Introduction: Most studies of family communication about inherited risk of hereditary breast and ovarian cancer syndrome are conducted in high-risk clinic settings and show that cancer patients are highly selective in sharing inherited risk information. The reasoning processes behind this are not well understood and yet to be explored in population-based samples. Methods: We conducted a secondary analysis of ovarian cancer survivors participating in the Your Family Connects communication intervention. Website use data were analyzed to assess survivors’ choices of at-risk relatives for contact (i.e., total number and relationship). Retrospective online think-aloud interviews explored the decision-making processes driving which relatives were included or excluded. Results: The 116 participants enumerated 164 relatives (mean = 1.41; mode = 0; range = 0 to 7). Approximately one-third of them (45/116, 38.8%) did not enumerate any relatives. Most of the participants who identified relatives (71/116) identified female relatives (95 women vs. 30 men in first-degree relatives; 29 women and 10 men in second-degree relatives). When survivors were asked to deliberate about their enumeration behaviors, they described making heuristic-based judgments about which relatives would be most likely to follow through on genetic counseling. Survivors considered that female relatives would have the most to gain, but the relatives’ age and the extent of emotional closeness were also important in the decision-making process. Conclusion: Future research is needed in population-based samples to understand these qualitative drivers and consider decision-aid strategies to help cancer patients consider options for communication that are sensitive to the multifactorial context of at-risk relatives’ lives.
PURPOSE:Clinical applications of epigenetic technologies could revolutionize precision medicine. However, successful uptake in clinical settings may be influenced by public opinion. We investigated public beliefs about possible benefits and drawbacks of epigenetic-based medical technologies. METHODS:We recruited 153 adults from across the United States to participate in one of 27 virtual focus groups, each lasting 45-75 mins. Groups were stratified by education (less than bachelor's degree vs. bachelor's degree or more) and race and ethnicity (Black/African American, Asian, Indigenous [Native Hawaiian/Pacific Islander, American Indian/Alaska Native], Hispanic, and white). Participants viewed an educational video about epigenetics prior to discussion. We used inductive and deductive qualitative content analysis. RESULTS:Participants indicated that epigenetic technologies could be used to guide risk-stratified prevention (i.e., engage in behaviors to reduce the risk of developing a health condition; engage in screening and early-detection behaviors to enable early treatment; facilitate clinical history-taking; inform reproductive planning decisions) and to develop novel therapeutics and editing approaches (i.e., new medications; epigenetic editing). However, participants also mentioned concerns about the ethical, legal, and social implications (ELSI) of epigenetics, including: exacerbating health disparities; the high cost of treatment and health insurance; promoting eugenics; and epigenetic-based discrimination by healthcare providers. Each of the race, education, and ethnicity strata included content related to each of the three major subthemes of risk-stratified prevention, novel therapeutics, and ELSI considerations. DISCUSSION:Efforts to translate basic epigenetics research to clinical practice hold promise, but it is also critical to create solutions that address people's concerns.
BACKGROUND:Familial hypercholesterolemia (FH) is a common, autosomal dominant genetic disorder characterized by lifelong elevations in low-density lipoprotein cholesterol and a markedly increased risk of premature atherosclerotic cardiovascular disease. Despite a well-defined genetic architecture, highly effective therapies, and strong evidence demonstrating the benefits of early identification and treatment, FH has historically remained underdiagnosed and undertreated worldwide. This persistent gap highlights broader challenges in translating genomic discovery into measurable population health impact. SUMMARY:In this review, we examine how initiatives led by the Centers for Disease Control and Prevention, the Family Heart Foundation, and other stakeholders have advanced awareness, case identification, surveillance, evidence-based care, and implementation of genomic medicine in cardiovascular disease prevention. Using the framework of the Essential Public Health Services - assessment, policy development, and assurance/implementation - we evaluate progress achieved, identify implementation barriers, and highlight opportunities and recommendations to strengthen the population-level impact of FH detection, treatment, and prevention efforts. KEY MESSAGES:The FH experience provides valuable lessons for other genomic conditions, demonstrating that achieving public health benefit requires more than scientific discovery. Greater investment in implementation science, a continued focus on health equity, and sustained systems-level engagement will be essential to translate genomic knowledge into durable and scalable improvements in population health.
Introduction: The diagnostic journey for rare diseases (RDs) often involves lengthy delays and significant burdens on patients and their families. Genetic newborn screening (NBS) for RDs offers a potential opportunity for early diagnosis and treatment. This study explores factors influencing parental decisions regarding participation in genetic NBS for RDs in two European countries (Italy and Germany). Methods: This mixed-methods qualitative study is composed of focus group discussions and ranking exercises. It was conducted with parents seeking genetic testing (n = 5) and expectant parents from the general population (n = 11). All participants were recruited in spring 2024 in Germany and winter 2024 in Italy via contacts from genetic centres and obstetric services. Thematic analysis was performed by two independent coders to identify main themes and subthemes. Results: Three key themes were identified: (1) the complexity of the decision-making process, (2) the importance of certainty and disease characteristics, and (3) the anticipation of negative consequences. Participants trusted healthcare professionals to guide their decisions, also emphasizing the need for extensive education and comprehensive support systems. Concerns about test accuracy, potential psychological impact of uncertain or positive results, and anticipated social implications were also reported. Conclusion: These findings highlight the nuanced considerations surrounding the implementation of genetic NBS for RDs and the necessity of addressing parental experiences in clinical practice and policy development. Participants emphasized the importance of accessible education and clear communication, the support of trusted healthcare professionals and that ethical reflection is essential for the equitable integration of genetic NBS into newborn care.
Introduction: Improving access to genetic testing has increased the number of individuals identified with cancer genetic predisposition. Hereditary Breast and Ovarian Cancer (HBOC) and Lynch syndrome (LS) are key examples of high-risk hereditary cancer syndromes. Ensuring that carriers of germline pathogenic/likely pathogenic variants (GPVs) receive evidence-based risk counseling, surveillance and risk-reducing interventions remains a global challenge. Variations in implementation and reporting of international guidelines across healthcare systems contributes to this problem. Methods: An international workshop on cancer genetic care held from March 12–15 2025 in Switzerland brought together 40 experts on this topic from 10 countries. The workshop combined evidence-based presentations with expert-led discussions and considered novel strategies, which were synthesized in key discussion points. Results: Participants highlighted major inconsistencies in reporting age of initiation and uptake of surveillance, follow-up intervals, and uptake of risk-reducing interventions for carriers of GPV associated with genetic predisposition to cancer between and within countries. These differences are due to variations in available technology, insurance coverage, and sociocultural attitudes that shape national clinical guidelines. Participants emphasized the need for a standardized approach for reporting surveillance practices, including clear definitions of gene-specific recommendations, timing of follow-up, and alternatives when ideal resources are limited. In addition to these reporting issues, participants also noted the need for sustained outreach for lifelong follow-up surveillance of GPV carriers through digital as well as low-tech approaches. Conclusion: Standardized reporting of surveillance and risk-reducing practices across countries may improve the quality and comparability of data in cancer genetic predisposition, reveal gaps in genetic care, and inform outreach strategies for engaging GPV carriers in lifelong cancer risk management.
Introduction: Technical advances and decreasing costs of next-generation sequencing have generated global interest in its potential for newborn screening (NBS). Genomic NBS (gNBS) enables the expansion of detectable conditions as a first-tier test and can improve screening accuracy as a second-tier test. A shared vision among all involved stakeholders is essential to guide the next steps for gNBS in public health programs. Methods: A Dutch stakeholder workshop on gNBS was organized and attended by 56 participants from different fields, including clinical care, genetics, research, and NBS. The workshop aimed to inform about developments, identify challenges, foster connections, and build a shared vision. Based on the workshop outcomes, recommended next steps were formulated to support policy and practice decision-making for the integration of genomics into NBS. Results: Six key themes were identified from the workshop data: (1) expansion of the scope of NBS with genomics, (2) clinical aspects, (3) technical and workflow feasibility, (4) data storage and privacy issues, (5) information provision and consent, and (6) stakeholder roles and responsibilities. Participants highlighted challenges for gNBS, including reaching consensus on scope definition, systematic gene selection, standards for variant reporting, the large data volume, the complexity of information provision, and the current representation of stakeholders in NBS. Conclusion: The recommended next steps, derived from stakeholders’ perceived challenges and considerations, reflect the complex and interconnected nature of integrating genomics into NBS, emphasizing the importance of alignment and coordination across disciplines. Translating these recommendations into public health NBS practice requires strong stakeholder engagement and enhanced multidisciplinary collaboration.
Introduction: Familial hypercholesterolemia (FH) is a common autosomal dominant genetic disorder conferring a high risk of premature atherosclerotic cardiovascular disease (ASCVD), without early diagnosis and treatment. Underdiagnosis remains a major public health problem; cascade testing (systematically identifying blood relatives) can mitigate this burden. The Identification Methods, Patient Activation, and Cascade Testing for FH (IMPACT-FH, 5R01HL148246-04) study evaluated family communication strategies for FH cascade testing and significantly increased uptake in a population genomic screening setting. The current IMPACT-FH Renewal (2R01HL148246-05) will next adapt these strategies to individuals diagnosed with FH outside of population genomic screening, evaluate the cost and performance of detection strategies within health systems, and define elements that help sustain FH screening programs. Methods: A pragmatic trial guided by the Conceptual Model of Implementation Research will be conducted to evaluate generalized family communication strategies to facilitate FH cascade testing in primary care (aim 1). We will apply economic evaluation modeling methods to compare implementation costs, efficiency, and performance of FH implementation strategies and develop a generic modeling tool for other healthcare systems to support local decision-making (aim 2). We will use a convergent mixed-methods approach guided by the Integrated Sustainability Framework to understand factors influential in sustaining FH screening programs at an international level (aim 3). Conclusion: By addressing novel communication strategies, economic impact, and sustainability of FH cascade testing, this study seeks to develop generalizable approaches to improving identification of FH to reduce the high burden of FH-associated ASCVD.
Introduction: Relatives of a victim of sudden cardiac death in the young (SCDY) may be at-risk for hereditary cardiomyopathies and arrhythmias; effective communication of cardiac risk is imperative. Family leaders are often responsible for communicating risk to surviving family during a difficult time. Cascade screening uptake is low among at-risk family members; identifying barriers of risk communication can help improve strategies. Purpose: Explore barriers and facilitators to communication about cascade screening in families who have lost a family member to SCDY. Methods: Semi-structured interviews (n = 14) were conducted with family members of a SCDY decedent. Participants were recruited from the Sudden Arrhythmia Death Syndrome advocacy group. Interviews explored the facilitators, challenges and proposed interventions at different stages of risk communication. Interviews were conducted until data saturation was reached. Interviews were audio recorded, transcribed, and analyzed using conventional content analysis. Results: Five categories were identified from the interviews: 1. Participants understood fundamental risks but the clinical variability in arrhythmia and cardiomyopathy was difficult to interpret and convey; 2. Family leaders felt some family disregarded risk information; 3. Grief interfered with family leader’s ability to understand and communicate risk information; 4. Communication aids were insufficient stand-alone interventions; 5. Families advocated for a “genetic family navigator”. Conclusion: This is the first study to evaluate cardiac risk communication between adult family members after a SCDY. Five categories provide practical strategies to improve clinical care and communication for families after SCDY and emphasize the need for genetic family navigators to facilitate cascade screening.
INTRODUCTION:Professional societies recommend pediatric genetic testing only when results may impact medical management in childhood. However, with increasing access to genetic information in various settings, young people's responses to learning pathogenic or likely pathogenic (P/LP) genetic results remain understudied. METHODS:The Engaging Adolescents in Decisions about Return of Genomic Research Results clinical trial enrolled 483 adolescents and young adults (ages 13-21 years) who made decisions about whether to undergo prospective genomic screening to learn their personal results related to 32 sets of treatable, preventable, and adult-onset conditions and carrier traits. Participants (n = 15) who received P/LP results were invited to participate in an interview at least 3 months after receiving their results. RESULTS:Eleven individuals (ages 14-19 years) participated in an interview. Most interviewees accurately recalled their P/LP results and reported satisfaction with learning personal genetic information, despite experiencing short-lived anxiety and confusion. While participants had knowledge of relevant risk reduction and screening measures, most viewed their genetic test results as a future consideration. Several participants' family members underwent cascade testing after learning the young person's results. Reactions to or risk-reducing behaviors taken since learning results did not differ between disease categories associated with the result. CONCLUSION:In support of a growing body of empirical research engaging young people in genetic testing decisions and outcomes, our findings suggest that young people who choose to learn genetic information about themselves understand the implications and potential actionability of P/LP results and actively incorporate results into their and their family members' lives.
INTRODUCTION:Fabry disease (FD) is a multi-systemic, X-linked lysosomal storage disorder caused by decreased α-galactosidase activity. Early diagnosis enables timely treatment, but enzyme-based newborn screening (NBS) may not detect affected females. We hypothesized that enzyme-based NBS limitations contribute to sex-based diagnostic disparities in FD and investigated these differences. METHODS:Retrospective cohort analyses used data from the Fabry Registry (FR: 2001-2023) and Tennessee NBS (2017-2024). Sex differences in diagnosis via NBS, biochemical phenotype, symptom onset, and treatment initiation were analyzed using Wilcoxon and chi-square tests. RESULTS:Among 8,657 FR individuals, 73 (67 males, 6 females) were identified via NBS. FR data show that affected females had significantly higher residual α-galactosidase activity than affected males (leukocyte median: 45.9% vs. 3.9%, plasma median: 32.5% vs. 3.9%; p < 0.0001 for both). FR females had delayed symptom onset (18.1 vs. 11.1 years), later diagnosis (35.5 vs. 30.8 years), and lower treatment rates (51.1% vs. 80.8%) compared to males (all %, p < 0.0001). Tennessee NBS detected 25 males but no females. CONCLUSION:Females with FD have delays in symptom onset, diagnosis, and treatment compared to males. Furthermore, higher residual enzyme activity causes current enzyme-based NBS to miss most females. Incorporating sex-specific cutoffs and/or molecular sequencing into NBS could improve early detection and reduce sex-based disparities.
Introduction: Genomic medicine enables early detection of treatable conditions and supports personalized care across all populations; however, evidence guiding its implementation in resource-constrained healthcare settings remains limited. Methods: Using a mixed-methods approach, this study evaluated the readiness of an Alabama Federally Qualified Health Center (FQHC) to implement genomic medicine as part of routine clinical care. Staff members (e.g., physicians, nurses, medical assistants, and administrators) completed surveys, individual interviews, a concept mapping session, and a nominal group technique exercise. Results: Study participants included 13 clinic members. Interviews and mapping revealed three dominant barriers: staffing shortages, financial constraints, and language obstacles. Facilitators included a strong commitment to quality care, alignment with the clinical mission, and supportive leadership. Survey results (N = 12) revealed mean scores in the positive range for culture, learning climate, and leadership engagement, whereas scores for stress, available resources, and readiness for change were nearer to the neutral midpoint, suggesting potential practical constraints on genomic implementation. The use of the CFIR-ERIC Implementation Strategy Matching Tool allowed the team and participants to evaluate nine candidate strategies, prioritizing those with high feasibility and impact. The evaluation was visually developed into an impact matrix which placed patient and family involvement, tailored educational materials, educational meetings, and designated genomic medicine leadership in the high-feasibility/high-impact quadrant. These strategies directly address identified barriers and fit existing clinical strengths, which is important for equitable precision-medicine adoption. Conclusion: Findings indicate that FQHCs can advance genomic services through culturally attuned patient engagement, structured provider training, and clear leadership roles.
INTRODUCTION:Cancer imposes a substantial burden characterized by high morbidity and mortality, reduced quality of life, and increased healthcare costs. This burden is expected to rise due to aging populations and persistent exposure to risk factors. Although emerging cancer technologies hold promise for improving clinical and economic outcomes across the care continuum, translating research findings into routine clinical practice remains a major bottleneck. The European Commission has prioritized addressing this challenge by fostering the rapid adoption of safer and more effective interventions. As part of its strategic plan, the European Union (EU) has launched research and innovation initiatives aimed at integrating cancer genomic technologies into public health and clinical systems. The CAN.HEAL evaluation framework presents a structured approach to classifying innovative cancer-related interventions by maturity level and to guide researchers and decision-makers in supporting adoption and scale-up efforts. METHODS:The evaluation framework was developed within the CAN.HEAL consortium, under the EU strategic cancer initiative that funded this research and innovation action, and agreed upon a consensus-based, iterative methodology including the stakeholders' perspectives. Key steps included landscape analysis, identification of key actions, structured discussions, expert consultations, and pilot testing of the assessment tool. The selected dimensions - grounded in equity, early health technology assessment, and innovation adoption principles - were hierarchically organized into subdomains, domains, and three overarching dimensions. A two-step scoring system was used to assess each key action across planning/definition and execution stages, with weighted final scores. The CAN.HEAL evaluation framework defines three adoption readiness levels, ranging from implementation at the healthcare provider level to integration across multiple healthcare systems. A structured 71-key action assessment tool, organized into three dimensions, was used to determine each intervention level: (1) equity - capacity building, research equity, and access; (2) impact assessment - early clinical development, cost considerations, and broader value; and (3) implementation, adoption, and scale-up readiness - desirability, feasibility, and viability from developer and adopter perspectives, including reimbursement pathways. CONCLUSION:The CAN.HEAL evaluation framework is designed to offer a systematic, evidence-informed approach to assessing the adoption readiness of cancer-related innovations. Further validation in cross-border, real-world settings is needed to ensure practical utility and scalability.
INTRODUCTION:Global studies have shown a bidirectional association of gestational diabetes mellitus (GDM) with postpartum depression (PPD). Despite high GDM prevalence in Pakistan (3.3%-17.8%), no prior studies have explored its link with PPD. In this study, association between GDM and risk of developing PPD was investigated and risk factors for PPD were identified using the gold-standard Edinburgh Postnatal Depression Scale (EPDS). Evidence suggests that PPD has strong genetic basis. The BDNF gene is a known candidate for PPD pathogenesis, while the orexin system is linked to arousal, energy metabolism, with emerging role in neuropsychiatric disorders. This study is the first study to explore association of orexin SNP ORX1 10914456 with PPD together with the BDNF SNP rs6265 (Val/Met66), among participants with and without GDM diagnosis. METHODS:Among 1,000 women approached in hospitals of Islamabad, Rawalpindi, 800 met inclusion criteria (400 GDM, 400 non-GDM controls) and were genotyped for BDNF and orexin SNPs. Participants completed the EPDS 1 week postpartum. RESULTS:Using a cutoff of ≥13, 84.9% of GDM patients and 18% of non-GDM controls scored ≥13 on EPDS (χ2 = 78.337, p < 0.00001). Multivariate logistic regression revealed GDM diagnosis, BMI >25, fasting plasma glucose >126 mg/dL, 31-39-week gestation, <12 years of education, and urban locality as significant risk factors for PPD. GDM diagnosis increased odds of PPD by 2.5-fold (OR = 2.5, 95% CI: 21.48-4.31, p < 0.0001). The orexin SNP Orx1 10914456, CC genotype and BDNF SNP rs6265, AA genotype increased the odds of having higher EPDS scores in GDM patients by 3.11 (OR = 3.11, 95% CI: 1.29-7.47, p < 0.001) and 3.3 (OR = 3.3, 95% CI: 1.31-8.13, p = 0.04, p < 0.05), respectively, in comparison to other genotypic variants. CONCLUSION:Our study supports orexin and BDNF system-targeted therapies for PPD.
INTRODUCTION:Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A (aGAL) deficiency. Newborn screening (NBS) programs for FD have been implemented in several US states; however, its effectiveness in identifying affected females remains uncertain. We hypothesized that sex-specific inequality of NBS-based detection of FD results in different diagnostic pathways for males and females with FD. METHODS:We compared diagnostic approaches for males and females with FD using Tennessee NBS results and Vanderbilt Lysosomal Storage Disorders Database (VLSDD). Sex-specific detection differences were assessed using Fisher's exact test (α = 0.05). RESULTS:Tennessee NBS identified 25 males but no females with FD from 2017 to 2024. In VLSDD, among 81 individuals with FD, sex distribution was nearly equal (42 males, 39 females). Among males, 26/42 (62%) were diagnosed via NBS, 7/42 (17%) through known family history, and 9/42 (21%) based on clinical symptoms. All 16 males diagnosed through non-NBS were born before its implementation. In contrast, none of the 39 females were diagnosed through NBS (p value <0.05). Of these, 13/39 (33%) were diagnosed through cascade testing following their sons' detection by NBS, with a median age at diagnosis of 28 years (25th-75th percentile: 24.5-34.0). Of the remaining 26 females, 12/26 (46%) were diagnosed after a family member was diagnosed through clinical symptoms and 14/26 (54%) were diagnosed through clinical symptoms. CONCLUSIONS:NBS effectively identifies affected males but fails to detect females with FD, though it can indirectly facilitate diagnosis of older female relatives.
Introduction: This paper describes methods for a national study evaluating the implementation of the National Collegiate Athletic Association's (NCAA) policy on sickle cell trait (SCT) screening of athletes and describes attitudes toward the screening. Methods: In Fall 2020, 343 Division I schools, 302 Division II schools, and 426 Division III schools were invited to participate in this national survey. Results: Across 123 participating schools, a total of 168 sport medicine administrators (121 head athletic trainers and 47 team physicians), 268 athletic staff (128 staff athletic trainers and 140 coaches), and 1,424 athletes from basketball, football, soccer, lacrosse, track and field completed the survey. While the vast majority of respondents agreed/strongly agreed with the screening policy, there was varying support for how the policy was implemented including prioritizing SCT screening versus screening for other conditions (40-50% agreed/strongly agreed), focusing on sports with higher risk of overexertion versus universal screening (50-75% agreed/strongly agreed), and focusing on racial and ethnic groups where SCT is more prevalent (25-40% agreed/strongly agreed). Perspectives varied by NCAA division and race. Higher SCT knowledge scores were associated with believing that screening all athletes for SCT is important. Conclusions: Discussion of these findings provides important context for assessing how genetic screening requirements are implemented within collegiate athletics and more broadly.
Introduction: Family cancer history (FCH) provides insight into cancer risk and can guide prevention efforts. Black Americans experience high cancer burden and report several barriers to FCH knowledge due to family communication challenges. Few studies have examined family-level factors that impact FCH communication in Black Americans. This study employed a qualitative design to examine the family communication environments of those who communicated more (i.e., disseminators) versus less or no change (i.e., non-disseminators) about FCH, within the last year. Methods: This is a secondary data analysis of a larger study that implemented a community education program on how to calculate cancer risk from family history (i.e., Families SHARE). Black Americans (N = 39) participated in community education workshops (N = 12) and discussed family communication environments. A codebook was developed a priori and revised iteratively using a consensus approach. Dedoose qualitative software supported establishing inter-rater reliability (Cohen's kappa = 0.83) and thematic analysis. Participants received USD 50 for workshop completion. Results: Pre-workshop disseminators (n = 14) and non-disseminators (n = 25) averaged 59 years of age, were 50% female, and earned
INTRODUCTION:A 2016 study showed that limited health literacy was associated with lower awareness of family health history. However, this analysis was conducted among adult patients in St. Louis, Missouri, thereby warranting broader replication. METHODS:We quantified the association between health literacy and awareness of family health history using a nationwide cross-sectional study of 286,293 All of Us Research Program participants. Modified Poisson regression models estimated PRs (PRs): model 1 (unadjusted), model 2 (demographic factors), model 3 (socioeconomic status), model 4 (health insurance), model 5 (self-rated health status), and model 6 (number of chronic health conditions). RESULTS:The average age was 53 years (SD = 17), with 4% who self-reported no awareness of family health history and 17% who had limited health literacy. Without controlling for confounders (model 1), participants with limited health literacy were 3.06 (95% confidence interval [CI]: 2.95-3.17) times more likely than those with adequate health literacy to report no awareness of family health history. This significant association persisted but attenuated in models 2 (adjusted PR [aPR]: 2.04, 95% CI: 1.96-2.12) and 3 (aPR: 1.43, 95% CI: 1.37-1.49). The association remained stable in models 4-6 with the sequential addition of health insurance coverage (aPR: 1.42, 95% CI: 1.37-1.48), self-rated health status (aPR: 1.42, 95% CI: 1.36-1.47), and number of chronic health conditions (aPR: 1.42, 95% CI: 1.36-1.48). CONCLUSION:These findings indicate that increasing health literacy may increase awareness of family health history, which is vital for delivery of personalized healthcare and active patient participation in precision medicine.
