History of respiratory Genetics: Key Canadian contributions

The identification of genetic determinants in respiratory diseases in Canada has evolved significantly over the past few decades. Research in Canada has played an important role in contributions to human genetics. Early breakthroughs emerged from research on cystic fibrosis, which is a disease with high prevalence in the Canadian population. In 1989, the CFTR gene was discovered through linkage analysis and positional cloning by researchers led in part by Canadian scientists. This important discovery established Canada as a global leader in monogenic disease research and provided insight for subsequent genetic studies. Asthma is a heritable but genetically complex disease and Canadian cohorts enabled early candidate gene studies, followed by genome-wide association studies (GWAS). These studies identified common variants near ORMDL3, IL33 and IL1RL1, among several other genes and demonstrated the polygenic nature of asthma with the importance of environmental interactions. More recently, Canadian cohort initiatives have integrated multi-omics and multi-ancestry data to improve the prediction of asthma susceptibility. In chronic obstructive pulmonary disease (COPD), Canadian studies characterized gene-environment interactions such as tobacco smoke and occupational exposures. Research has identified a rare monogenic form such as alpha-1 antitrypsin deficiency (SERPINA1), while GWAS discovered additional loci CHRNA3/CHRNA5, HHIP and FAM13A. Large Canadian longitudinal cohorts now facilitate the study of COPD and help guide earlier diagnosis, targeted therapies and prevention strategies. Together, these advances show how Canadian research has progressed from single-gene discovery to large-scale, high-throughput genomic approaches to support more personalized and precise care for respiratory diseases.