Genetic ancestry and diagnostic yield of exome sequencing in a diverse population.

It has been suggested that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental/subcontinental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Cases (N = 845) with suspected genetic disorders underwent ES for diagnosis. Continental/subcontinental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov-Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. We observed no reduction in overall DY associated with any genetic ancestry (African, Native American, East Asian, European, Middle Eastern, South Asian). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.

Patient Perspectives on Social Risk Screening and Documentation in a Dermatology Clinic.

Importance: Providing person-centered dermatologic care includes consideration of social risk factors, such as housing instability and unreliable transportation, that may affect clinical management. Patients' perspectives on social risk screening and documentation in dermatology clinics have not yet been evaluated. Objective: To understand patients' perspectives on social risk screening and documentation in a dermatology clinic. Design, Setting, and Participants: This mixed-methods study used a survey and semistructured interviews and was conducted in a general dermatology clinic at a large urban public hospital. Patients at the clinic were eligible to complete the survey if they were 18 years or older; able to speak and read English, Spanish, or Cantonese; and comfortable using a computer tablet. Survey participants who preferred to use English were eligible for interviews. The survey included social risk screening questions, measures of acceptability, and questions on social risk factors associated with patient acceptability. Semistructured interviews were conducted to explore attitudes and beliefs about social risk screening and documentation. Survey and interview findings were integrated during data analysis through development of themes and joint display. Data were analyzed from December 2021 to April 2023. Main Outcomes and Measures: There were 2 outcome measures of acceptability: appropriateness of screening in a dermatology clinic and comfort with documentation of social risk in the electronic health record (EHR). Results: A total of 135 participants (including 73 males [54.1%]) answered both measures of acceptability in the survey. Of these participants, 116 (85.9%) reported that social risk screening in their dermatology clinic was very or somewhat appropriate and 85 (63.0%) reported being completely or somewhat comfortable with having their social risks documented in the EHR. Themes that were developed from surveys and interviews were the (1) role of interpersonal factors in willingness to disclose social risks, (2) implications of institutional trust for willingness to disclose and comfort with documentation, and (3) relevance of screening in a dermatology clinic. Conclusions and Relevance: Results of this study showed that most participants found social risk screening to be appropriate in a dermatology clinic, although a smaller proportion of participants were comfortable with EHR documentation of their social risks. Optimizing patients' trust in their physicians and the medical system, while addressing privacy and discrimination concerns, may help facilitate disclosure of social risks.

Access to prenatal exome sequencing for fetal malformations: A qualitative landscape analysis in the US.

OBJECTIVE: There is increasing evidence supporting the clinical utility of next generation sequencing for identifying fetal genetic disorders. However, there are limited data on the demand for and accessibility of these tests, as well as payer coverage in the prenatal context. We sought to identify clinician perspectives on the utility of prenatal exome sequencing (ES) and on equitable access to genomic technologies for the care of pregnancies complicated by fetal structural anomalies. METHOD: We conducted two focus group discussions and six interviews with a total of 13 clinicians (11 genetic counselors; 2 Maternal Fetal Medicine/Geneticists) from U.S. academic centers and community clinics. RESULTS: Participants strongly supported ES for prenatal diagnostic testing in pregnancies with fetal structural anomalies. Participants emphasized the value of prenatal ES as an opportunity for a continuum of care before, during, and after a pregnancy, not solely as informing decisions about abortions. Cost and coverage of the test was the main access barrier, and research was the main pathway to access ES in academic centers. CONCLUSION: Further integrating the perspectives of additional key stakeholders are important for understanding clinical utility, developing policies and practices to address access barriers, and assuring equitable provision of prenatal diagnostic testing.

Community Health Center Staff Perspectives on Financial Payments for Social Care.

Policy Points State and federal payers are actively considering strategies to increase the adoption of social risk screening and interventions in health care settings, including through the use of financial incentives. Activities related to social care in Oregon community health centers (CHCs) provided a unique opportunity to explore whether and how fee-for-service payments for social risk screening and navigation influence CHC activities. CHC staff, clinicians, and administrative leaders were often unaware of existing financial payments for social risk screening and navigation services. As currently designed, fee-for-service payments are unlikely to strongly influence CHC social care practices. CONTEXT: A growing crop of national policies has emerged to encourage health care delivery systems to ask about and try to address patients' social risks, e.g., food, housing, and transportation insecurity, in care delivery contexts. In this study, we explored how community health center (CHC) staff perceive the current and potential influence of fee-for-service payments on clinical teams' engagement in these activities. METHODS: We interviewed 42 clinicians, frontline staff, and administrative leaders from 12 Oregon CHC clinical sites about their social care initiatives, including about the role of existing or anticipated financial payments intended to promote social risk screening and referrals to social services. Data were analyzed using both inductive and deductive thematic analysis approaches. FINDINGS: We grouped findings into three categories: participants' awareness of existing or anticipated financial incentives, uses for incentive dollars, and perceived impact of financial incentives on social care activities in clinical practices. Lack of awareness of existing incentives meant these incentives were not perceived to influence the behaviors of staff responsible for conducting screening and providing referrals. Current or anticipated meaningful uses for incentive dollars included paying for social care staff, providing social services, and supporting additional fundraising efforts. Frontline staff reported that the strongest motivator for clinic social care practices was the ability to provide responsive social services. Clinic leaders/managers noted that for financial incentives to substantively change CHC practices would require payments sizable enough to expand the social care workforce as well. CONCLUSIONS: Small fee-for-service payments to CHCs for social risk screening and navigation services are unlikely to markedly influence CHC social care practices. Refining the design of financial incentives-e.g., by increasing clinical teams' awareness of incentives, linking screening to well-funded social services, and changing incentive amounts to support social care staffing needs-may increase the uptake of social care practices in CHCs.

The Need to Standardize the Reanalysis of Genomic Sequencing Results: Findings from Interviews with Underserved Families in Genomic Research.

The reanalysis of genomic sequencing results has the potential to provide results that are of considerable medical and personal importance to recipients. Employing interviews with forty-seven predominantly medically underserved families and ethnographic observations we argue that there is pressing need to standardize the approach taken to reanalysis. Our findings highlight that study participants were unclear as to the likelihood of reanalysis happening, the process of initiating reanalysis, and whether they would receive revised results. Their reflections mirror the lack a specific focus upon reanalysis within consent and results sessions as observed in clinical settings. Mechanisms need to be put into place that standardize the approach to reanalysis in research and in clinical contexts. This would enable clinicians and genetic counsellors to communicate clearly with research participants with respect to potential for reanalysis of results and the process of reanalysis. We argue that that the role of reanalysis is too important to be referred to in an ad-hoc manner. Furthermore, the ad-hoc nature of the current process may increase health inequities given the likelihood that only those families who have the means to press for reanalysis are likely to receive it.

Clinical decision support and electronic interventions to improve care quality in chronic liver diseases and cirrhosis.

Significant quality gaps exist in the management of chronic liver diseases and cirrhosis. Clinical decision support systems-information-driven tools based in and launched from the electronic health record-are attractive and potentially scalable prospective interventions that could help standardize clinical care in hepatology. Yet, clinical decision support systems have had a mixed record in clinical medicine due to issues with interoperability and compatibility with clinical workflows. In this review, we discuss the conceptual origins of clinical decision support systems, existing applications in liver diseases, issues and challenges with implementation, and emerging strategies to improve their integration in hepatology care.

Diagnostic Yield of Exome Sequencing in a Diverse Pediatric and Prenatal Population is not Associated with Genetic Ancestry.

Purpose: It has been hypothesized that diagnostic yield (DY) from Exome Sequencing (ES) may be lower among patients with non-European ancestries than those with European ancestry. We examined the association of DY with estimated continental genetic ancestry in a racially/ethnically diverse pediatric and prenatal clinical cohort. Methods: Cases (N=845) with suspected genetic disorders underwent ES for diagnosis. Continental genetic ancestry proportions were estimated from the ES data. We compared the distribution of genetic ancestries in positive, negative, and inconclusive cases by Kolmogorov Smirnov tests and linear associations of ancestry with DY by Cochran-Armitage trend tests. Results: We observed no reduction in overall DY associated with any continental genetic ancestry (Africa, America, East Asia, Europe, Middle East, South Asia). However, we observed a relative increase in proportion of autosomal recessive homozygous inheritance versus other inheritance patterns associated with Middle Eastern and South Asian ancestry, due to consanguinity. Conclusions: In this empirical study of ES for undiagnosed pediatric and prenatal genetic conditions, genetic ancestry was not associated with the likelihood of a positive diagnosis, supporting the ethical and equitable use of ES in diagnosis of previously undiagnosed but potentially Mendelian disorders across all ancestral populations.

"I Have Fought for so Many Things": Disadvantaged families' Efforts to Obtain Community-Based Services for Their Child after Genomic Sequencing.

BACKGROUND: Families whose child has unexplained intellectual or developmental differences often hope that a genetic diagnosis will lower barriers to community-based therapeutic and support services. However, there is little known about efforts to mobilize genetic information outside the clinic or how socioeconomic disadvantage shapes and constrains outcomes. METHODS: We conducted an ethnographic study with predominantly socioeconomically disadvantaged families enrolled in a multi-year genomics research study, including clinic observations and in-depth interviews in English and Spanish at multiple time points. Coding and thematic development were used to collaboratively interpret fieldnotes and transcripts. RESULTS: Thirty-two families participated. Themes included familial expectations that a genetic diagnosis could be translated into information, understanding, and assistance to improve the quality of a child's day-to-day life. After sequencing, however, genetic information was not readily converted into improved access to services beyond the clinic, with families often struggling to use a genetic diagnosis to advocate for their child. CONCLUSION: Families' ability to use a genetic diagnosis as an effective advocacy tool beyond the clinic was limited by the knowledge and resources available to them, and by the eligibility criteria used by therapeutic service providers' - which focused on clinical diagnosis and functional criteria more than etiologic information. All families undertaking genomic testing, particularly those who are disadvantaged, need additional support to understand the limits and potential benefits of genetic information beyond the clinic.

Diagnostic yield of pediatric and prenatal exome sequencing in a diverse population.

The diagnostic yield of exome sequencing (ES) has primarily been evaluated in individuals of European ancestry, with less focus on underrepresented minority (URM) and underserved (US) patients. We evaluated the diagnostic yield of ES in a cohort of predominantly US and URM pediatric and prenatal patients suspected to have a genetic disorder. Eligible pediatric patients had multiple congenital anomalies and/or neurocognitive disabilities and prenatal patients had one or more structural anomalies, disorders of fetal growth, or fetal effusions. URM and US patients were prioritized for enrollment and underwent ES at a single academic center. We identified definitive positive or probable positive results in 201/845 (23.8%) patients, with a significantly higher diagnostic rate in pediatric (26.7%) compared to prenatal patients (19.0%) (P = 0.01). For both pediatric and prenatal patients, the diagnostic yield and frequency of inconclusive findings did not differ significantly between URM and non-URM patients or between patients with US status and those without US status. Our results demonstrate a similar diagnostic yield of ES between prenatal and pediatric URM/US patients and non-URM/US patients for positive and inconclusive results. These data support the use of ES to identify clinically relevant variants in patients from diverse populations.

Caregivers' and providers' perspectives of social and medical care after pediatric liver transplant: Results from the multicenter SOCIAL-Tx study.

Disparities exist in pediatric liver transplant (LT). We characterized barriers and facilitators to providing transplant and social care within pediatric LT clinics. This was a multicenter qualitative study. We oversampled caregivers reporting household financial strain, material economic hardship, or demonstrating poor health literacy. We also enrolled transplant team members. We conducted semistructured interviews with participants. Caregiver interviews focused on challenges addressing transplant and household needs. Transplant provider interviews focused on barriers and facilitators to providing social care within transplant teams. Interviews were recorded, transcribed, and coded according to the Capability, Opportunity, Motivation-Behavior model. We interviewed 27 caregivers and 27 transplant team members. Fifty-two percent of caregivers reported a household income <$60,000, and 62% reported financial resource strain. Caregivers reported experiencing (1) high financial burdens after LT, (2) added caregiving labor that compounds the financial burden, (3) dependency on their social network's generosity for financial and logistical support, and (4) additional support being limited to the perioperative period. Transplant providers reported (1) relying on the pretransplant psychosocial assessment for identifying social risks, (2) discomfort initiating social risk discussions in the post-transplant period, (3) reliance on social workers to address new social risks, and (4) social workers feeling overburdened by quantity and quality of the social work referrals. We identified barriers to providing effective social care in pediatric LT, primarily a lack of comfort in assessing and addressing new social risks in the post-transplant period. Addressing these barriers should enhance social care delivery and improve outcomes for these children.

Pediatric Primary Care Perspectives of Mental Health Services Delivery during the COVID-19 Pandemic.

Due to a national shortage of child and adolescent psychiatrists, pediatric primary care providers (PCPs) are often responsible for the screening, evaluation, and treatment of mental health disorders. COVID-19 pandemic stay-at-home orders decreased access to mental health care and increased behavioral and emotional difficulties in children and adolescents. Despite increased demand upon clinicians, little is known about mental health care delivery in the pediatric primary care setting during the pandemic. This focus group study explored the experiences of pediatric PCPs and clinical staff delivering mental health care during the pandemic. Transcripts from nine focus groups with San Francisco Bay Area primary care practices between April and August 2020 were analyzed using a thematic analysis approach. Providers expressed challenges at the patient-, provider-, and system-levels. Many providers reported increased patient mental health symptomatology during the pandemic, which was often intertwined with patients' social determinants of health. Clinicians discussed the burden of the pandemic their own wellness, and how the rapid shift to telehealth primary care and mental health services seemed to hinder the availability and effectiveness of many resources. The findings from this study can inform the creation of new supports for PCPs and clinical staff providing mental health care.

Parental Hopes and Understandings of the Value of Prenatal Diagnostic Genomic Sequencing: A Qualitative Analysis.

Objective: To provide qualitative empirical data on parental expectations of diagnostic prenatal genomic sequencing and the value of the results to families. Methods: We interviewed 15 families-mothers and/or fathers-who had had prenatal genomic sequencing about their expectations and their respective evaluations of the benefits of genomic sequencing. Results: Families' hopes for genetic sequencing clustered around three themes: hoping to identify the cause of the fetal anomaly in a terminated pregnancy; hopes for guidance as to the likely outcome of current pregnancy; and hopes for information to support future family planning. In addition, hopes were discussed in terms of the potential for results to be beneficial in acquiring greater knowledge, while at the same time recognizing that new knowledge may raise more questions. Assessment of the value of sequencing largely mirrored these expectations when positive results seen. Negative results can also be seen as valuable in ruling out a genetic cause and in providing certainty that families had done everything that they could to know about the cause of fetal demise. Conclusion: It would appear that with guidance from genetic counsellors, families were largely able to navigate the many uncertainties of prenatal genomic sequencing and thus see themselves as benefitting from sequencing. However, support structures are essential to guide them through their expectations and interpretations of results to minimize possible harms. Engaging in the process of genomic sequencing was seen as beneficial in of itself to families who would otherwise be left without any options to seek diagnostic answers.

"Let's Just Wait Until She's Born": Temporal Factors That Shape Decision-Making for Prenatal Genomic Sequencing Amongst Families Underrepresented in Genomic Research.

Genomic sequencing has been increasingly utilized for prenatal diagnosis in recent years and this trend is likely to continue. However, decision-making for parents in the prenatal period is particularly fraught, and prenatal sequencing would significantly expand the complexity of managing health risk information, reproductive options, and healthcare access. This qualitative study investigates decision-making processes amongst parents who enrolled or declined to enroll in the prenatal arm of the California-based Program in Prenatal and Pediatric Genome Sequencing (P3EGS), a study in the Clinical Sequencing Evidence-Generating Research (CSER) consortium that offered whole exome sequencing for fetal anomalies with a focus on underrepresented groups in genomic research. Drawing on the views of 18 prenatal families who agreed to be interviewed after enrolling (n = 15) or declining to enroll (n = 3) in P3EGS, we observed that the timing of sequencing, coupled with unique considerations around experiences of time during pregnancy and prenatal testing, intersect with structural supports beyond the clinic to produce preferences for and against prenatal sequencing and to contain the threat of unwelcome, uncertain knowledge. Particularly for those without structural supports, finding out consequential information may be more palatable after the birth, when the first stage of the uncertain future has been revealed. Future research should examine the role of temporality in decision-making around prenatal genomic sequencing across diverse population cohorts, in order to observe more precisely the role that structural barriers play in patient preferences.

Perspectives and preferences regarding genomic secondary findings in underrepresented prenatal and pediatric populations: A mixed-methods approach.

PURPOSE: Patients undergoing clinical exome sequencing (ES) are routinely offered the option to receive secondary findings (SF). However, little is known about the views of individuals from underrepresented minority pediatric or prenatal populations regarding SF. METHODS: We explored the preferences for receiving hypothetical categories of SF (H-SF) and reasons for accepting or declining actual SF through surveying (n = 149) and/or interviewing (n = 47) 190 families undergoing pediatric or prenatal ES. RESULTS: Underrepresented minorities made up 75% of the probands. In total, 150 families (79%) accepted SF as part of their child/fetus's ES. Most families (63%) wanted all categories of H-SF. Those who declined SF as part of ES were less likely to want H-SF across all categories. Interview findings indicate that some families did not recall their SF decision. Preparing for the future was a major motivator for accepting SF, and concerns about privacy, discrimination, and psychological effect drove decliners. CONCLUSION: A notable subset of families (37%) did not want at least 1 category of H-SF, suggesting more hesitancy about receiving all available results than previously reported. The lack of recollection of SF decisions suggests a need for alternative communication approaches. Results highlight the importance of the inclusion of diverse populations in genomic research.

Differences in Hospitals' Workplace Violence Incident Reporting Practices: A Mixed Methods Study.

Workplace violence (WV) is a significant and growing problem for health care workers. Increased recognition of the need for improved protections has led to policy initiatives at the state and federal levels, including national Joint Commission requirements that went into effect January 2022. California's WV prevention legislation was phased in during 2017-2018 and requires hospitals to use a new incident reporting system, the Workplace Violent Incident Reporting System (WVIRS) for Hospitals. We analyzed WVIRS data collected during the first three years of its implementation, July 1, 2017 - June 30, 2020. In addition, we collected qualitative data from six California hospitals/hospital systems during 2019-2020 to better understand reporting practices. Over the three-year period, the 413 hospitals using the WVIRS reported between zero and six incidents per staffed bed. Sixteen hospitals (3.9%) reported two or more incidents per staffed bed while the rest reported fewer than two incidents. Qualitative analysis identified that reporting procedures vary considerably among hospitals. Several organizations rely on workers to complete incident reports electronically while others assign managers or security personnel to data collection. Some hospitals appear to report only those incidents involving physical harm to the worker. Regulatory guidance for reporting practices and hospitals' commitment to thorough data collection may improve consistency. As hospitals throughout the U.S. consider practice changes to comply with new WV standards, those engaged in implementation efforts should look closely at reporting practices. Greater consistency in reporting across facilities can help to build evidence for best practices and lead to safety improvements.

Integration of stakeholder engagement from development to dissemination in genomic medicine research: Approaches and outcomes from the CSER Consortium.

PURPOSE: There is a critical need for genomic medicine research that reflects and benefits socioeconomically and ancestrally diverse populations. However, disparities in research populations persist, highlighting that traditional study designs and materials may be insufficient or inaccessible to all groups. New approaches can be gained through collaborations with patient/community stakeholders. Although some benefits of stakeholder engagement are recognized, routine incorporation into the design and implementation of genomics research has yet to be realized. METHODS: The National Institutes of Health-funded Clinical Sequencing Evidence-Generating Research (CSER) consortium required stakeholder engagement as a dedicated project component. Each CSER project planned and carried out stakeholder engagement activities with differing goals and expected outcomes. Examples were curated from each project to highlight engagement strategies and outcomes throughout the research lifecycle from development through dissemination. RESULTS: Projects tailored strategies to individual study needs, logistical constraints, and other challenges. Lessons learned include starting early with engagement efforts across project stakeholder groups and planned flexibility to enable adaptations throughout the project lifecycle. CONCLUSION: Each CSER project used more than 1 approach to engage with relevant stakeholders, resulting in numerous adaptations and tremendous value added throughout the full research lifecycle. Incorporation of community stakeholder insight improves the outcomes and relevance of genomic medicine research.

Readiness to implement on-site molecular testing for tuberculosis in community health centers in Uganda.

BACKGROUND: Newer molecular testing platforms are now available for deployment at lower-level community health centers. There are limited data on facility- and health worker-level factors that would promote successful adoption of such platforms for rapid tuberculosis (TB) testing and treatment initiation. Our study aimed to assess readiness to implement onsite molecular testing at community health centers in Uganda, a high TB burden country in sub-Saharan Africa. METHODS: To understand implementation readiness, we conducted a qualitative assessment guided by the Consolidated Framework for Implementation Research (CFIR) at 6 community health centers in central and eastern Uganda between February and April 2018. We conducted 23 in-depth, semi-structured interviews with health workers involved in TB care at each health center to assess TB-related work practices and readiness to adopt onsite molecular testing using the GeneXpert Edge platform. Interviews were transcribed verbatim and coded for thematic analysis. RESULTS: Participants (N=23) included 6 nurses/nursing assistants, 6 clinicians, 6 laboratory directors/technicians, 1 medical officer, 2 health center directors, and 2 other health workers involved in TB care. Health workers described general enthusiasm that on-site molecular testing could lead to greater efficiencies in TB diagnosis and treatment, including faster turn- around time for TB test results, lack of need for trained laboratory technicians to interpret results, and reduced need to transport sputum specimens to higher level facilities. However, health workers also expressed concerns about implementation feasibility. These included uncertainty about TB infection risk, safety risks from disposal of hazardous waste, a lack of local capacity to provide timely troubleshooting and maintenance services, and concerns about the security of GeneXpert devices and accessories. Health workers also expressed the need for backup batteries to support testing or charging when wall power is unstable. CONCLUSION: Our study generated a nuanced understanding of modifiable contextual barriers and led to direct revisions of implementation strategies for onsite molecular testing. The findings highlight that novel diagnostics should be implemented along with health system co-interventions that address contextual barriers to their effective uptake. Pre-implementation assessment of stakeholder perspectives, collaborative work processes, and institutional contexts is essential when introducing innovative technology in complex health care settings.

Perceived Utility of Genomic Sequencing: Qualitative Analysis and Synthesis of a Conceptual Model to Inform Patient-Centered Instrument Development.

BACKGROUND AND OBJECTIVES: Successful clinical integration of genomic sequencing (GS) requires evidence of its utility. While GS potentially has benefits (utilities) or harms (disutilities) across multiple domains of life for both patients and their families, there is as yet no empirically informed conceptual model of these effects. Our objective was to develop an empirically informed conceptual model of perceived utility of GS that captures utilities and disutilities for patients and their families across diverse backgrounds. METHODS: We took a patient-centered approach, in which we began with a review of existing literature followed by collection of primary interview data. We conducted semi-structured interviews to explore types of utility in a clinically and sociopolitically diverse sample of 60 adults from seven Clinical Sequencing Evidence-Generating Research (CSER) consortium projects. Interviewees had either personally received, or were parents of a child who had received, GS results. Qualitative data were analyzed using thematic analysis. Findings from interviews were integrated with existing literature on clinical and personal utility to form the basis of an initial conceptual model that was refined based on expert review and feedback. RESULTS: Five key utility types that have been previously identified in qualitative literature held up as primary domains of utility and disutility in our diverse sample. Interview data were used to specify and organize subdomains of an initial conceptual model. After expert refinement, the five primary domains included in the final model are clinical, emotional, behavioral, cognitive, and social, and several subdomains are specified within each. CONCLUSION: We present an empirically informed conceptual model of perceived utility of GS. This model can be used to guide development of instruments for patient-centered outcome measurement that capture the range of relevant utilities and disutilities and inform clinical implementation of GS.

The difficulties of broad data sharing in genomic medicine: Empirical evidence from diverse participants in prenatal and pediatric clinical genomics research.

PURPOSE: This study aimed to understand broad data sharing decisions among predominantly underserved families participating in genomic research. METHODS: Drawing on clinic observations, semistructured interviews, and survey data from prenatal and pediatric families enrolled in a genomic medicine study focused on historically underserved and underrepresented populations, this paper expands empirical evidence regarding genomic data sharing communication and decision-making. RESULTS: One-third of parents declined to share family data, and pediatric participants were significantly more likely to decline than prenatal participants. The pediatric population was significantly more socioeconomically disadvantaged and more likely to require interpreters. Opt-in was tied to altruism and participants' perception that data sharing was inherent to research participation. Opt-out was associated with privacy concerns and influenced by clinical staff's presentation of data handling procedures. The ability of participants to make informed choices during enrollment about data sharing was weakened by suboptimal circumstances, which was revealed by poor understanding of data sharing in follow-up interviews as well as discrepancies between expressed participant desires and official recorded choices. CONCLUSION: These empirical data suggest that the context within which informed consent process is conducted in clinical genomics may be inadequate for respecting participants' values and preferences and does not support informed decision-making processes.