Predicting Response to Short-Acting Bronchodilator Medication Using Bayesian Networks

Abstract

Aims: Bronchodilator response tests measure the effect of β₂-agonists, the most commonly used short-acting reliever drugs for asthma. We sought to relate candidate gene SNP data with bronchodilator response and measure the predictive accuracy of a model constructed with genetic variants. Materials & methods: Bayesian networks, multivariate models that are able to account for simultaneous associations and interactions among variables, were used to create a predictive model of bronchodilator response using candidate gene SNP data from 308 Childhood Asthma Management Program Caucasian subjects. Results: The model found that 15 SNPs in 15 genes predict bronchodilator response with fair accuracy, as established by a fivefold cross-validation area under the receiver-operating characteristic curve of 0.75 (standard error: 0.03). Conclusion: Bayesian networks are an attractive approach to analyze large-scale pharmacogenetic SNP data because of their ability to automatically learn complex models that can be used for the prediction and discovery of novel biological hypotheses.

KEYWORDS::

• asthma
• Bayesian networks
• β₂-agonists
• bronchodilator response
• prediction

Acknowledgments

We thank all CAMP subjects for their ongoing participation in this study.

Financial & competing interests disclosure

We acknowledge the CAMP investigators and research team, supported by the National Heart, Lung and Blood Institute (NHLBI), for collection of CAMP Genetic Ancillary Study data. All work on data collected from the CAMP Genetic Ancillary Study was conducted at the Channing Laboratory of the Brigham and Women‘s Hospital under appropriate CAMP policies and human subject‘s protections. The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, and P01 HL083069 from the NHLBI, NIH. Support for BEH was provided by 2T15LM007092–16, National Library of Medicine, NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

We acknowledge the CAMP investigators and research team, supported by the National Heart, Lung and Blood Institute (NHLBI), for collection of CAMP Genetic Ancillary Study data. All work on data collected from the CAMP Genetic Ancillary Study was conducted at the Channing Laboratory of the Brigham and Women‘s Hospital under appropriate CAMP policies and human subject‘s protections. The CAMP Genetics Ancillary Study is supported by U01 HL075419, U01 HL65899, and P01 HL083069 from the NHLBI, NIH. Support for BEH was provided by 2T15LM007092–16, National Library of Medicine, NIH. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.