Comprehensive Genome Report
A comprehensive genomic report was developed for return of results through the GENCOV study. The report sections, including SF from GS and additional research findings, are summarized in Figure 2. A mock example of a complete report can be viewed in Supplementary File 5.
The first page of the report states the participant’s elected SF categories and provides a concise summary of the genomic findings. Pathogenic and likely pathogenic variants associated with personal disease risks and reproductive planning are presented in a table format that includes the gene and transcript, variant coding and protein change, zygosity, associated disease, inheritance pattern, control population frequency and variant classification. Detailed variant interpretations, as well as specific disease information and familial risk are provided. Recommendations are made for genetic counseling and clinical follow-up of research results. Likely benign, benign and variants of uncertain significance were not included in the report.
Variants in genes with established evidence at the time of analysis (PharmGKB levels 1A and CPIC levels A) for altered drug metabolism are reported. The gene name, genotype, rsID, medications, and metabolizer phenotype are included for non-normal metabolizer phenotypes (e.g. poor or rapid metabolizer). An expanded pharmacogenomics table with specific implications and dosing recommendations, as well as general information on gene-medication interactions is provided in the appendix.
PRS for common health conditions are reported dichotomously as an “average” or “increased” polygenic risk for disease. An increased polygenic risk is equivalent to a greater than 2-fold increased risk for the condition. PRS results are supplemented with information on the general population lifetime risk and a description of the condition, as well as an appendix with additional resources for participants including informational websites and suggestions for lifestyle modifications that may help to mitigate risk.
The participant’s predicted HLA genotype (e.g. HLA-A*03:01) is provided and known autoimmune disease associations are indicated based on HLA type where applicable. If there are no known disease associations for the participant’s HLA genotype they are considered “average risk.” If the participant has an HLA genotype with a known disease association, the table will include an “increased” risk for the associated disease along with evidence from the literature (sample size and OR) and a brief description of the disease. Blood group genotyping includes the participant’s ABO blood type and Rhesus (Rh) antigen in addition to expanded genotyping, which includes rare red blood cell antigens (e.g. KDAS+) and human platelet antigens. Reports indicate the relevance of HLA and blood group type to COVID-19 susceptibility and outcomes, as well as blood product donation and transfusions. Links are provided to external resources for rare blood type registration and stem cell donation in Canada.
The top ten ancestry associations are reported in the form of a color-coded pie chart with percentage values representing each population group. The chart is accompanied by a legend that defines the population group name and associated color. The majority of the participant’s estimated genetic ancestry is clearly stated above the figure (e.g. “By looking at multiple genetic changes present in your DNA, we estimate the majority of your genetic ancestry to be Chinese”).