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Asthma severity, nature or nurture: genetic determinants
Current Opinion in Pediatrics
|May 16, 2019
Summary
Genetic factors influence severe asthma, with recent studies identifying 25 associated loci. Future research will focus on rare genetic variations and gene-environment interactions for severe asthma.
Area of Science:
- Genetics
- Pulmonology
- Asthma Research
Background:
- Twin studies suggest genetic factors contribute to 25% of asthma severity variability.
- Previous genetic association studies for asthma severity were often underpowered.
- Distinguishing asthma severity variants from susceptibility variants remains a challenge.
Purpose of the Study:
- To review the progress in identifying genetic determinants of severe asthma.
- To highlight recent findings from large-scale genetic association studies.
- To discuss implications for future research directions.
Main Methods:
- Review of existing literature on genetic determinants of asthma severity.
- Analysis of findings from genome-wide association studies (GWAS).
- Consideration of insights from rare monogenic disorders associated with severe asthma.
Main Results:
- A recent GWAS in over 57,000 individuals identified 25 significant loci associated with asthma severity.
- Three novel loci (GATA3, MUC5AC, KIAA1109) were found to be associated with asthma severity.
- Loss-of-function variants in the filaggrin gene are consistently linked to more severe asthma outcomes.
Conclusions:
- Severe asthma is a complex polygenic trait.
- Future research should investigate rare genetic variations.
- Gene-by-environment interactions are crucial for understanding severe asthma.
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