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Asthma Genetics in the Post-GWAS Era.
1Department of Human Genetics, University of Chicago, Chicago, Illinois.
Annals of the American Thoracic Society
|March 31, 2016
Summary
Genome-wide association studies (GWAS) have identified asthma risk alleles, but their small effect sizes limit understanding. Future research should focus on gene expression variations and cell models for a complete genetic picture of asthma.
Area of Science:
- Genetics
- Genomics
- Asthma Research
Background:
- Genome-wide association studies (GWAS) have identified numerous genetic loci associated with asthma.
- However, identified asthma risk alleles have small effect sizes, explaining limited disease prevalence.
- Significant challenges remain in the post-GWAS era for understanding complex genetic architectures.
Purpose of the Study:
- To review the limitations of current GWAS approaches for asthma.
- To propose alternative strategies for characterizing the genetic architecture of asthma.
- To highlight the importance of gene expression and gene-environment interactions in asthma genetics.
Main Methods:
- Review of existing literature on GWAS for asthma.
- Discussion of challenges in post-GWAS genetic research.
- Proposal of focusing on genetic variations influencing gene expression.
- Emphasis on utilizing cell models for gene-environment interaction studies relevant to asthma.
Main Results:
- GWAS have identified novel asthma risk alleles and loci.
- Small effect sizes of identified alleles limit their contribution to asthma prevalence.
- Current GWAS approaches face limitations in fully explaining asthma's genetic basis.
Conclusions:
- Alternative strategies are needed to overcome GWAS limitations in asthma research.
- Focusing on genetic variations impacting gene expression is a promising direction.
- Cell-based models of gene-environment interactions are crucial for a comprehensive understanding of asthma genetics.
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