Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug-gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both the polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug repurposing opportunities that could improve lung function.
- Murray J Cairns
- Murray J Cairns
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The use of the Hunter Community Cohort data was approved by the University of Newcastle Human Ethics Research Committee (HREC, reference: H-820-0504a). All other information related to ethical approval for the individual GWAS studies we utilised in this study are detailed in their respective publications as referenced throughout the text
- Chris P Ponting, University of Edinburgh, United Kingdom
- Received: September 15, 2020
- Accepted: March 11, 2021
- Accepted Manuscript published: March 15, 2021 (version 1)
© 2021, Reay et al.
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