ELSI Publications and Products Database

Obesity rates in the United States have escalated in recent decades and present a growing challenge in public health prevention efforts. Advances in genomics have begun to shed light on the genetic contributions to obesity. At present, it is unknown whether information about one's personal genetic predisposition to obesity will add value to traditional risk communication efforts and increase the likelihood that individuals will engage in health behaviors to reduce obesity risk. The clinical utility and impact of this information on psychological, behavioral, and health outcomes have yet to be determined. Research is critically needed to identify the best practices for providing genetic information to individuals regarding their risk for obesity, which may serve as a model for understanding the behavioral responses to SNP testing for common diseases. The proposed study will examine the impact of providing genetic risk information for obesity on people's attitudes and beliefs about obesity, health behaviors and weight outcomes. We will conduct a randomized controlled feasibility trial to examine the short-term impact of risk feedback for obesity, using a 2x2 factorial design. The two factors will be genetic risk feedback (no/yes) and lifestyle risk feedback (no/yes), resulting in four conditions: 1) neither genetic or lifestyle risk feedback (wait-list control), 2) genetic risk feedback only, 3) lifestyle risk feedback only, and 4) both genetic and lifestyle risk feedback combined. The specific aims of the study are to: 1) examine the effects of providing innovative genetic risk feedback, alone or in combination with lifestyle risk feedback, on participants' behavioral intentions, health behaviors (physical activity, diet, television viewing), and weight outcomes, and 2) determine the extent to which the effects of genetic and/or lifestyle risk feedback vary as a function of risk status (elevated versus non-elevated). We will also examine the mechanisms by which genetic and/or lifestyle risk information may influence lifestyle behaviors, guided by self-regulation theory. This study will be the first to obtain pilot data on the short-term (mechanism-focused) impact of providing obesity genotype feedback on actual behavioral outcomes among both overweight and non-overweight individuals. Because this is a pilot study, data will be used to develop effect sizes and variance estimates to be used in planning a larger randomized trial. We will determine the "value added" of genetic information when combined with lifestyle risk feedback, and whether it enhances motivation to engage in healthy lifestyle behaviors. Moreover, we will also determine whether providing "low risk" genetic feedback has any adverse effects (e.g., false reassurance). Finally, this study is uniquely situated to provide important data on how individuals interpret different sources of risk information and how they arrive at an overall perception of risk for a condition. Taken altogether, study findings will be used to serve as an overall model for future intervention efforts to effectively communicate genetic risk information with the goal of improving weight management and overall population health. 1 PUBLIC HEALTH RELEVANCE: Although genetic testing for obesity is widely available to the public through direct-to-consumer companies, little is known about the impact of this information on people's attitudes towards obesity, health behaviors, and weight outcomes. This study will examine the feasibility of using obesity-related genetic information to motivate individuals to reduce their risk for obesity. Study findings will serve as an overall model for future intervention efforts to effectively communicate genetic risk information with the goal of improving weight management and overall population health.

With the dramatic reduction in the cost of whole genome sequencing (WGS), genomic data are becoming increasingly available and have the potential to advance public health and promote personalized medicine. However, human genomic data usually carry sensitive personal information making data owners cautious about sharing it and genomic privacy is emerging as a big challenge for the entire biomedical community. In this proposal, we will develop novel methods for genomic privacy protection, which will facilitate genomic research. Our first aim i s to develop privacy-preserving and efficiency-oriented computational models for processing, sharing, and storing genomic data in a cloud-based environment. This aim relies on scalable cryptographic techniques, joint compression, and encryption schemes, as well as leverage of high-performance computing architecture to achieve privacy-preserving analysis and storage efficiency in the cloud. The second aim i s to develop trustworthy computational models that enable researchers to analyze distributed genomic data without requiring patient-level data exchange. These aims are devoted to the mission of the National Human Genome Research Institute (NHGRI) to develop resources and technology that will accelerate genome research and its application to human health. The NIH Pathway to Independence Award provides a great opportunity for the applicant to complement his computer engineering background with biomedical knowledge, and specialized training in genomic analysis, genomic privacy, as well as high-performance computing. It will also allow him to investigate new techniques to advance genomic privacy protection. The success of the proposed project will help his long-term career goal of obtaining a faculty position at a biomedical informatics program at a major US research university and conduct independently funded research in the field of genome privacy. Public Health Relevance The proposed research will develop practical methods to support privacy-preserving genomic data analysis, and leverage parallel computing for secure and efficient data access. The development of such privacy technology may increase public trust in research. The privacy technology we propose will also contribute to the sharing of genomic data in ways that meet the needs of those in biomedical research.

This is a competing renewal to continue our investigations of the use of molecular cytogenetic testing by array copy number analysis in prenatal diagnostic testing. We have completed a prospective blinded comparison of copy number analysis (aCNA) with standard conventional karyotyping in 4400 unselected prenatal diagnostic tests. Our work demonstrates that aCNA identifies all pathologic findings seen by karyotyping and provides significant incremental information in 2% of all patients tested. These findings make it highly likely that aCNA will become an important part of prenatal diagnosis. However, important additional information is still required to assure a smooth transition to this new method. Our initial work has demonstrated a major need to improve our understanding of the natural history, reentrance and expressivity of copy number variants when discovered in-utero. To accomplish this, we will identify and recruit over 650 mothers with a prenatal diagnosis of a copy number variant in their fetus. Detailed developmental evaluations will be conducted at age 3 on over 400 recruited during the first two years of the project. For the more common copy number variants associated with neurocognitive abnormalities, sibling controls will undergo similar evaluations to allow quantitative comparisons. The data from all participants will be included in a national registry of copy number variants and will be available for clinical and research use. A web-based resource center will be developed providing patient support and information, as well as a supplementary means of recruitment. This study will also evaluate the counseling and educational implications of copy number analysis as it is introduced into care. Evaluation of patient and counselor experiences and attitudes will be performed leading to the development of appropriate pre and post test guidelines and educational materials that will be disseminated through an online resource center. PUBLIC HEALTH RELEVANCE: Molecular cytogenetic technologies have proven to have significant advantages over conventional karyotyping and are becoming an increasingly important part of clinical medicine. To assure appropriate transition into prenatal diagnosis we must have an improved understanding of the natural history of small genomic imbalances when discovered in-utero. Detailed study of patient and provider responses to this transition will give us an important understanding of the counseling and educational requirements needed as increasingly more sophisticated genetic evaluations are introduced into patient care. AIM 2) Evaluate the educational, counseling and psychosocial implications of microarray testing as it is introduced as a standard prenatal diagnostic procedure: Whenever a new diagnostic test is introduced into clinical practice, a period of learning and transition is necessary. This is especially the case with copy number analysis, since the implications of the findings and subsequent clinical decisions are significant. Array design, appropriate pre- and post-test counseling, and indications for testing require evaluation of patient and practitioner attitudes and experiences. As part of our NICHD microarray project, a pilot ancillary study to identify and prioritize these issues was performed. Based on these initial findings, a more robust study is required to further evaluate the educational, social, and psychological implications of array testing in prenatal diagnosis. To address this aim, we will survey and interview both patients and providers. Results will serve as the framework for developing clinical and counseling guidelines, and will provide the basis for educational materials that will be developed, evaluated and disseminated by the Resource Center created through this project.

This study will examine the significance accorded to disability in judgements about quality and value of human lives, focusing on two domains in which such judgments are of central importance prenatal testing by prospective parents, and the use of disability-adjusted life years (DALYs) to determine the cost-effectiveness of health care interventions. To address these issues, the investigators will convene an interdisciplinary working group of researchers with backgrounds in philosophy, law, genetics, counseling, public health, economics, and social science. The group will —> analyze the extent to which the justifications for actual and proposed uses of prenatal testing and DALYs rest on controversial assumptions about disability and quality of life, and debate the validity of those assumptions; and —> in response to these concerns, consider proposals to regulate or limit the availability of prenatal testing for the purpose of selective abortion, and the use of DALYs for the allocation of scarce health care resources.

This project would address several questions concerning parental rights and responsibilities in forming families and the morality of using genetic technology to prevent or create children with impairments: 1) Are genetic impairments subject to greater concern than other alleged sources of harm to future children? If so, is that greater concern justified? 2) Do public attitudes, practices, and policies toward reproductive conduct take account of whether that conduct affects the identity of the future child? Should they? 3) Can we reconcile our attitudes, practices, and policies toward: a/ the use of genetic technologies to select allegedly harmful genetic features or the failure or refusal to select against those features; b/ the use of those technologies to select "positive" or desired genetic features; c/ the use of reproductive technologies that create children with unclear lineages and unconventional family structures; d/ the risk of harm to future children arising from such activities by pregnant women as high-risk employment and heavy alcohol consumption; and e/ the risk of harm to existing children arising from deficient, neglectful, or abusive parenting. In addressing these questions, the investigators would employ conceptual and ethical analysis, informed by a close review of the relevant empirical and policy literatures.

The goal of the project will be to address and clarify the methodological, legal and philosophical issues raised by research on genetic factors in crime, and to introduce the public to this emerging debate. The project will convene a conference in the Fall of 1992 to bring together —> researchers investigating the genetics and neurobiology of criminal, violent and impulsive acts, and of related behavioral and psychiatric disorders; —> historians, sociologists and philosophers who will put the scientific research into historical, cultural and intellectual perspective; —> criminal justice specialists who will gauge the impact of this research on criminal investigation and adjudication; and —> legal scholars and moral philosophers who will discuss how the discovery of genetic predispositions may affect our practice of punishment and our conception of moral responsibility. The conference organizers will videotape the proceedings for distribution to the media and educational groups, produce a special conference issue of The Report from the Institute for Philosophy and Public Policy, the Institute's widely-read quarterly, circulate conference papers as part of the Institute's Working Paper Series, and edit an anthology of conference papers for publication.

Obtaining valid consent for the collection and storage of biospecimens and data for future, unspecified research use remains a significant challenge. Numerous studies have documented that research participants in a variety of settings-including biobanking-do not understand important aspects of the research to which they consented. To correct this problem, two major challenges must be overcome. First, there is no consensus on what constitutes 'adequate' understanding in biobanking consent, creating uncertainty about when valid consent has been obtained and hampering efforts to devise and assess interventions to improve comprehension. Second, the overall quality of the evidence concerning the effects of interventions to enhance comprehension is poor. Prior studies have suffered from small sample sizes, non-randomized designs, limitations related to the characteristics of the study population, questions about how 'comprehension' was defined and measured, and a narrow focus on only selected elements of the consent process. Given the ubiquity of biobanking research, there is a critical need to overcome these challenges by defining the threshold of knowledge needed to provide truly informed consent, and developing and rigorously studying interventions to promote comprehension in the context of a complete informed consent process. Our objective for this application is to develop and assess an informed consent process for biobanking that involves a simplified consent form and an interactive test/feedback procedure to enhance comprehension. To achieve this objective, we will pursue the following aims: (1) Systematically determine the threshold of knowledge needed to demonstrate adequate biobanking consent comprehension; (2) Refine a teach-back tool to improve comprehension during the biobanking consent process; (3) Conduct a national, multisite, randomized trial to determine the individual and combined effects of a teach-back intervention and a simplified consent form on comprehension in biobanking consent; (4) Explore the individual and combined effects of a teach-back intervention and a simplified consent form on secondary consent process outcomes. The expected outcomes include a systematically-developed definition of 'adequate' understanding and high quality data demonstrating the effect of improvements to forms and processes on biobanking consent comprehension, as well as model consent forms, teach-back tools, and measures that could be readily adapted for use in any biobanking context. PUBLIC HEALTH RELEVANCE: Many potentially high-impact research initiatives are significantly hindered by the limited availability of high- quality biospecimens and data. Ensuring that valid informed consent is obtained by accurately assessing and promoting comprehension is critical for protecting the rights and welfare of participants as well as preserving the integrity of research involving biobanking. The successful completion of the proposed study will lead to significant improvements in the way informed consent is conducted and evaluated for biobanking research.

Problems in international cooperation may arise if genetics centers in different nations operate under different ethical standards. A survey will be conducted for the HGP. Geneticists in 34 nations will receive the same questionnaires as those used in the U.S. - Canada survey described above. In each nation, a contact geneticist will distribute the questionnaires. Results reflecting geneticists' own views about preferred legal/ethical approaches will be useful to policy-makers and lawmakers in all nations involved in the HGP. This study is serving as an extension of the above study of 1600 geneticists and genetic counselors. Results will be compared with responses from the national study.

1600 geneticists and genetic counselors in the United States and 100 in Canada will be surveyed to determine their attitudes toward ethical dilemmas in genetic counseling, screening, and prenatal diagnosis situations. 900 obstetricians, pediatricians and general practitioners will receive similar questionnaires. 1300 patients at clinics in the U.S. and Canada will receive questionnaires before and after counseling. 1000 members of the general public will be surveyed by the Roper Organization, using 20 questions from the patient questionnaire. The data will make possible comparisons between geneticists, other professionals, patients, and the general public. The questionnaires will be anonymous. Questions presented as case vignettes will focus on the following issues related to the HGP: informed consent; access to test results by family members and third parties; the right 'not to know' test results; ownership of DNA; DNA banking; workplace screening; screening for susceptibility to common disorders; DNA fingerprinting; prenatal testing for late-onset disorders; eugenics; and testing children for adult-onset disorders.

While many of the ethical, social, and legal issues which human genome research create can and should be debated and resolved within the borders of particular countries and regions, there are a number of issues which cannot be satisfactorily resolved without international understandings, negotiations, and accords. This group includes: international sharing of research burdens, benefits, and information; use of genetic information by the police and military; use of genetic information in identification of racial groups and in eugenic initiatives; and responsibilities of HGR scientists worldwide in determining the direction of their work. This conference will bring together approx-imately 40 scientists, officials, and ethicists from around the world to prepare an agenda of these issues for consideration by the appropriate national and international agencies. The conferees will compare views on the need for international cooperation on a number of issues and attempt to reach consensus on which issues require international accords and which do not. The resulting agenda for international action will be drawn up and published under the supervision of the planning committee.

Primary care physicians have almost no training in genetics, nor in the ethical, legal and social implications (ELSI) of genetic testing, diagnosis and therapy. Further, mere provision of curricular content fails to impact physician behavior. However, programs with elements that are based on established educational and adult learning principles have been shown to effective in affecting behavioral change. We propose to evaluate whether participation in a web-based curriculum focusing on the ethical legal and social issues in primary care genetics will improve primary care physicians' approach to genetic issues. Specifically, we will assess whether participation will improve physician knowledge, attitudes, and practice-behaviors. We will recruit 120 PCPs across five health systems in California (UC Davis, Rural Health Network, UC Los Angeles, Kaiser Permanente, Sutter Medical Group Sacramento). PCPs will be randomized by practice site to control (paper curriculum) or active intervention with an interactive web-based curriculum previously developed with funding from the NHRGI. This curriculum utilizes visual tools, video clip vignettes, and other interactive content to illustrate key points about risk assessment, genetic screening, and SDM. PCPs encounters with Announced Standardized Patients Learning objectives will be used to assess PCP's ELSI related behavioral change. Evaluation will also include the effectiveness of the curriculum for genetic knowledge (testing of knowledge), skills (self-report, follow-through with learning plan), and attitudes (survey and self-efficacy assessments). If proven effective, these web-based tools can be easily disseminated around the country, and internationally, to improve knowledge and attitudes about genetic screening among physicians and patients. PUBLIC HEALTH RELEVANCE: Most primary care physicians have almost no training in genetics, nor in the ethical, legal and social implications (ELSI) of genetic testing, diagnosis and therapy. This project evaluates a novel web-based curriculum focusing on the ethical legal and social issues in primary care genetics in order to improve primary care physicians' understanding of the implications of genetic disorders in patients' lives. If proven effective, these web-based tools can be easily disseminated to improve physician's knowledge of the social context of genetics and improve their ability to engage in shared decision-making with patients about genetic screening.

This conference will provide for an exchange of information about the scientific, clinical, and societal issues associated with the application of biotechnology assays to the diagnosis of genetic disease. Its purposes are to focus on the policymaking implications of new biotechnologies at the federal level; assist the FDA in determining criteria for evaluating safety and efficacy of the technology; provide information for manufacturers to use in developing clinical trials; and serve as a forum for discussion among policymakers, manufacturers, researchers, clinicians, and genetic information users on the societal, economic, and reimbursement issues associated with the new technologies.

The ability to manipulate atoms and molecules at the nanoscale has catalyzed the emerging field of nanomedicine. While many biological phenomena occur at the nanoscale, "nanomedicine" denotes material fabricated at the scale of 1-100 nanometers (nm) to take advantage of novel properties (biological, optical, thermal, chemical, and mechanical) that manifest at the nanoscale. A focal area of development is nanodiagnostics and nanotherapeutics. These fields use nanotechnology to develop nanoscale tools for in vitro diagnostics, in vivo imaging agents, drugs and therapies, targeted drug delivery systems, nanoparticle and other nanoscale gene delivery vectors, biomaterials for enhanced tissue engineering, and multi-function medical devices. Nanomedicine poses enormous challenges for human subjects research and oversight particularly because the health, safety, and environmental impacts of nanomaterials are largely unknown and researchers are struggling to characterize these materials and develop adequate toxicology and assessment tools. Despite these unknowns, research on nanodiagnostics and nanotherapeutics is already being conducted with human participants. Institutional Review Boards (IRBs), Data Monitoring Committees (DMCs) and Data Safety Monitoring Boards (DSMBs), funders such as the National Institutes of Health (NIH), and oversight authorities at NIH, the Food and Drug Administration (FDA), and Office for Human Research Protections (OHRP) are already facing acute challenges posed by nanomedicine research, but without systematic guidance on how to address those challenges. Indeed, the FDA has already approved some nanomedical products for use in human beings. Work is urgently needed to address what substantive changes to the rules governing human subjects research and what procedural changes to research oversight are necessary. This 2-year project will examine current and emerging nanomedicine research on drugs, devices, and gene therapy in order to map the issues raised by nanodiagnostic and nanotherapeutic research and oversight and formulate much-needed guidance. We will collect and analyze existing guidance on human subjects research and oversight by the NIH, FDA, and OHRP in nanotherapeutics and nanodiagnostics as well as existing policy analysis. We will use that to inform normative work generating the first systematic recommendations to ensure adequate protections and oversight for human participants in nanomedicine research. This process will involve collaboration among Investigators and Working Group members who are directly involved in the science, medicine, policy, law, and ethics of nanotechnology. This project will have major impact by providing the first systematic and comprehensive guidance on the ethical conduct and oversight of human subjects research on nanotherapeutics and nanodiagnostics. Outcomes will be: (1) an assessment of publicly available documents indicating how researchers, IRBs, DMCs/DSMBs, NIH, FDA, OHRP, and relevant professional societies are currently approaching the ethics of human subjects nanomedicine research; (2) an assessment of how NIH (including the Office of Biotechnology Activities (OBA) and the Recombinant DNA Advisory Committee (RAC)), FDA, and OHRP are approaching the oversight of human subjects nanomedicine research; (3) the first comprehensive and systematic recommendations on the ethics and oversight of human subjects nanomedicine research, to be authored by the Investigators after critique by the Working Group; (4) additional individually authored papers by members of the Working Group; (5) a public conference with videotape archived for free public access; (6) a comprehensive bibliography; and (7) rich web-based resources. This proposed project will serve the goals of ARRA by creating 4 jobs and significantly augmenting a fifth to aid in retention of that job. This project brings together top experts on nanomedicine, biomedical engineering, law, policy, and bioethics to produce the first systematic and comprehensive recommendations on how to protect human participants in research on nanodiagnostics and nanotherapeutics, including drugs, devices, and gene therapy using nonviral nano- vectors. Research in these nano-fields is burgeoning, with research on human participants under way, but current research ethics and oversight have not yet adequately addressed key concerns including: difficulty predicting human response from animal data, uncertainty about how to assess risks, concerns about both participant and third-party safety both short-term and long-term, and challenges obtaining informed consent. The project group will use normative, empirical, and policy analysis to evaluate current approaches to nanomedicine research ethics and oversight, including at NIH, FDA, and OHRP, generating much-needed recommendations on ethics standards and oversight processes.

This 2-year project tackles a profoundly important but widely ignored problem: how should researchers handle incidental findings that have potential clinical significance, what should consent forms say about this, and how should IRBs consider the potential for incidental findings in their review of protocols. By "incidental findings" we do not mean results on those variables of key interest in the research, but unexpected findings beyond the domain of focal research interest, such as a suspicious mass revealed in a functional MRI (fMRI) study, or an incidental finding of nonpaternity in genetic research on families. We will anchor our analysis by focusing on incidental findings in 4 research areas: (1) fMRI research, (2) CT colonography research, (3) genetic research on families, and (4) genomic microarray research. This project will have a normative and an empirical component. The normative work will focus on developing a consensus paper on how incidental findings should be managed by investigators and IRBs and model consent form language. This will be informed by collection and analysis of model consent forms and consent forms used by U.S. researchers in the 4 areas of study as posted on university, professional society, and governmental websites and on the World Wide Web. This project will be led by researchers in the University of Minnesota's Consortium on Law and Values in Health, Environment & the Life Sciences, collaborating with a senior empiricist expert in content analysis and a Working Group of prominent national scholars. Project outcomes will include: publication of the consensus recommendations and model consent form language, a conference presenting our conclusions plus papers on incidental findings management in the 4 targeted research areas and analysis of the legal implications of incidental findings, a published symposium in a prominent journal collecting these papers, and a website offering tools such as model consent form language and an annotated bibliography with web links.

This 2-year renewal project builds on our previous NHGRI-funded project on "Managing Incidental Findings in Human Subjects Research" (#1 R01 HG003178-01A1). Using that project's outcomes as a foundation, we now propose a 2-year renewal project to address one of the most pressing issues facing genomic research: What information, if any, about incidental findings (IFs) and individual research results (IRRs) should be offered back to the individuals whose DNA and data are collected and housed in genomic biobanks and archived datasets? We will convene a multidisciplinary Working Group in order to develop normative consensus recommendations on managing IFs and IRRs in genomic research using biobanks and large archives. There are 10 components to this project: (1) identification of U.S. biobanks (defined in this project to include datasets and DNA samples archived for reanalysis) and websites where available; (2) collection of the relevant literature, guidelines, law, and regulations, including international guidelines and statements on biobank management; (3) collection and content analysis of biobank websites (including policy statements, consent forms, FAQs answers, and other informative material) to analyze approaches to IFs and return of IRRs; (4) collection and content analysis of relevant documents by emailing the manager or director of biobanks identified, including those with no or uninformative websites; (5) collection and content analysis of relevant non-U.S. documents from the websites of major international (non-U.S.) biobanks with websites in English and by email to the manager or director of each biobank; (6) development of normative consensus recommendations providing guidance on how to handle IFs and return of IRRs in genomic biobank research and soliciting feedback; (7) authorship of targeted analyses of this problem and the legal aspects; (8) presentation of consensus recommendations and targeted analyses at a public conference for feedback; (9) publication as a symposium in a prominent journal; and (10) development of a publicly available website containing tools for biobanks, their ethics oversight bodies, IRBs, researchers, research participants, scholars, and others on managing IFs and return of IRRs, including an annotated bibliography with web links. To accomplish this, the project will involve 3 methodologies: (A) a normative process to reach consensus on how IFs and IRRs should be managed in genomic research involving biobanks and archived samples and data, supported by (B) empirical and analytic research systematically collecting the relevant literature, guidance documents, regulations, and law, with structured content analysis of (a) the policy, informational, and consent documents publicly available on biobank websites, and (b) additional documents collected by email query from biobank managers and directors, and (C) international comparison of the policies on return of IFs and IRRs among major DNA biobanks with English-speaking websites. PUBLIC HEALTH RELEVANCE: In order to understand the genetic contribution to a host of diseases and conditions of great importance to public health, scientists are increasingly assembling large biobanks archiving many individuals' DNA and health information for scientific reanalysis over time. However, there is no clarity about what individual health information, if any, should be given back to those people generous enough to donate; some prominent biobanks are giving back none at all. This project will convene leading experts on bioethics, genomics, biobanking, and law to recommend ethical policies and practices on return of both incidental findings and individual research results that may have importance for the donor.

Exome sequencing (ES) and whole genome sequencing (WGS) are transformative new tools for discovery of genetic risk factors for both rare and common diseases and offer the potential of personalized genetic risk profiling in a single, cost-effective test. Because of the large number of variant results simultaneously identified, the number of results with potential clinical utility-including those that are unanticipated, and the evolving utility of results over time-use of these technologies challenges existing models of returning results to research subjects and patients. This has generated widespread interest in developing and testing innovative strategies for returning results from ES/WGS studies. Almost all strategies currently being studied, however, focus on returning results to European Americans-despite evidence of differences among racial and ethnic groups for preferences for results, the interpretation of clinical utility, and the impact of receiving geetic results. This situation reflects the broader challenge of involving racial and ethnic minority communities in genetic research in order to ensure parity in the benefits of advances in genomic medicine. Accordingly, it is imperative that we understand the attitudes and preferences of racial and ethnic minorities toward genomic research and specifically return of ES/WGS results, and assess the outcome of receiving ES/WGS and its impact on minority participation. I am choosing to devote my career to further the ethical and scientific translation of genomics to benefit all people, especially underserved racial and ethnic minorities. Through formal training at leading research institutions, mentored research and publications with experts in their respective fields, I will capitalize on my prior training in public health genetics and complete my transition to an independent investigator by (1) acquiring skills in quantitative survey development, conduct, and analysis;(2) acquire skills to work with culturally diverse racial and ethnic minority communities to conduct collaborative research;and (3) broaden my understanding of theoretical and empirical work on group harms and benefits from bioethics, anthropology and the social sciences. To compliment my formal training, I will utilize these skills to conduct two mentored research projects including (1) a survey of healthcare providers and community leaders who serve racial and ethnic minority communities and (2) focus groups with racially and ethnically diverse adults, about participation in genetic research and return of ES/WGS results. In the independent phase of this proposal, I will (1) characterize and describe attitudes of underserved populations toward return of ES/WGS results by using a survey and (2) characterize individual preferences for receiving ES/WGS incidental finding through interviews with participants who are using a newly developed web-based tool called My46. Also using this tool, I will (3) study the outcomes of returning ES/WGS incidental findings to a cohort of African American individuals. Public Health Relevance Exome sequencing (ES) and whole genome sequencing (WGS) are transformative new tools that are revolutionizing gene discovery for Mendelian disorders and complex traits. The prospect of participating in ES/WGS research and returning results from ES/WGS presents numerous challenges including the need to ensure equal benefit to underserved racial and ethnic minority populations, and the potential for group benefits and harms. I propose to learn about the perspectives of racial and ethnic minority populations on participation in ES/WGS research and receiving ES/WGS results.

The Board on Biology of the National Research Council's Commission on Life Sciences is conducting a study of standards for forensic DNA typing. The development of recombinant DNA and other laboratory techniques to analyze complex genomes has resulted in an increasing array of procedures that have potential forensic applications. What once were basic laboratory techniques used to study genetic variability are now being used to link suspected criminals to crimes and to resolve paternity disputes. The potential also exists for developing computer databases consisting of information on an individual's DNA characteristics. Such a database could be used in a manner similar to established fingerprint databases. Issues surrounding the suitability of these techniques for forensic and other law enforcement purposes, including the general applicability of these techniques for forensic purposes, the need for acceptable standards, the development and application of supporting technology and instrumentation, an understanding of the statistics and population genetics required in interpreting DNA typing data, and the societal, legal, and ethical implications should be evaluated.

A full day public education forum on the HGP, to be held in 1992, is being planned as part of the Choices and Challenges forum series at Virginia Tech. This series was established in 1985 to provide public audiences with information about recent scientific and technological advances and to explore social and ethical issues related to these advances. The one day forum on the HGP is designed with three separate components: tutorial and briefing groups that will provide scientific, historical, and ethical background; a plenary session, that will be teleconferenced nationally; and a post-plenary portion, concluding the program with in-depth discussions involving the presenters and the audience. Forum videotapes, newspaper articles, and public service programs, based on the conference, will foster continued community-wide consideration of the HGP.