Purpose: Population-based genomic screening (PGS) offers significant public health potential by identifying individuals at risk for clinically actionable genetic conditions. While existing frameworks guide gene selection based on clinical actionability, defining programmatic considerations, including ethical, economic, and equity-related factors, is necessary to support population-level implementation. This review aims to develop a set of programmatic considerations to guide PGS implementation decisions. Methods: Using a structured, three-step deliberative process aligned with development of the Clinical Genome Resource (ClinGen) PGS Actionability Framework, multidisciplinary experts in public health genomics, clinical genetics, genetic counseling, ethics, health economics, and implementation science identified and refined key programmatic domains relevant to PGS implementation. Results: Eight programmatic consideration domains were identified: (1) Program Evaluation, (2) Justice, (3) Feasibility, (4) Acceptability, (5) Respect for Autonomy, (6) Population-Level Costs, (7) Analytic Validity/Test Performance, and (8) Program Management. Each domain was defined and accompanied by guiding questions to support implementation planning, addressing critical gaps by incorporating population-level concerns such as equity, sustainability, and public trust. Conclusion: These programmatic considerations provide essential contextual guidance to support ethical and effective implementation of PGS programs. Used alongside gene-level actionability frameworks, they can inform how screening programs are designed, operationalized, and evaluated to better align genomic medicine with population health priorities.
Background: Currently, prostate-specific antigen (PSA) testing remains the most important tool for prostate cancer (PCa) screening, yet it does not fully inform on personal risk level. Therefore, we collected information on screening behavior, family history, and polygenic risk score (PRS) from unaffected men to assess the association among PCa screening behavior, family history, and PRS. Methods: We collected past screening behavior, family history, and self-estimated risk information using a structured questionnaire, and saliva samples to generate PRS. Genotyping was conducted using the Illumina Oncoarray assay using saliva DNA. We investigated relationships among PCa screening behavior, family history, and PRS. Results: PRS information was generated from 76 unaffected men recruited from various community settings. Among 53 African American (AA) men, 13/53 (24.5%) were in the low-risk category (<30 percentile), and 17/53 (32%) were in the high-risk category (>70 percentile). In comparison, 21/23 (91%) of European American (EA) participants were in the low-risk category, and none of EA participants were in the high-risk category. AA men had a significantly higher PRS for PCa than EAs (p<0.001). Three variables (i.e., age, family history, and PRS) were significantly associated with prior PCa screening behaviors. Discussion: This study suggested differential genetic risk levels between racial groups. Men with a high risk of PCa could benefit from informed discussions around the risks and benefits of available options for PCa screening, especially among AA men. PRS information may assist AA men and clinicians in shared and informed decision-making discussions for routine PSA screening.
Sudden Arrhythmia Death Syndromes are a group of heritable genetic conditions that confer risk of sudden cardiac arrest or sudden cardiac death (SCA/SCD) in young, seemingly healthy individuals. Appropriate diagnosis of an SCA/SCD condition allows for guided management and prevents future sudden cardiac arrest and/or death from occurring. However, identification of a genetic predisposition can affect future insurance applications. While the United States’ 2008 Genetic Information Non-discrimination Act (GINA) provides protection against genetic discrimination in employment and health insurance, it does not protect against the use of genetic information with regards to life insurance. This study aimed to expand the current understanding of life insurance experiences in the hereditary SCA/SCD community, gather strategies for individuals who wish to attain life insurance, and facilitate the development of life insurance specific patient and provider resources. Participants were recruited through The Sudden Arrhythmia Death Syndromes (SADS) Foundation. Semi-structured interviews were completed with 15 participants who have or are at-risk for SCA/SCD. Thematic analysis captured three themes: Emotional Outlook and Impact, Navigating the System, and Pay It Forward. Our participants with or at-risk for SCA/SCD expressed interest in attaining life insurance coverage that meets their individual needs and invested a meaningful amount of time and effort into their attempts. Most were unsuccessful. They perceived a lack of understanding regarding heritable SCA/SCD conditions by insurance professionals and felt their denials were unfairly attributed to their SCA/SCD diagnosis. Participants shared numerous suggestions for improved approaches to life insurance attainment and educational opportunities.
