Findings from comprehensive genome sequencing in the Canadian population: Results from the GENCOV Study

Purpose: Opportunistic genome sequencing (GS) allows for the return of findings to clinical and research cohorts. We report on comprehensive GS results from the GENCOV study in Ontario, Canada. Methods: GS data were analyzed for clinically significant variants associated with monogenic disease and carrier status for autosomal recessive and X-linked conditions, pharmacogenomic variation, polygenic risk scores for common conditions, human leukocyte antigen and blood group genotypes, and genetic ancestry. GS results were summarized using descriptive statistics. Results: GS was completed on 1292 participants; 53% were female, 53% were 18 to 39 years old, and 816 (63%) were estimated to have European genetic ancestry. All (100%) had a variant associated with drug metabolism, 845 (65%) with increased polygenic risk scores, 735 (57%) with a risk-associated human leukocyte antigen genotype, and 857 (69%) and 91 (7%) with a rare red blood cell and/or platelet antigen, respectively. Of 851 who received reports, 261 (31%) had a variant associated with monogenic disease (178 or 21% were considered medically actionable) and 782 (92%) had at least one variant associated with carrier status. Conclusion: Opportunistic GS demonstrated that many individuals harbor GS findings impacting their health, illustrating the potential of GS to inform personalized and proactive health care for Canadians.