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Discovering metabolite quantitative trait loci in asthma using an isolated population
Randi K Johnson1, Tonya Brunetti1, Kevin Quinn2
1Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo.
The Journal of Allergy and Clinical Immunology
|November 15, 2021
Summary
This study integrated metabolomics and genetics to uncover new asthma genetic effects. We identified genetically driven metabolites, offering insights into asthma
Area of Science:
- Genetics and Genomics
- Metabolomics
- Asthma Research
Background:
- Metabolomics integration with genetics can advance disease pathogenesis understanding.
- Asthma genetic studies have underutilized this integrated approach.
Purpose of the Study:
- Discover novel genetic effects in asthma.
- Characterize molecular consequences of asthma genetic risk by integrating metabolomics.
- Focus on a homogeneous population for robust findings.
Main Methods:
- Quantified 2612 serum metabolites using untargeted metabolomics in 348 residents.
- Performed genome-wide association studies (GWAS) on heritable, asthma-associated metabolites.
- Utilized colocalization analysis to identify shared genetic signals between metabolites and asthma.
Main Results:
- 60 metabolites associated with asthma (P < .01), including 40 heritable ones.
- Strong association for endocannabinoid linoleoyl ethanolamide with VNN1 on chromosome 6.
- Evidence of shared causal variants between 3 metabolites (e.g., acisoga, leukotriene B4) and asthma.
Conclusions:
- Identified novel metabolite quantitative trait loci associated with asthma.
- Characterization of genetically driven metabolites provides insight into functional consequences of asthma genetic risk factors.
