal relationships between the shared loci and GTEx tissue eQTLs, shared immune- and cell differentiation-related pathways between obesity and asthma. Finally, RNA-seq data from lungs of obese versus control mice found that two genes (ACOXL and MYL6) from the cross-trait meta-analysis were differentially expressed, and these findings were validated by RT-PCR in an independent set of mice. Conclusions: Our work identified shared genetic components between obesity-related traits and specific asthma subtypes, reinforcing the hypothesis that obesity causally increases the risk of asthma, and identifying molecular pathways that may underlie both obesity and asthma.
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Self-citationAn atlas of genetic correlations across human diseases and traits
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Self-citationMixed-model association for biobank-scale datasets
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Metadata
- Authors
- Zhu, Z., Guo, Y., Shi, H., Liu, C.-L., Panganiban, R. A., Chung, W., O'Connor, L. J., Himes, B. E., Gazal, S., Hasegawa, K., Camargo, C. A., Qi, L., Moffatt, M. F., Hu, F. B., Lu, Q., Cookson, W. O. C., & Liang, L.
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 145
- Issue
- 2
- Pages
- 537-549
- ISSN
- 0091-6749 (ISSN-L)
- OpenAlex
- W2981587292
- Cited by
- 362
- References
- 15
- FWCI
- 20.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Zhu, Z., Guo, Y., Shi, H., Liu, C.-L., Panganiban, R. A., Chung, W., O'Connor, L. J., Himes, B. E., Gazal, S., Hasegawa, K., Camargo, C. A., Qi, L., Moffatt, M. F., Hu, F. B., Lu, Q., Cookson, W. O. C., & Liang, L. (2020). Shared genetic and experimental links between obesity-related traits and asthma subtypes in UK Biobank. Journal of Allergy and Clinical Immunology. https://doi.org/10.1016/j.jaci.2019.09.035
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