Dataset Information

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.

SUBMITTER: Casalino S

PROVIDER: S-EPMC9638226 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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

Casalino Selina S Frangione Erika E Chung Monica M MacDonald Georgia G Chowdhary Sunakshi S Mighton Chloe C Faghfoury Hanna H Bombard Yvonne Y Strug Lisa L Pugh Trevor J TJ Simpson Jared J Arnoldo Saranya S Aujla Navneet N Bearss Erin E Binnie Alexandra A Borgundvaag Bjug B Chertkow Howard H Clausen Marc M Dagher Marc M Devine Luke L Di Iorio David D Friedman Steven Marc SM Fung Chun Yiu Jordan CYJ Gingras Anne-Claude AC Goneau Lee W LW Kaushik Deepanjali D Khan Zeeshan Z Lapadula Elisa E Lu Tiffany T Mazzulli Tony T McGeer Allison A McLeod Shelley L SL Morgan Gregory G Richardson David D Singh Harpreet H Stern Seth S Taher Ahmed A Wong Iris I Zarei Natasha N Greenfeld Elena E Hao Limin L Lebo Matthew M Lane William W Noor Abdul A Taher Jennifer J Lerner-Ellis Jordan J

Human genetics 20221104 2

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 d ...[more]

PMID: 36331656

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Project description: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.

Project description:Studies suggest that 1-3% of the general population in the United States unknowingly carry a genetic risk factor for a common hereditary disease. Population genetic screening is the process of offering otherwise healthy patients in the general population testing for genomic variants that predispose them to diseases that are clinically actionable, meaning that they can be prevented or mitigated if they are detected early. Population genetic screening may significantly reduce morbidity and mortality from these diseases by informing risk-specific prevention or treatment strategies and facilitating appropriate participation in early detection. To better understand current barriers, facilitators, perceptions, and outcomes related to the implementation of population genetic screening, we conducted a systematic review and searched PubMed, Embase, and Scopus for articles published from date of database inception to May 2020. We included articles that 1) detailed the perspectives of participants in population genetic screening programs and 2) described the barriers, facilitators, perceptions, and outcomes related to population genetic screening programs among patients, healthcare providers, and the public. We excluded articles that 1) focused on direct-to-consumer or risk-based genetic testing and 2) were published before January 2000. Thirty articles met these criteria. Barriers and facilitators to population genetic screening were organized by the Social Ecological Model and further categorized by themes. We found that research in population genetic screening has focused on stakeholder attitudes with all included studies designed to elucidate individuals' perceptions. Additionally, inadequate knowledge and perceived limited clinical utility presented a barrier for healthcare provider uptake. There were very few studies that conducted long-term follow-up and evaluation of population genetic screening. Our findings suggest that these and other factors, such as prescreen counseling and education, may play a role in the adoption and implementation of population genetic screening. Future studies to investigate macro-level determinants, strategies to increase provider buy-in and knowledge, delivery models for prescreen counseling, and long-term outcomes of population genetic screening are needed for the effective design and implementation of such programs. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020198198.

Project description:The South Carolina cystic fibrosis (CF) newborn screening (NBS) program changed in 2019 to include CFTR genotyping for babies with top 4% immunoreactive trypsinogen, which improves sensitivity and timeliness but increases carrier detection. Carrier identification has genetic implications for the family and parents of NBS+ babies have increased emotional distress. Genetic counseling (GC) may increase parent understanding and reduce anxiety yet is not uniformly offered at CF centers. We report our early results after implementing GC for NBS+ families at the time of sweat chloride testing based on GC availability, which resulted in an unselected GC- control arm. Sixteen mothers (GC+ = 9, GC- = 7) participated in an online survey about their experience. Responses were analyzed in aggregate and for differences between GC+ and GC- groups. All-respondent sadness and anxiety increased with notification of the NBS+ result and decreased after sweat test results. Anxiety and sadness were greater in GC- compared to GC+ until after the diagnosis was resolved, though emotional differences between the groups were not statistically significant. On a scale of 0 = not at all to 10 = extremely, GC was rated very helpful (mean 9.0, range 5-10), informative (mean 8.9, range 4-10), comforting (mean 9.1, range 6-10), and minimally distracting (mean 1.8, range 0-9). All participants correctly identified that a risk for a child to have CF exists when both parents are (at least) carriers. Delivery of NBS results to respondents varied by timing, informant, and information given. The child's pediatrician notified 10 (62.5%) of the NBS+ result. Parents felt they were notified in a timely manner (68.8%), by someone knowledgeable about NBS (62.5%), the sweat test (62.5%), CF (43.8%), and genetics (43.8%) and who cared about them (81.3%). Parents felt worried (81.3%), confused (81.3%), empowered (25%), and other (sad, shocked, scared, overwhelmed, devastated, defeated). Data from this single-center study suggest benefit of GC, that families would value earlier contact with an expert, and that prompt diagnostic resolution may reduce duration of parental distress.

Dataset Information

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

Publications

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

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