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”).