Genome screening, reporting, and genetic counseling for healthy populations

Abstract

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

Fig. 1

Workflow for genetic counseling and return of GS results through the GENCOV study. (1) Study participants complete an online intake survey to collect information on medical history and COVID-19 symptoms, as well as an educational digital genomics platform wherein they are able to indicate initial preferences for return of SF from GS. The participant completes pre-test counseling with the study GC, either in group format by teleconference or by personal telephone and/or video appointment. The study GC confirms and records participants’ preferences for SF from GS. (2) GS data are filtered and analyzed based on participant preferences. A final GS report is compiled and reviewed by the study team. (3) The GC and Geneticist meet to review reports to determine which participants require results counseling and clinical follow-up. Individuals with clinically significant findings meet with the study GC (and Geneticist, where applicable) by teleconference to discuss their results and the plan for follow-up. The GC writes the consultation letter and initiates clinical referral(s). The family physician is forwarded a copy of the report, letter, and referrals with participants’ consent. Result counseling appointments and referrals are not initiated for other findings; however, participants will receive a copy of their report along with a letter summarizing their results with the option to speak with the study GC if they have questions about their report. †Clinically significant findings include monogenic disease risks for rare Mendelian conditions as well as medically actionable conditions. Other findings include carrier status results, PRS for common conditions, pharmacogenomics, ancestry, HLA blood group, and viral lineage, GC Genetic counselor, SF Secondary findings, GS Genome sequencing

Fig. 2

Summary of the elements of the comprehensive GS report: (1) Clinically significant findings related to the participant’s risk for hereditary conditions (monogenic disease risks, including medically actionable and rare Mendelian conditions); (2) findings relevant to reproductive planning (carrier status); (3) pharmacogenomic variants; (4) PRS for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group genotype; (8) COVID-19 viral lineage; (9) testing methodologies and limitations; and (10) informational appendices. PRS Polygenic risk score, Rh Rhesus, GS Genome sequencing, HLA Human leukocyte antigen