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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
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Functional Variant Discovery Identifies a Novel Genetic Link between SPRY2, Wood Smoke, and Asthma
Arnav Gupta1,2, Amber Dahlin3, Alejandra Macario1
1Department of Medicine and.
American Journal of Respiratory Cell and Molecular Biology
|September 29, 2025
Summary
Wildfire smoke exposure increases asthma risk. Researchers found specific genetic variants, like rs3861144 affecting SPRY2, that influence how airway cells respond to wood smoke particles (WSP), offering new insights into asthma development.
Area of Science:
- Environmental Health
- Genetics
- Pulmonology
Background:
- Climate change and land use policies drive increased wildfire smoke.
- Wildfire smoke's impact on asthma is known, but genetic factors and molecular mechanisms remain unclear.
- This knowledge gap limits identifying high-risk individuals and developing targeted interventions.
Purpose of the Study:
- To identify genetic risk variants associated with asthma and wood smoke particle (WSP) exposure.
- To investigate the molecular mechanisms by which WSP influences asthma risk.
- To explore potential genetic biomarkers for asthma risk assessment.
Main Methods:
- Utilized the Genetic Epidemiology Research on Aging (GERA) cohort to identify genetic variants.
- Colocalized genetic risk variants with genomic responses to wood smoke particles (WSP).
- Tested allele-dependent transcriptional regulatory function of prioritized variants in airway epithelial cells.
Main Results:
- Identified 52 genetic risk variants associated with asthma and WSP exposure.
- The rs3861144 variant in SPRY2 demonstrated allele-dependent changes in response to WSP.
- These changes involved Interleukin-8 secretion, ERK activation, and cellular repair mechanisms.
Conclusions:
- Wildfire smoke particles (WSP) influence asthma risk through specific molecular pathways.
- The rs3861144 variant and SPRY2 gene are implicated in WSP-mediated asthma risk.
- Genetic candidates identified may serve as clinical tools for asthma risk stratification.
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