Genetic Research within Indigenous Communities: Engagement Opportunities and Pathways Forward.

PURPOSE: Against a historical backdrop of researchers who violated trust through lack of benefit sharing, transparency, and engagement, efforts are underway to develop better approaches for genetic and genomic research with Indigenous communities. To increase engagement, there is a need to understand factors that impact researcher and community collaborations. This study aimed to understand the barriers, challenges, and facilitators of Indigenous Peoples in the US participating in genetic research. METHODS: We conducted 42 semi-structured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members across the US to explore perceived risks, benefits, barriers and facilitators of genetic research participation. RESULTS: Participants, identifying as Indigenous (88%) or non-Indigenous allies (12%), described their concerns, hesitancy, and fears about genetic research as well as the roles of trust, transparency, and respect for culture in facilitating partnerships. Previous harms - such as sample and data misuse, stigmatization, or misrepresentation by researchers - revealed strategies for building trust to create more equitable and reciprocal research partnerships. CONCLUSION: Participants in this study offered strategies for increasing genetic research engagement. The pathway forward should foster transparent research policies and practices to facilitate informed research that supports the needs and priorities of participants, communities, and researchers.

Exploring the role of digital tools in rare disease management: An interview-based study.

While digital tools, such as the Internet, smartphones, and social media, are an important part of modern society, little is known about the specific role they play in the healthcare management of individuals and caregivers affected by rare disease. Collectively, rare diseases directly affect up to 10% of the global population, suggesting that a significant number of individuals might benefit from the use of digital tools. The purpose of this qualitative interview-based study was to explore: (a) the ways in which digital tools help the rare disease community; (b) the healthcare gaps not addressed by current digital tools; and (c) recommended digital tool features. Individuals and caregivers affected by rare disease who were comfortable using a smartphone and at least 18 years old were eligible to participate. We recruited from rare disease organizations using purposive sampling in order to achieve a diverse and information rich sample. Interviews took place over Zoom and reflexive thematic analysis was utilized to conceptualize themes. Eight semistructured interviews took place with four individuals and four caregivers. Three themes were conceptualized which elucidated key aspects of how digital tools were utilized in disease management: (1) digital tools should lessen the burden of managing a rare disease condition; (2) digital tools should foster community building and promote trust; and (3) digital tools should provide trusted and personalized information to understand the condition and what the future may hold. These results suggest that digital tools play a central role in the lives of individuals with rare disease and their caregivers. Digital tools that centralize trustworthy information, and that bring the relevant community together to interact and promote trust are needed. Genetic counselors can consider these ideal attributes of digital tools when providing resources to individuals and caretakers of rare disease.

Advancing genomics to improve health equity.

Health equity is the state in which everyone has fair and just opportunities to attain their highest level of health. The field of human genomics has fallen short in increasing health equity, largely because the diversity of the human population has been inadequately reflected among participants of genomics research. This lack of diversity leads to disparities that can have scientific and clinical consequences. Achieving health equity related to genomics will require greater effort in addressing inequities within the field. As part of the commitment of the National Human Genome Research Institute (NHGRI) to advancing health equity, it convened experts in genomics and health equity research to make recommendations and performed a review of current literature to identify the landscape of gaps and opportunities at the interface between human genomics and health equity research. This Perspective describes these findings and examines health equity within the context of human genomics and genomic medicine.

Equity Concerns Across Pediatric Research Recruitment: An Analysis of Research Staff Interviews.

BACKGROUND AND OBJECTIVES: Difficulty recruiting individuals from minoritized and underserved populations for clinical research is well documented and has health equity implications. Previously, we reported findings from interviews with research staff about pediatric research recruitment processes. Respondents raised equity concerns related to recruitment and enrollment of participants from minoritized, low resourced, and underserved populations. We therefore decided to perform a secondary coding of the transcripts to examine equity-related issues systematically. METHODS: We conducted a process of secondary coding and analysis of interviews with research staff involved in recruitment for pediatric clinical research. Through consensus we identified codes relevant to equity and developed a conceptual framework including 5 stages of research. RESULTS: We analyzed 28 interviews and coded equity-related items. We report 6 implications of our findings. First, inequitable access to clinical care is an upstream barrier to research participation. Second, there is a need to increase research opportunities where underserved and under-represented populations receive care. Third, increasing research team diversity can build trust with patients and families, but teams must ensure adequate support of all research team members. Fourth, issues related to consent processes raise institutional-level opportunities for improvement. Fifth, there are numerous study procedure-related barriers to participation. Sixth, our analysis illustrates that individuals who speak languages other than English face barriers across multiple stages. CONCLUSIONS: Research staff members identified equity-related concerns and recommended potential solutions across 5 stages of the research process, which may guide those endeavoring to improve research recruitment for pediatric patients from minoritized and underserved populations.

Genetic research with Indigenous Peoples: perspectives on governance and oversight in the US.

Introduction: Indigenous Peoples are increasingly exerting governance and oversight over genomic research with citizens of their nations, raising questions about how best to enforce research regulation between American Indian, Alaska Native, and Native Hawaiian peoples and researchers. Methods: Using a community-engaged research approach, we conducted 42 semi-structured interviews with Tribal leaders, clinicians, researchers, policy makers, and Tribal research review board members about their perspectives on ethical issues related to genetics research with Indigenous Peoples in the US. Results: We report findings related to (1) considerations for Indigenous governance, (2) institutional relationships upholding sovereignty, (3) expectations for research approvals, and (4) agreements enacting Indigenous governance. Participants described concerns about different ways of exerting oversight, relationships and agreements between Indigenous Peoples and researchers, and gaps that need to be addressed to strengthen existing governance of genomic data. Discussion: The results will ultimately guide policy-making and development of new strategies for Indigenous Peoples to enforce oversight in research to promote ethically and culturally appropriate research.

Indigenous Peoples and research: self-determination in research governance.

Indigenous Peoples are reimagining their relationship with research and researchers through greater self-determination and involvement in research governance. The emerging discourse around Indigenous Data Sovereignty has provoked discussions about decolonizing data practices and highlighted the importance of Indigenous Data Governance to support Indigenous decision-making and control of data. Given that much data are generated from research, Indigenous research governance and Indigenous Data Governance overlap. In this paper, we broaden the concept of Indigenous Data Sovereignty by using the CARE Principles for Indigenous Data Governance to discuss how research legislation and policy adopted by Indigenous Peoples in the US set expectations around recognizing sovereign relationships, acknowledging rights and interests in data, and enabling Indigenous Peoples' participation in research governance.

An Ethical Framework for Research Using Genetic Ancestry.

A wide range of research uses patterns of genetic variation to infer genetic similarity between individuals, typically referred to as genetic ancestry. This research includes inference of human demographic history, understanding the genetic architecture of traits, and predicting disease risk. Researchers are not just structuring an intellectual inquiry when using genetic ancestry, they are also creating analytical frameworks with broader societal ramifications. This essay presents an ethics framework in the spirit of virtue ethics for these researchers: rather than focus on rule following, the framework is designed to build researchers' capacities to react to the ethical dimensions of their work. The authors identify one overarching principle of intellectual freedom and responsibility, noting that freedom in all its guises comes with responsibility, and they identify and define four principles that collectively uphold researchers' intellectual responsibility: truthfulness, justice and fairness, anti-racism, and public beneficence. Researchers should bring their practices into alignment with these principles, and to aid this, the authors name three common ways research practices infringe these principles, suggest a step-by-step process for aligning research choices with the principles, provide rules of thumb for achieving alignment, and give a worked case. The essay concludes by identifying support needed by researchers to act in accord with the proposed framework.

Wrestling with Social and Behavioral Genomics: Risks, Potential Benefits, and Ethical Responsibility.

In this consensus report by a diverse group of academics who conduct and/or are concerned about social and behavioral genomics (SBG) research, the authors recount the often-ugly history of scientific attempts to understand the genetic contributions to human behaviors and social outcomes. They then describe what the current science-including genomewide association studies and polygenic indexes-can and cannot tell us, as well as its risks and potential benefits. They conclude with a discussion of responsible behavior in the context of SBG research. SBG research that compares individuals within a group according to a "sensitive" phenotype requires extra attention to responsible conduct and to responsible communication about the research and its findings. SBG research (1) on sensitive phenotypes that (2) compares two or more groups defined by (a) race, (b) ethnicity, or (c) genetic ancestry (where genetic ancestry could easily be misunderstood as race or ethnicity) requires a compelling justification to be conducted, funded, or published. All authors agree that this justification at least requires a convincing argument that a study's design could yield scientifically valid results; some authors would additionally require the study to have a socially favorable risk-benefit profile.

Wrestling with Public Input on an Ethical Analysis of Scientific Research.

Bioethicists frequently call for empirical researchers to engage participants and community members in their research, but don't themselves typically engage community members in their normative research. In this article, we describe an effort to include members of the public in normative discussions about the risks, potential benefits, and ethical responsibilities of social and behavioral genomics (SBG) research. We reflect on what might-and might not- be gained from engaging the public in normative scholarship and on lessons learned about public perspectives on the risks and potential benefits of SBG research and the responsible conduct and communication of such research. We also provide procedural lessons for others in bioethics who are interested in engaging members of the public in their research.

Values and Practices to Strengthen Genetic Research Partnerships with Indigenous Communities.

Genetic datasets lack diversity and include very few data from Indigenous populations. Research models based on equitable partnership have the potential to increase Indigenous participation and have led to successful collaborations. We report here on a meeting of participants in four Indigenous community-university partnerships pursuing research on precision medicine. The goal of the meeting was to define values and practices that strengthen opportunities for genetic research. The group accorded the highest priority to developing trusting relationships, ensuring respect for Indigenous community authority, and pursuing research that has the potential to lead to community benefit. Supporting priorities included incorporation of Indigenous expertise in research planning, transparent communication, and development of community capacity, including capacity to participate in formulating research questions, informing research methodology, and leading research projects. Participants also noted the importance of attention to social determinants of health so that genetic contributors to health are evaluated in the appropriate context.

Extending the CARE Principles from tribal research policies to benefit sharing in genomic research.

Indigenous Peoples have historically been targets of extractive research that has led to little to no benefit. In genomics, such research not only exposes communities to harms and risks of misuse, but also deprives such communities of potential benefits. Tribes in the US have been exercising their sovereignty to limit this extractive practice by adopting laws and policies to govern research on their territories and with their citizens. Federally and state recognized tribes are in the strongest position to assert research oversight. Other tribes lack the same authority, given that federal and state governments do not recognize their rights to regulate research, resulting in varying levels of oversight by tribes. These governance measures establish collective protections absent from the US federal government's research oversight infrastructure, while setting expectations regarding benefits to tribes as political collectives. Using a legal epidemiology approach, the paper discusses findings from a review of Tribal research legislation, policy, and administrative materials from 26 tribes in the US. The discussion specifies issues viewed by tribes as facilitators and barriers to securing benefits from research for their nations and members/citizens, and describes preemptive and mitigating strategies pursued by tribes in response. These strategies are set within the framing of the CARE Principles for Indigenous Data Governance (Collective Benefit, Authority to Control, Responsibility, Ethics), a set of standards developed to ensure that decisions made about data pertaining to Indigenous communities at the individual and tribal levels are responsive to their values and collective interests. Our findings illustrate gaps to address for benefit sharing and a need to strengthen Responsibility and Ethics in tribal research governance.

A qualitative study of COVID-19 vaccine decision making among urban Native Americans.

Background: Significant disparities in COVID-19 morbidity and mortality exist for Native American (NA) people, the majority of whom live in urban areas. COVID-19 vaccination is a key strategy for mitigating these disparities; however, vaccination disparities affect NA communities. The current study investigated COVID-19 vaccine decision-making before widespread vaccine rollout occurred, among urban NA communities. We aimed to understand vaccine decision-making factors to develop recommendations about COVID-19 vaccine outreach. Methods: We conducted three in-depth virtual focus groups with 17 NA adults living in an urban community (Los Angeles County) between December 2020 and January 2021. Participants were recruited through NA community-based organizations and community stakeholders. Reflexive thematic analysis was conducted using Atlas.ti. Findings: Participants in this study identified two overarching themes with implications for health vaccination campaigns. First, participants described a need for tailored information and outreach, including NA vaccine outreach that addresses misconceptions about vaccine development to calm fears of experimentation and support communication of vaccine evidence specific to NA people. Second, participants suggested strategies to improve public health resources in the urban NA community, such as the need for unified, proactive communication across trusted NA entities, navigation support to improve vaccine accessibility, and adequately resourcing health partnerships with and among trusted NA community agencies for improved reach. Conclusion: In this qualitative study, we found that urban NA participants reported several factors that affected their vaccine decision-making, including a lack of tailored information for their communities. Our findings also underscore the need to work with tribes, tribal leadership, and urban NA serving organizations to coordinate vaccine communication and distribution to urban communities where the majority of NAs now reside. Further, these findings have implications for COVID-19 vaccine outreach among urban NA communities and demonstrate the need for clear and tailored engagement about the COVID-19 vaccine.

Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research.

Communicating Precision Medicine Research: Multidisciplinary Teams and Diverse Communities.

INTRODUCTION: Precision medicine research investigates the differences in individuals' genetics, environment, and lifestyle to tailor health prevention and treatment options as part of an emerging model of health care delivery. Advancing precision medicine research will require effective communication across a wide range of scientific and health care disciplines and with research participants who represent diverse segments of the population. METHODS: A multidisciplinary group convened over the course of a year and developed precision medicine research case examples to facilitate precision medicine research discussions with communities. RESULTS: A shared definition of precision medicine research as well as six case examples of precision medicine research involving genetic risk, pharmacogenetics, epigenetics, the microbiome, mobile health, and electronic health records were developed. DISCUSSION/CONCLUSION: The precision medicine research definition and case examples can be used as planning tools to establish a shared understanding of the scope of precision medicine research across multidisciplinary teams and with the diverse communities in which precision medicine research will take place. This shared understanding is vital for successful and equitable progress in precision medicine.

Is there a way to reduce the inequity in variant interpretation on the basis of ancestry?

The underrepresentation of non-European ancestry groups in current genomic databases complicates interpretation of their genetic test results, yielding a much higher prevalence of variants of uncertain significance (VUSs). Such VUS findings can frustrate the goals of genetic testing, create anxiety in patients, and lead to unnecessary medical interventions. Approaches to addressing underrepresentation of people with genetic ancestries other than European are being undertaken by broad-based recruitment efforts. However, some underrepresented groups have concerns that might preclude participation in such efforts. We describe here two initiatives aimed at meeting the needs of underrepresented ancestry groups in genomic datasets. The two communities, the Sephardi Jewish community in New York and First Peoples of Canada, have very different concerns about contributing to genomic research and datasets. Sephardi concerns focus on the possible negative effects of genetic findings on the marriage prospects of family members. Canadian Indigenous populations seek control over the research uses to which their genetic data would be put. Both cases involve targeted efforts to respond to the groups' concerns; these efforts include governance models aimed at ensuring that the data are used primarily to inform clinical test analyses and at achieving successful engagement and participation of community members. We suggest that these initiatives could provide models for other ancestral groups seeking to improve the accuracy and utility of clinical genetic testing while respecting the underlying preferences and values of community members with regard to the use of their genetic data.

"The System Doesn't Let Us in"-A Call for Inclusive COVID-19 Vaccine Outreach Rooted in Los Angeles Latinos' Experience of Pandemic Hardships and Inequities.

OBJECTIVE: Latino adults in Los Angeles have experienced disproportionate cases, deaths, and socioeconomic impacts from the COVID-19 pandemic. This qualitative study aimed to explore community perspectives on readiness for COVID-19 vaccination and to identify culturally tailored vaccine outreach strategies. METHODS: We conducted virtual focus groups with Los Angeles County Latino/a residents via Zoom between December 2020 to January 2021, as the first COVID-19 vaccines were receiving Emergency Use Authorization (EUA). Focus groups were facilitated in Spanish and English by bilingual members of the research team. Discussions were analyzed via Atlas.ti software using reflexive thematic analysis. RESULTS: Three focus groups (n = 15; four to six people each; two Spanish focus groups; one English) were conducted. Thematic findings centered on Latino COVID-19 vaccine equity: (1) Disproportionate infection risk due to essential worker status and socioeconomic burdens, misinformation, and familial or cultural tensions (2) Concerns for inequitable vaccine access due to immigration fears and limited healthcare access, and (3) A need for community-centered COVID-19 vaccine outreach and access. CONCLUSIONS: Our study on early Latino adult reactions to vaccine roll-out suggests the need for outreach strategies centering on validating community hardships, combating dis-/misinformation through trusted sources, and addressing socio-economic needs impacted by the pandemic.

Ethical Guidance in Human Paleogenomics: New and Ongoing Perspectives.

Over the past two decades, the study of ancient genomes from Ancestral humans, or human paleogenomic research, has expanded rapidly in both scale and scope. Ethical discourse has subsequently emerged to address issues of social responsibility and scientific robusticity in conducting research. Here, we highlight and contextualize the primary sources of professional ethical guidance aimed at paleogenomic researchers. We describe the tension among existing guidelines, while addressing core issues such as consent, destructive research methods, and data access and management. Currently, there is a dissonance between guidelines that focus on scientific outcomes and those that hold scientists accountable to stakeholder communities,such as descendants. Thus, we provide additional tools to navigate the complexities of ancient DNA research while centering engagement with stakeholder communities in the scientific process.

The Human Pangenome Project: a global resource to map genomic diversity.

The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene-disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.

Using Indigenous Standards to Implement the CARE Principles: Setting Expectations through Tribal Research Codes.

Biomedical data are now organized in large-scale databases allowing researchers worldwide to access and utilize the data for new projects. As new technologies generate even larger amounts of data, data governance and data management are becoming pressing challenges. The FAIR principles (Findable, Accessible, Interoperable, and Reusable) were developed to facilitate data sharing. However, the Indigenous Data Sovereignty movement advocates for greater Indigenous control and oversight in order to share data on Indigenous Peoples' terms. This is especially true in the context of genetic research where Indigenous Peoples historically have been unethically exploited in the name of science. This article outlines the relationship between sovereignty and ethics in the context of data to describe the collective rights that Indigenous Peoples assert to increase control over their biomedical data. Then drawing on the CARE Principles for Indigenous Data Governance (Collective benefit, Authority to control, Responsibility, and Ethics), we explore how standards already set by Native nations in the United States, such as tribal research codes, provide direction for implementation of the CARE Principles to complement FAIR. A broader approach to policy and procedure regarding tribal participation in biomedical research is required and we make recommendations for tribes, institutions, and ethical practice.