A Genomic Counseling Model for Population-Based Sequencing: A Pre-Post Intervention Study.

BACKGROUND: Novel uses of genome sequencing (GS) present an opportunity for return of results to healthy individuals, prompting the need for scalable genetic counseling strategies. We evaluate the effectiveness of a genomic counseling model (GCM) and explore preferences for GS findings in the general population. METHODS: Participants (N=466) completed GS and our GCM (digital genomics platform and group-based webinar), and indicated results preferences. Surveys were administered pre- (T0) and post- (T1) GCM. Change in knowledge and decisional conflict (DC) were evaluated using paired-sample T and Wilcoxon tests. Factors influencing knowledge and results preferences were evaluated using linear and logistic regression models. RESULTS: Participants were 56% female, 58% white, and 53% ≥40 years of age. Mean knowledge scores increased (Limitations: 3.73 to 5.63; benefits: 3.73 to 5.48, p<0.0001) and DC decreased (-21.9, p<0.0001) at T1 versus T0. Eighty-six percent of participants wished to learn all GS findings at T1 vs 78% at T0 (p<0.0001). Older age, negative/mixed attitudes toward genetics, and greater DC were associated with change in preferences post-intervention. CONCLUSION: In a population-based cohort undergoing GS interested in learning GS findings, our GCM increased knowledge and reduced DC, illustrating the GCM's potential effectiveness for GS counseling in the general population.

Genome screening, reporting, and genetic counseling for healthy populations.

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.

Genome Reporting for Healthy Populations-Pipeline for Genomic Screening from the GENCOV COVID-19 Study.

Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.