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Advances in psychiatric genetics are likely to offer major diagnostic and therapeutic benefits, but also legal and social-related risks, to individuals who were diagnosed with, or have a proclivity for, psychiatric disorders. In response, courts and policy-makers will have to ensure that psychiatric genetic data are used to promote, and not to obstruct, equality, justice, and social inclusion. However, few studies have queried how such data might impact judicial decision-making; none have explored this question in civil proceedings about parental rights, children's education, and responsibility for behavior in tort. This K01 proposes to study the impact of psychiatric genetic data on these 3 prominent areas of litigation and its relationship to stigma to better understand the implications of new discoveries in psychiatric genetics for law, society, and individual rights, and to inform policy-makers about this knowledge as they devise responses to these advances. The study's aims are: 1) To survey appellate court decisions in family law, education, and torts to determine the extent to which courts are considering psychiatric genetic data, and how they use such data in their decisions; 2) To investigate judicial views about the use of psychiatric genetic data and how such data may affect judges' and public perceptions of parental capacity, educational decisions, and civil responsibility for behavior in tort cases; and 3) To assess the association between psychiatric genetic data and stigma by studying if such data affect judges' and public perception of broader civil legal incapacity and treatment options, and the relationship to judicial bias against persons with psychiatric conditions. For Aim 1, I will use a mix of qualitative legal analysis and empirica methods. For Aim 2, I will use a vignette methodology, administered in 3 waves, with samples, respectively, of family court judges, parents, and state trial court judges and the jury-eligible general population. For Aim 3, I will use existing legal and sociological literature on psychiatric related stigma to develop measures of explicit stigma, and a computer-based measure designed to detect implicit bias, administered as part of the vignettes, to assess the relationships among psychiatric genetic data, judicial decisions, and stigma. Findings will be published in peer-reviewed medical, psychological and policy journals. Complementing these studies will be an intensive training program comprised of didactic courses, tailored training, clinical exposure at the NY State Psychiatric Institute, and mentored experience. My primary mentor Dr. Appelbaum, co-mentors Drs. Link and Ottman, collaborator, Dr. Phelan, biostatistician, Dr. Goldsmith, and consultant, Dr. Parens will train and monitor my progress as I attain my training goals to: 1) develop the skills necessary for conducting empirical research; 2) learn about the clinical aspects of psychiatric disorders; and 3) build and expand national and international professional collaborations with scholars in psychiatry, genetics, social sciences, bioethics, and law. This training will culminate in R01 grant submission to further study the intended and unintended consequences of psychiatric genetic data on law, equality, and social inclusion.

The proposed research seeks to analyze arguments in the literature of philosophy, theology and public policy that take the genome in its integrity, contingency, or historical authenticity to be what ground humanity as natural or as part of nature. According to this view, insofar as human beings deliberately alter or control the human genome, they alienate themselves from their evolutionary history and from the natural world. The idea is, in effect, that humanity remains a part of nature as long as nature - in the form of non-manipulated genome - remains part of humanity. The proposed study will examine the form of 'genetic exceptionalism' that invokes the concept of 'nature' and the 'natural' judgments, usually critical, concerning the manipulation of the human genome. The researchers would then evaluate arguments that -- on the basis of the relation between nature and the genome -- support restriction on genetic engineering. Specifically, the research team will 1) analyze the extent to which criticisms and concerns about the instrumental manipulation of the human genome rest on controversial assumptions about nature, human nature, and the connection between humanity and nature; and it will assess the validity of those assumptions. The project, will 2) produce a series of essays to be collected into a book, along with other articles, conference presentations, and policy-related papers, all of which will evaluate proposals that appeal to conceptions of nature as reasons to regulate or limit or ban various applications of genetic engineering.

The proposed project seeks to provide conceptual and normative analyses of three ideas that are often invoked in debates over the prospects of human genetic engineering. These concepts are: 1) "Homo sapiens" (a biological species concept); 2) "person" (an ethical and a legal concept); and 3) "human being" (a cultural and aesthetic concept). The Investigators believe that philosophical clarification of these concepts as they arise in debates over the possibility of technological interventions into the human genome can strengthen contemporary discussion of ethical, legal, and social implications of the Human Genome Project. The project would review and assess the growing literature on germ-line intervention and human nature in relation to the differences among these three concepts. The project would produce philosophical analyses that will explicate possible limits on germ-line engineering that may be justified in terms of maintaining the character or status of individuals as members of a historical species, as possessing free will or moral responsibility, and - most importantly - as sharing a cultural identity as human beings. The project aims specifically 1) To analyze the properties associated with human nature - or the aspects of our shared humanity - that restrictions on germ-line engineering may seek to protect or preserve; 2) To show how assumptions about human nature can be analyzed and clarified in terms of logical relationships among three different concepts: Homo sapiens, human being, and person; and 3) To produce a series of essays to be collected into a book, along with other articles, conference presentations, and policy-related papers, which will analyze and evaluate proposals that appeal to any of these three concepts as normative principles or reasons to ban or regulate applications of genetic technologies to the human genome.

The proposed project will determine the factors with which people distinguish genetic from non-genetic disease, and the factors that they bring to bear in interpreting genetic diseases or conditions. The project will identify the ways in which these factors might vary between the following three contrastive pairs: —> people who are members of racial or ethnic groups that historically have been subjected to stigmatization, versus those who are not; —> scientists who conduct this research, and the lay public who it may concern; and —> people who have a known genetic condition, and those who do not. We will explore these questions with two studies: —> Study 1 is a face to face guided interview that includes open-ended questions and card sorts; —> Study 2 is a questionnaire, that includes a Social Stigma Scale and an Attribution of Genetic Difference Scale. The project goals are to determine the variety of factors people bring to bear on interpreting genetic conditions, the circumstances that encourage stigmatization, and to test the hypothesis that stigmatization occurs more often among people who are members of populations that are already stigmatized.

The overall goal of the proposed research is to contribute to improved communication about race and ethnicity among genetics researchers and, as a result, between these researchers, professionals who are meant to apply the results of research on human genetic variation, and the public. Our primary aim is to clarify how and why researchers use race and ethnicity in forensic and medical genetic research, and what researchers think are appropriate generalizations and applications of their findings. A secondary aim is to familiarize graduate students from genetics and social science with the meanings and functions of race and ethnicity in different disciplines. Our research will include a national survey of medical and forensic genetic researchers, in-depth interviews, and a content analysis of genetic research articles published in peer reviewed medical and forensic genetic journals. Through short-term summer internships, we will involve an interdisciplinary group of graduate students in this research and facilitate among them understanding of multiple perspectives on the relationship of genetics with race and ethnicity. A belief that there exists a single correct definition or function of race and ethnicity in genetics research does not motivate the proposed study. Nor is the intent of this research to contribute to the debate over biological phenomenon associated with genetic variation. Rather, the motivation is to address the inconsistencies of terms used in genetic variation research in order to enhance scientific validity and generalizability, and to facilitate clear communication among scientists and with the public. If the debates continue without clarification on how to resolve them within the research community, there is a real danger that genetics and medical research generally will be slowed if the public perceives that science is contributing to discriminatory ends, even if that is not the scientist's intention.

In the context of the Human Genome Project, this project will attempt to clarify reductionist claims respecting human physical and complex mental and behavioral traits. It will analyze the nature of genetic reductionism and provide a method for resolving controversies over claims of the reduction of traits. In a conceptual clarification of genetic reductionism, the investigator will distinguish genetic reductionism from physical reductionism and place these concepts within the context of causation and explanation theories and heredity-environment debates. Next, the project will trace the history of genetic reductionism in 20th century biology and attempt to judge the probability of success of the application of the theory of genetic reductionism to the Human Genome Project. This history of reductionism will be related to eugenics and a tentative list will be developed of cases where a claim of genetic reductionism is justified and cases where it is not. The purpose of this list will be to shed light on the more difficult and controversial cases of genetic reductionism, including complicated human psychological traits.

The purpose of this project is to address the professional dilemmas of nurses related to genetic information about patients and their families. Continuing education in genetics is not widely available for nurses, and there is currently no credentialing process for advanced levels of nursing practice in genetics. The objective of this project is to survey a national sample of practicing nurses to obtain accurate information about the ways in which nurses are currently eliciting, using, and storing genetic information about patients and their families, and to identify the ethical dilemmas that nurses face in their various roles in the identification of genetic traits, chromosomal abnormalities, and diseases with a clear genetic basis.

The purpose of this project is to analyze the boundaries of 4th Amendment search and 5th Amendment self-incrimination jurisprudence in light of the developing ability of the police to mine a human's cells for increasingly private, personal and powerful genetic information. Forensic technology already provides a hazy genetic photograph of a suspect - a genetic nametag, bio-geographical continent of origin, skin pigmentation and eye color. Ongoing behavioral and disease genetics research and the allure of the $1,000 genome is speeding us towards an even larger forensic treasure-trove of individuating genetic characteristics. The project will explore discarded, latent and new themes in 4th and 5th Amendment privacy jurisprudence in an effort to answer three questions: (1) Do we want to continue to allow the police to mine for any genetic information the cells of anyone who has abandoned those cells in a public place? (2) Do we want to continue to allow the police to compel anyone to offer up those information-laden cells without regard to the person's right against self-incrimination? (3) If we do not, how can and should we change the 4th Amendment search and 5th Amendment self-incrimination privacy paradigms to account for our changing conceptions of identity and self? The project will answer these questions through an extensive and creative review of traditional 4th and 5th Amendment jurisprudence and an attention to developing forensic, behavioral and disease genetics trends. The project will result in at least two articles in legal journals and presentations to professional, judicial and academic groups. This project aspires to think now in a disciplined and creative way about how well current 4th and 5th Amendment constitutional doctrine will be suited in the future to address circumstances in the world of police investigation that we are only beginning to imagine.

The goal of this project is to study an historical precursor and parallel to the HGP: the discovery of the inheritance of the ABO blood system and the attempt to use it as a genetic marker for a variety of human traits and disorders. The literature published during the period from 1919 to 1939 will be analyzed based on research done world-wide on blood group distribution as a definition of race and the links between blood type and criminality, insanity and disease. Articles will be coded for several variables to permit statistical analysis of the overall pattern of research. Archival material of the major researchers will also be consulted to give greater depth to the picture that emerged. At least one follow-up study will be done on the period after the Second World War concerning how misapplications were recognized in attempts to define races. The anticipated result of the study is to provide human genome researchers and policy makers with a broader historical perspective that will help them recognize the new ground they are breaking while avoiding the pitfalls of similar experiences in the past.

In 1907, Indiana implemented the world's first eugenic sterilization law. The upcoming centenary of this act provides an opportune time to evaluate the far-reaching significance of this event. The Indiana law, along with similar state legislation and activities at the local level, has left an extensive record resulting from public policy based on specific ideas about heredity. The name given to these activities, eugenics, is generally known, but research about it at the state and local level has only recently begun. The overall goal of this project is to take advantage of this centenary to explore the largely untold history of state and local eugenics in the United States by conducting research that both deepens our understanding and helps draw lessons for academic scholars in bioethics and the humanities, scientists, health administrators, policy specialists, and the public. With this overall goal in mind, our specific aims are: To explore the largely untold history of sterilization and eugenics in Indiana in the twentieth century; To conduct original research on the history of eugenics by both junior and senior scholars from the fields of history, bioethics, and health policy, using a comparative and collaborative methodology; To produce an edited volume that seeks, for the first time, to compare and tell the detailed and varied history of eugenics in America at the local and state level, with particular attention to the relevance of this history to contemporary issues in human genomics, public health genetics, and reproductive health; To disseminate this research in public forums including a major public symposium in Indiana and at meetings held by organizations of health practitioners and policy makers; To help set the future agenda for research on the history of eugenics, the most widely cited yet least understood historical use of genetics in a non-healthcare setting.

This pilot project explores the values, attitudes and beliefs of affected adults and parents of affected youths about genetic testing for obesity. Obesity is an extensive problem in health care, with a rapid rise in prevalence among both adults and children during the last decade. This highly stigmatizing condition has proved especially difficult to treat in adults using behavioral approaches. Recent evidence suggests it may be genetically encoded, and in the future, genetic tests may be useful for identifying appropriate pharmacological treatment and/or for preventive screening. Diet and activity habits that lead to obesity are often formed during adolescence or earlier. Therefore we will ask adults, particularly young adults, to reflect on what their valuations would have been at a younger age, as well as parents of obese children to discuss how best to explore obesity genetic testing in a sensitive, relevant way. Goals are to identify constructs for a future model of factors that increase likelihood to pursue obesity genetic testing, and to frame issues of informed consent. This project brings together the fields of medicine, ethics, genetics, and social science. The methodology is a series of 11 focus groups of affected adults and parents of affected minor children, supplemented by their preliminary and exit survey data. End products will include —> a draft survey for use in larger, quantitative studies; —> testable hypotheses for future studies; and —> a preliminary framework of information for drafting future policy guidelines for informed consent, including ways consent may vary depending on recipient's age, gender, ethnicity and social class. These characteristics may indicate differing psychosocial meanings of obesity. This pilot project represents a first step in promoting use of genetic information about obesity in a culturally sensitive way, and ensuring that behavioral genetic research is conducted in an ethical manner. We anticipate that it will provide the framework for larger proposals using quantitative methods targeted to obesity genetic testing when the time is appropriate. In turn, we expect that these projects will lead to studies of interventions combining knowledge of individual genetic and environmental factors to improve health of patients affected by or at risk for obesity.

This revised application for a Mentored Research Scientist Development Award (K01) is designed to support the career of Laura Senier, MPH, PhD, an assistant professor at the University of Wisconsin-Madison. Dr. Senier's goals are (1) to obtain additional training in population genetics, public policy analysis, and ethical frameworks governing emerging genetic technologies; (2) to build a research program that explores technical, political, and ethical barriers in translating genetic discoveries to public health poliies and programs; and (3) to become an independent investigator in the politics of research translation. Dr. Senier will accomplish these goals through a combination of formal coursework, mentored collaboration, and empirical research on state public health policy. The research plan examines the modernization of public health genetics programs in state health agencies. The specific aims are to (Aim 1a) describe the conceptual models, organizational structures, and financing solutions that state health agencies are using to modernize public health genetics programs; (Aim 1b) explore the opinions and attitudes of stakeholders about the scope and suitability of state public health genetics programs; (Aim 2a) through a comparative case study, identify the critical elements that impede or promote integration of genetics into public health; and (Aim 2b) explain how public health genetics programs vary under different structural arrangements, and show how the opinions of stakeholders influence public health genetics programming. In response to questions from study section reviewers, this revised application clarifies the sampling strategy and explains the analytic method of the qualitative comparative case study more thoroughly. The research will be based on original data collected via field observation, in-depth interviews, and archival analysis of state public health genetics activities n four states (Michigan, Connecticut, New York, and Utah). Dr. Senier has recruited an interdisciplinary mentor committee to guide her in these training and research activities. Dr. Pila Ossorio (Associate Professor of Law and Bioethics), Dr. Daniel Kleinman (Professor and Chair of Community & Environmental Sociology), Dr. Tom Oliver (Professor of Population Health Sciences), and Dr. D. Paul Moberg, (Director, Population Health Institute) will guide Dr. Senier in these endeavors. At the suggestion of study section reviewers, Dr. Nancy Cox (University of Chicago) and Dr. Peter Conrad (Brandeis University) are joining the mentorship committee to provide additional methodological guidance. Together, this committee of mentors has expertise in the emerging legal and ethical challenges in biotechnology; organizational and political barriers in science policy and health policy; and innovative research methods in comparative case study design and program evaluation research. They are eminently qualified and fully committed to assisting Dr. Senier in her multidisciplinary training, research, and career path. PUBLIC HEALTH RELEVANCE: In the past decade, some state health agencies have begun modernizing their public health genetics programs to address both new scientific discoveries and emerging ethical issues in genetics (e.g., escalating demand for clinical services, workforce development, discovery of genetic markers for chronic disease). The proposed research will identify common elements that enhance capacity in public health genomics across states, and will clarify which elements may be unique or would work only in a particular state. This research will identify guidelines that will help states modernize public health genetics programs in ways that are ethical, equitable, and cost-effective. The NHGRI 2011 Strategic Plan argues that genomic medicine will only achieve its full potential to improve health when its innovations are available to all. States are important but understudied nodes in the nation's research translation network, and in a time of grave state budgetary constraints, it is critically important that we prepare state agencies to maximize partnerships and program resources in this ambitious goal.

With recent advances in genotyping methods, specifically improvements in DNA microarrays and chip- scanning instrumentation, it is now technically possible and economically feasible to test large numbers of patients for several thousand known mutations associated with Mendelian disease phenotypes. This possibility suggests numerous clinical applications of large-scale mutation arrays in molecular diagnosis and genetic risk assessment, such as prenatal testing for the most common mutations responsible for severe genetic disorders, screening for autosomal recessive or X-linked mutations, and predictive testing for a range of adult-onset disorders. If large-scale mutation testing is to be integrated effectively into clinical care, however, several significant ethical issues must first be addressed. Large-scale mutation testing will generate an enormous amount of diagnostic information. Given the large number of mutations examined, it will not be possible to counsel patients on technical features of each individual component of a large-scale mutation array, such as false-positive and false-negative rates, as would be done in more traditional genetic testing procedures. Nor will it be possible to advise patients on specific medical interventions or confirmatory diagnostic tests associated with identifying each of several thousand possible mutations prior to testing, as frequently would be done in other situations in which genetic testing is recommended. Since large-scale mutation testing will require a departure from these and other professional standards in clinical genetics, it is vitally important that this new form of genetic testing be introduced in a deliberative manner that is informed by the expectations, needs, and values of both patients and genetic professionals. This research study will examine patient and professional understandings of diagnostic results from large-scale clinical mutation testing. Its aims are to: (1) describe the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic possibilities that should be discussed with patients prior to large-scale clinical mutation testing, and (2) characterize the attitudes and beliefs of patients and genetic professionals regarding the types of diagnostic results that should be returned following large-scale clinical mutation testing. These empirical results will be used to develop practical recommendations regarding the presentation of diagnostic results from large-scale clinical mutation testing. Systematic data on patients' and professionals' understandings of this new form of genetic testing are critically important, as these data will inform genetic-counseling practices, decisions about the return of diagnostic results, and judgments about the appropriate use of large-scale mutation testing in patient care. Narrative This research study will examine patients' and professionals' attitudes and beliefs regarding the presentation of diagnostic results from large-scale mutation testing. Systematic data on patient and professional understandings of this new form of genetic testing are critically important, as these data will inform genetic-counseling practices, decisions about the return of diagnostic results, and judgments about the introduction of new genomic technologies into patient care.

The launch of the Human Microbiome Project (HMP), and the corresponding interest in bioengineered probiotic therapies that this new NIH initiative is likely to generate, provide a unique opportunity for research examining ethical and social considerations in the introduction of new therapeutic modalities. To date, analysis of ethical and social considerations in the use of probiotics have focused on "over the counter" applications where physician involvement in the selection and administration of the probiotic is limited. As new probiotic therapies become a part of the clinician's arsenel, it is important to consider how patients may perceive and respond to new probiotic therapies that are recommended by their physicians. To be successfully integrated into patient care, it is critical that patient attitudes and beliefs regarding bioengineered probiotics be well characterized. Studies of patient perceptions of therapeutic probiotics may reveal common misconceptions about probiotic therapies and/or widespead concerns that may limit patient enthusiasm for new therapeutic options. This research project will characterize patient perceptions of bioengineered probiotics and other potential clinical applications of metagenomic analyses of the human microbiome. Empirical results from the project will be presented to a Working Group of national experts in gastroenterology, biomedical ethics, health policy, and patient advocacy, who will identify opportunities to promote the responsible introduction of bioengineered probiotics into the care of patients with debilitating gastrointestinal diseases. These strategies will focus on potential health-policy initiatives and educational interventions that gastroenterologists, patient educators, and voluntary-health organizations can undertake now in anticipation of the time when bioengineered probiotic therapies may be appropriate for routine clinical use. PUBLIC HEALTH RELEVANCE: This research study will examine patient perceptions of bioengineered probiotics and other potential clinical applications of metagenomic analyses of the human microbiome. Systematic data on patient attitudes and beliefs about emerging therapeutic interventions facilitated by the Human Microbiome Project are critically important, as these data can identify potential barriers to the successful integration of bioengineered probiotics into patient care and improve physician-patient communication about new therapeutic options.

The ultimate aim of genetic research is to improve human health and prevent disease. One key measure of success in translating new genetic knowledge into improved health will be the extent to which genomic medicine reduces existing health disparities. We propose to develop a CEER on "Genetics, Vulnerable Populations and Health Disparities" dedicated to examining the complex intersection of emerging genetic research and the persistent problem of health disparities through in_depth analysis of 3 key clinical areas: tobacco dependence, asthma, and diabetes. Each of these conditions is marked by high prevalence (together, these conditions affect 85M (29 percent) of Americans), persistent health disparities (by race/ethnicity and socioeconomic status) and significant genetic findings related to disease etiology and/or response to treatment. Genomic advances in the treatment and prevention of these conditions - appropriately applied in clinical practice - would thus have far_reaching potential to improve not only our nation's health, but also to reduce existing health disparities across racial/ethnic and socioeconomic lines. Specific aims are: —> to identify and prioritize key ELSI issues related to the conduct, communication and translation of genetic research on tobacco dependence, asthma and diabetes; —> develop a research agenda to address these concerns; —> analyze high priority, policy-relevant issues (through 3 to 4 papers) to inform ongoing policy discussions and lay the groundwork for future research; —> develop the capacity to monitor the equitable diffusion of emergent genetic-based treatments across racial/ethnic communities and Medicaid vs. privately insured individuals in the U.S. through completion of a feasibility study; —> collect appropriate pilot data (e.g. focus groups, key informant interviews) to inform the P5O Center proposal; —> provide training for a minority graduate student and develop a training component to encourage new ELSI investigators from underrepresented minority communities; and —> submit a competitive P50 CEER proposal.

Research is currently underway that seeks to deepen our understanding of the role of genetic factors in substance dependence and response to treatment. In order for the potential benefits of emerging research to be realized, it is crucial to begin understanding how members of different racial/ethnic groups comprehend, interpret and respond to information about the role of genetics in addiction and treatment response, and in particular to reported racial differences in the frequency of alleles hypothesized to increase susceptibility to addiction or affect response to treatment. We use data on the genetics of nicotine addiction and response to treatment to explore these issues. Specific aims are: (1) To explore racial differences (self-identified Black versus white) in beliefs and understandings regarding the role of genetics in addiction; (2) To explore racial differences (self-identified Black vs. white) in attitudes toward the use of genetic testing to improve treatment for addiction; (3) To assess the extent to which individuals' attitudes toward the use of genetic testing in this context change when they are informed of key characteristics of the genotypes that would most likely be used to tailor individual treatment for addiction (e.g., racial differences in the frequency of risk alleles, pleiotropic associations), as reported in the most current scientific literature; (4) Among a subset of self-identified Black and white smokers in the U.S., to assess individuals' intention/willingness to undergo genetic testing in order to be matched to optimal smoking treatment. This study includes extensive qualitative research and a randomized national telephone interview survey of 1200 self-identified Black and 1200 white adults. Focus groups, personal interviews, cognitive interviews, expert review, two rounds of pre-testing, and a pilot survey (N=100) will be used to develop an effective and appropriate survey instrument. The proposed research will be the first to examine how diverse lay audiences understand, interpret and respond to emerging genetic research on addiction and potential clinical applications. Such information is essential to constructively engage the broader public in ongoing and future debates about the integration of emerging pharmacogenetic interventions into clinical practice, and to developing culturally appropriate informed consent processes, interventions and educational activities.

Emerging medical technologies are substantially improving our health care options, but often at considerable added cost. Cost-effectiveness and affordability are described as the fourth and fifth hurdles for new medical technologies, following the traditional three hurdles for licensing requirements: safety, efficacy, and quality. The Human Genome Project offers ample opportunity to improve human health through innovative genome-based technologies that have only recently become available. A number of genomic prognostic and predictive tests have been developed to assist physicians in providing better treatment for patients with early-stage breast cancer (ESBC). Clinical use of these emerging genomic tests will depend not only on the accuracy of the tests but also on their economic impacts to the society. The purpose of this study is to use methods of economic evaluation to examine the relationship between the performance of pharmacogenomic prognostic and predictive tests and their costs over a plausible range of test performance and costs for women with ESBC in the context of costeffectiveness and affordability. The specific aims are the following: —> To compare the cost-effectiveness of using pharmacogenomic prognostic tests versus current practices in the treatment of ESBC. —> To assess the cost-effectiveness of using pharmacogenomic predictive tests versus current practices in the treatment of ESBC. —> To evaluate the cost-effectiveness of using a combination of pharmacogenomic prognostic and predictive tests versus current practices in the treatment of ESBC. —> To estimate the budgetary impact of the emerging pharmacogenomic prognostic and/or predictive tests.

This qualitative, ethnographic project addresses a "Grand Challenge" for the future of genomic research and a NHGRI ELSI Research Program priority area: the analysis of the impact of genomics on concepts of race, ethnicity, and individual and group identity. The goals of the project are: (a) to describe how race and ethnicity are conceptualized by genetic epidemiologists in gene-environment interaction (GEI) studies of complex diseases; (b) to examine how those conceptions specifically and concretely impact GEI study design and actual, implemented study procedures, and (c) to analyze the consequences of the uses of race and ethnicity in GEI studies for societal understandings of race and ethnicity and individual and group differences. The controversies over the role of race and ethnicity in genomic research, documented variations in the use of race and ethnicity, and the influence that scientific findings have on societal beliefs and future research all indicate the importance of studying how genome scientists themselves conceptualize and use race and ethnicity in study design and implementation. Genetic epidemiologists conducting GEI research on the etiology of coronary heart disease (CHD), type 2 diabetes, and cancer comprise an important professional community in which to examine these questions. CHD, diabetes, and cancer are widely recognized to have genetic, behavioral, and social determinants, making a GEI approach an increasingly used modality to investigate the racial and ethnic disparities that characterize these diseases. Genetic epidemiologists frequently provide important leadership in GEI studies because of their disciplinary expertise in population-based approaches, the evaluation of multiple disease determinants, and the use of race and ethnicity. To date, no study has investigated these questions comprehensively among this professional community. Therefore, the specific aims of this study are: (1) to describe how genetic epidemiologists involved in federally-funded GEI studies of CHD, diabetes, and cancer etiology conceptualize race and ethnicity and understand their significance in GEI research; (2) to analyze how these conceptions of race and ethnicity influence the design and planned methods of GEI studies; and (3) to analyze how conceptions of race and ethnicity affect actual, implemented recruitment, data collection, analysis, and interpretation procedures, and the design of future studies. These data will be obtained from longitudinal, in-depth interviews with genetic epidemiologists, analyses of GEI study documents, and ethnographic observation of scientific conferences and ongoing GEI studies. Systematic qualitative data analysis procedures will be used to achieve the study aims. The long-term objectives of this project are: to anticipate and analyze how conceptions of race and ethnicity used in GEI research influence societal understandings of race, ethnicity, and individual and group identity; and to identify how policies and practices regarding the conceptualization, measurement, and interpretation of race and ethnicity in genomic research might be elaborated in ways that render them more meaningful or robust. PUBLIC HEALTH RELEVANCE: This project will yield new knowledge useful for improving the conceptualization of and methodological practices associated with race and ethnicity, particularly in the context of GEI research, a major emerging trend in genome science. Findings from this project can help inform how practices regarding the measurement and use of race and ethnicity might be standardized in ways that make them more meaningful and robust, and under what kinds of conditions genome scientists might find such standardization less than useful. This project will therefore provide important information both for considering the ethical and societal impact of genomic research on concepts of individual and group identity, and of race and ethnicity, and for shaping future measures and methods used in genomic and gene-environment interaction research on health disparities.

Targeted gene sequencing using large panels has become an increasingly important strategy for evaluating disease risk for many inherited diseases. Expanded gene panels are more sensitive than single gene testing and often more cost effective than sequential testing, leading to additional diagnostic and prevention opportunities. However, these panels also identify rare variants of uncertain clinical significance (VUS) in many patients. VUS typically have some characteristics or associated data indicating the variant may be deleterious, but not enough information to definitively classify them as disease causing. It is estimated that hundreds of thousands of such variants are present at low frequencies in the population. The finding of a VUS is problematic for patients and clinicians. Family segregation studies have the potential to yield powerful data to classify variants, but research resources are inadequate to enroll all the families affected by the exploding number of VUS identified in clinical testing. A potential solution to this quandary is to engage patients and their families in performing meaningful segregation analysis to evaluate their own VUS using available online genealogy and social networking tools facilitate identifying and contacting relatives likely to have the same VUS. In this project we will interview patients who have received clinical reports of VUS to explore patient understanding of their VUS, motivation and interest in classification, opinions of barriers and facilitators to talking with family members about VUS, and initial thoughts about potential for providing samples to classify their VUS. We will use input from 15-25 study participants to evaluate and improve an online patient-driven VUS classification toolkit that teaches individuals to better understand their VUS, use available genealogy and networking resources trace how their own variants segregate in their extended family, and potentially participate meaningfully with clinical experts in the classification of their own VUS. We will work with participants to obtain and test DNA from family members, and a molecular genetic pathologist will perform final variant classification. We will interview participants to determine if goals were met and if the toolkit enhanced participant and family understanding of genetic disease risk. We will also interview family members to understand family members perspectives related to privacy, communication, and provision of data or samples for variant classification. The innovative tools to classify VUS that will be developed in this project will meet a growing clinical need. When made broadly available these tools may demonstrate a way to characterize human variants in clinical settings at an unprecedented pace and at a fraction of the current research cost. The data gathered from this initial R21 project will lay the groundwork for additional development of a systematic, family-based method to help patients understand and classify variants of uncertain significance.

This project will continue and expand the Prospective Huntington At Risk Observational Study (PHAROS). PHAROS is a collaborative effort involving 43 recruitment and evaluation centers in the US and Canada. Its goal is to recruit 1000 individuals who are at 50% risk to develop Huntington disease (HD). These are all individuals who have not undergone, nor do they plan to undergo genetic testing in which they will learn their test results. The three major goals of this research are to: define the earliest clinical precursors of HD; identify other genetic and environmental modifiers of HD onset; and collect information about beliefs and attitudes of participants who know they are at risk to develop HD, but choose not to undergo genetic testing.

The purpose of this project is to develop, implement and evaluate a model comprehensive genetic education program for health, education and human services professionals in Mississippi. The project will also facilitate the dissemination of this program (GenESES) into continuing education programs of southeastern states and into pre-service training programs of institutions of higher learning. The specific objectives of these project are: —> to develop appropriate curriculum materials for GenESES that are responsive to the needs and relevant to the experiences of health, education, and human services professionals through integration of an interdisciplinary, family-centered, and community-based approach; —> to test, evaluate and modify the pilot GenESES curriculum through implementation of nine workshops with participants representing multidisciplinary health, human services, and education professionals; —> to evaluate the impact of the GenESES Project on the knowledge base and clinical practice of participating professionals; and —> to facilitate dissemination of the GenESES Project into continuing education programs of southeastern states and into pre-service training programs of institutions of higher learning.

The long-term goal of this research is to develop multimedia technology and interactive instructional strategies to improve the effectiveness and efficiency of obtaining informed consent for human DNA and tissue biorepositories. Studies suggest that individuals do not sufficiently understand the information presented during biorepository consent processes, and that traditional consent processes pose resource challenges for large-scale biorepositories. Based on experiments testing multimedia presentations for patient education purposes, multimedia has the potential to improve the effectiveness and efficiency of obtaining biorepository informed consent by increasing participant understanding and recollection of information presented. Yet, this potential has not been systematically investigated in the unique context of biorepository consent. In particular, there is a need to understand the separate effects of interactivity (i.e., question asking, feedbac provided to subjects) and multimedia (i.e., multiple information delivery formats) on participant knowledge, understanding, and decision to participate. This study will compare a standard paper-based consent process (control) to multimedia and interactive consent processes, using an experimental design with random assignment, integrated into actual recruitment at the University of Iowa Hospitals and Clinics' (UIHC) comprehensive DNA and tissue biorepository. To assess the separate effects of interactivity and multimedia, low and high interactivity conditions will be tested for both the paper and the multimedia conditions. In the high interactivity conditions, participants will be asked questions about the information presented and provided feedback on their responses. Interactivity and multimedia are expected to significantly improve subject knowledge and understanding when compared to the paper-based control. High interactive multimedia is expected to decrease staff time devoted to obtaining informed consent. Two hundred (200) patients will participate in the study from the Dermatology and Immunology/Rheumatology Clinics at the UIHC. Participants will be enrolled into the UIHC biorepository via one of the four study conditions. Results of the study will be used to develop a multisite comparative study designed to demonstrate the effectiveness and efficiency of interactivity and multimedia consent under different environments, forms of media, and informed consent protocols. This research has the potential to improve on current paper-based informed consent processes and to establish the feasibility of alternative, and more effective, multimedia consent processes for human DNA and tissue biorepositories and other research-driven efforts in genetics and genomics. PUBLIC HEALTH RELEVANCE: Biorepositories may ask thousands of people a year to donate biological samples, allow access to their health information, and participate in research. Yet, there is little research on the best ways to deliver informed consent information to individuals so that they can make an informed decision about participating in biorepositories. This study will test an interactive, multimedia tool for delivering informed consent information about biorepositories to individuals in an understandable and effective way.

Interactive Multimedia Consent for Biobanking Abstract Many biobanks in the U.S. consent thousands of contributors of biospecimens and health information. There is growing interest in the efficiency of electronic consenting (e-consent) given the scale of these efforts. However, e-consent tools also need to promote diverse users' understanding and trust, and demonstrate their effectiveness in comparison to traditional methods such as face-to-face (F2F) consenting. For e-consent to be successful, biobanks require well-designed e-consent tools that meet diverse user needs and preferences. Thus, empirical research on the design and effectiveness of e-consent is critical for biobank stakeholders to determine whether and how to implement e-consent processes. The long-term objective of this three-year (R01) study is to improve the efficiency and effectiveness of informed consent through use of systematically developed e-consent tools. The immediate objective is to develop and test an interactive, multimedia (IM) e- consent tool based on theories of cognition and learning, resulting in guidelines for biobanks to develop their own e-consent processes. The specific aims of the study are to systematically (1) refine and evaluate a model process for developing IM e-consent tools for biobanking and (2) compare the effectiveness and efficiency of IM to standard F2F consent processes for biobanking. For Aim 1, a prototype IM consent module, including a Spanish language version, will be developed with iterative feedback from biobank staff, IRBs, IT experts, and prospective users at three genetic biobank operations in the East, South, and Midwest. Focus groups and interviews will be conducted with stakeholders at each biobank, to generate insights into the utility of stakeholder engagement in the module development process. This aim of the study will generate essential guidance for biobanks and other research entities wanting to transition to e-consent. It will also provide three IM modules with which the study's partner biobanks can begin consenting electronically. In Aim 2, a multisite randomized trial will be conducted with a total of 700 participants at the study's three partnering biobanks, including one site with a simplified (2-page) consent document and Spanish-language version. The trial will test the hypotheses that 1) individuals who use the IM multimedia consent tool will have better understanding and confidence in their understanding, higher trust in biobank research and higher satisfaction compared to individuals who complete the biobanks' standard, F2F consents, when controlling for age, gender, race/ethnicity, education, computer self-efficacy and income; and 2) staff will spend less time in the IM consent process, compared to time spent in the biobanks' standard, F2F consents. Significant numbers of traditionally underrepresented minorities will be enrolled in the trial. This aim of the study wll provide empirical evidence for IRBs and the broader genomic research community to decide whether to move forward with electronic, IM consenting. Overall, the study is expected to contribute to ethical, cost-effective consenting efforts through in- depth empirical knowledge of IM e-consent technology.

Various theories have been offered about the significance of attributing behavioral characteristics - for example, propensity to violence, intelligence, alcoholism, and obesity to genes or genetic inheritance. On the one hand, genetic explanations may absolve people from blame for characteristics considered socially undesirable; on the other hand, belief in genetic determinism may signify that these undesirable characteristics are unchangeable, and that efforts to improve the environment for example, to improve educational opportunities for Blacks and women are futile and unnecessary. Such beliefs about the role of genes are especially significant if they are used to justify discrimination or prejudice toward minority groups. Work by Jayaratne and her colleagues (forthcoming), as well as others suggests that the attribution of individual and group differences to genetic causes is greater among Whites than among Blacks, and is linked to prejudiced attitudes toward minority groups. Singer and Antonucci (unpublished) found a similarly greater tendency for Whites to attribute behavior to genes even when the question involved abstract characteristics rather than differences between groups. Our current work, on the other hand (Singer et al., in progress), finds a consistent tendency for Black raters as well as less educated raters to make more genetic attributions than White raters or better educated raters. Both race and education make an independent contribution to the rating of the behavioral characteristics. We believe that these and other differences in findings can be accounted for, in large part, by differences in the way questions have been asked; in other words, to differences in framing (CITES). The present proposal aims to test the hypothesis of framing effects empirically, using a factorial experimental design administered on the Web. Differences in framing of the survey questions are important because they are likely to reflect similar differences in the public discourse on the issue, which in turn affects public attitudes and government policies.

New developments in biotechnology, such as the ability to identify the genetic basis of many single gene disorders, and the progress in identifying the genetic basis for more complex disorders have the potential for bringing about dramatic social changes. The present study, funded by NSF in 1988, is designed to trace the evolution of one set of such changes, namely, changes in attitudes and values related to the ability to diagnose genetic disorders without being able to cure them. It analyzes three interrelated developments: reporting about genetic screening and related issues in the mass media; positions toward genetic screening taken by a variety of interest groups; and public knowledge, attitudes, and values related to prenatal genetic testing and genetic screening in the workplace, as measured by interviews with a national sample of adults.

The aim of this proposal is to add to the limited store of knowledge available about public values and attitudes relevant to various aspects of genetic technology. The proposal has two specific aims. The major aim is to investigate experimentally the determinants of people's beliefs about the relative contribution of heredity and environment to differences in such behavioral characteristics as aggression, shyness, and alcoholism. A second aim of the proposal is to investigate trends in knowledge about and attitudes toward genetic testing and genetic technology by replicating questions previously asked in two earlier studies. Given the rapid changes and developments in the field of genetics, and their increasing availability to the public via the mass media, we expect to see changes in attitudes as well. The vehicle for the study will be the 2004 General Social Survey (GSS), a national face-to-face survey of the adult household population of the U.S. The proposed study of beliefs about genetic and environmental influences on behavior will systematically vary (a) the social desirability of the condition or characteristic asked about as well as (b) the race/ethnicity and (c) the gender of the person manifesting the characteristic in order to determine how each of these affects the judgments made. In addition, we will assess the significance for such judgments of the rater's own sociodemographic characteristics (e.g. race, ethnicity, age, education, marital status, and religion), as well as such aspects of the rater's personality as locus of control, optimism-pessimism, and the need for self-esteem. By including four questions about genetic testing among those we add to the survey, we will be able to investigate beliefs about genetic and environmental influences on behavior.

The overall aim of this ethnographic and longitudinal project is to assess how parents from different cultural backgrounds who have a child or who are at risk for having a child with a genetic disorder seek out, understand, and use knowledge (including information received during genetic counseling and evaluation) to interpret genetic disorders and their experiences, and to make decisions about reproduction, health, and services. A collaborative team of genetic, social science, and education researchers will employ systematic interview and observation methods to study 130 families who are referred to a medical genetics counseling program for counseling and/or evaluation. One hundred families (40 African American, 40 European American, 10 Latino, and 10 Native American) who attend and 30 families (10 African American, 10 European American, 5 Latino, and 5 Native American) who choose not to attend will be followed over a two year period. Employing systematic analyses based on anthropological theories and methods, investigators will examine data from detailed observations of the clinical genetics visit and a series of semi-structured, face-to-face interviews with parents to provide a comprehensive view of —> how parents understand and are directed by information disseminated during the clinical session; —> what other sources of information and beliefs (e.g., biomedical, popular or ethnocultural models of the gene and inheritance; religious beliefs) parents draw on to make sense of disability and genetic disorder; —> the process of how they piece together various knowledges and beliefs; —> and how they make decisions for themselves and their child based on their interpretations and experience. Analysis will also focus on the differences in these outcomes based on family and child characteristics.

This project will develop ethical guidance for presymptomatic testing for autosomal dominant, late onset diseases for which genetic probes are available (familial Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, myotonic dystrophy, neurofibromatosis, adult polycystic kidney disease and retinitis pigmentosa). Our six-member working group offers expertise in genetic counseling, clinical medical ethics, genetic research, law, ethics and communication. We will collect and analyze case studies, beginning with Indiana University's extensive experience with Huntington disease (HD). We will define the full range of ethical problems presented by presymptomatic testing for these disorders, and we will explore the salient questions from the varied perspectives represented by the working group, considering ethical principles (autonomy, beneficence, justice); clinical practicality; administrative feasibility; changing research findings; religious beliefs and institutions; and political, cultural and economic contexts. In addition, we will solicit input from genetic counselors and others experienced with presymptomatic testing, and we will invite patients and families at risk to review our materials in progress to assess their sensitivity, adequacy and feasibility. Our final product, a book published by Indiana University Press, will include guidelines for presymptomatic testing of autosomal dominant, late onset disorders; annotated cases; and the description of a method for resolving ethical issues our guidelines do not address directly.

This conference, which will take place over a three-day period at the Kellogg Executive Conference Center at Tuskegee University in September 1996, will provide a forum for increasing awareness of the Human Genome Project (HGP) in a segment of the African-American (AA) community, particularly those associated with Historically Black Colleges and Universities (HBCU). The conference, and the workshops to follow, will emphasize technological, social and ethical issues arising from the HGP. Technical and education concerns to be addressed include the need for incorporation of genome analysis in the HBCUs school curricula, and increasing internship opportunities for AA students at Genome Centers. Sociological and ethical concerns on the use of data from HGP will also be discussed. Participants to be invited to the Tuskegee Genome Conference include scholars, educators, researchers, community leaders and consumers of genetic information from the HGP. As a result of this conference, participating HBCU institutions will have an opportunity to develop an enhanced level of participation and awareness of the conduct of on-going genome research programs. In addition, it will increase awareness in the African American community of the legal and ethical issues surrounding genetic research and screening.

Genomic medicine has, on one hand, the power to predict potentially debilitating disease before its actual onset; on the other hand, it creates challenges for patients in determining how to assess uncertainty and the risk of developing genomic-related adult-onset medical conditions. If adults are married when genetic testing occurs, they may discuss the test results with their spouses and decide on future actions together, such as disclosing the genetic test results to others; their spouses may also be affected by these discussions and decisions. This project, then, provides insights into the social implications of genetic tests. Current research on spousal discussions of genetic tests focuses on asymptomatic adults considering risks of future conditions for themselves or genetic implications for their children. In this era of personalized medicine, genetic tests are increasingy included with traditional diagnostics. For example, when adults present with symptoms such as shortness of breath or wheezing, diagnostic efforts may include screening for chronic infections, along with evaluation of patient genotype to establish risk for Alpha-1 antitrypsin deficiency (AATD). AATD fits into a class of genetic conditions in which clinical onset is in adulthood, likelihood of development is variable, and treatment and/or lifestyle modification can alter the onset or progression of clinical conditions. Other conditions fitting into this category are BRCA 1/2 mutations associated with breast cancers. Adults managing serious chronic illnesses may discover they have a genetic risk for their AOMC. By focusing on couples' communication about AATD test results, we can reveal illness and relational challenges faced by couples and how symptomatic and asymptomatic scenarios may influence management in both realms. In this project, we test a theoretical model for genomic/genetic medical decision-making (GMD) that formalizes how spouses' beliefs about genetics predict (a) their within-couple communication about the genetic information, (b) what information they share and with whom, and (c) patients' and spouses' overall wellbeing and protective behaviors. To date, the interdependence in couples' beliefs and within-couple influences in GMD has been unexamined. By gathering information from both spouses, we can identify intrapersonal, interpersonal, and couple-level influences in GMD. Persons diagnosed with AATD and their spouses have been surveyed in collaboration with the Alpha-1 Research Registry. The proposed work will use quantitative techniques to analyze how well the proposed GMD model fits these data, in order to identify sub-groups of couples based on their genetic beliefs, conversation patterns, and wellbeing. The theory and sub-group findings will be used to develop targeted materials with support agencies to support couples managing genetic test results. A future R01 project will test these targeted materials through website deployment, including a pre-exposure, online quiz for couples so they can access relevant materials for them. PUBLIC HEALTH RELEVANCE: This project will analyze survey responses from Alpha-1 Research Registry members and their spouses to uncover social influences in genetic/genomic medical decision-making. The results will uncover how couples process genetic test results to identify unintended consequences for their relationship and their wellbeing.

Harvesting the benefits of genomics requires a new kind of transdisciplinary cooperation. Over the next three years, we will create the Center for Transdisciplinary ELSI Research in Translational Genomics (CT2G) to address key ELSI questions in translational research. The proposed Center brings together the unique resources of Kaiser Permanente Northern California (KPNC), including its Division of Research, and the University of California, San Francisco (UCSF), including the Hastings College of the Law Consortium on Law, Science & Health Policy. A key CT2G resource for training, research, deliberation, and policy analysis is the Kaiser Permanente "Research Program on Genes, Environment, and Health" (RPGEH), designed to foster epidemiological studies. The RPGEH links together participants' data from electronic medical records, biospecimens, health surveys and geographic information systems. The RPGEH includes genome-wide genetic data and measures of telomere length from a sample of over 110,000 men and women, who constitute the Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort. Deepening the existing collaborations between scientists and clinicians at KPNC and UCSF, and utilizing the unique structure of KPNC's integrated health care delivery system, we aim to: 1) Create CT2G and nurture its development as a novel resource for ELSl research in translational genomics. * Implement a management plan and form a Steering Committee and External Advisory Panel * Develop a strong intellectual community through a website, seminar series, and annual conferences * Fund small pilot projects to elucidate barriers to effective genomics translation 2) Convene joint KPNC/UCSF working groups to address critical issues in translational genomics. Focusing on projects with tangible outcomes, we will bring together scholars who have not yet collaborated, creating a blueprint for long-term transdisciplinary work that joins empirical and normative approaches. 3) Plan and initiate a program in ELSI education focused on pre-doctoral students and clinicians. * To expand the pool of under-represented minority ELSI scholars, we will plan and gain approval for a pre-doctoral fellowship program for students from a range of disciplines. * To enhance transdisciplinary collaboration, we will develop a one year ELSI fellowship for clinicians from multiple fields, including nursing, pharmacy, genetic counseling, and clinical medicine. PUBLIC HEALTH RELEVANCE: To facilitate the translation of genetic discoveries into improvements in prevention, clinical care, and public health, we will create a Center to encourage collaboration among scholars from many fields, and to train clinicians. The CT2G will develop better ways to protect research subjects and create strategies for inclusion of public voices in the management of genomic data. Our goal is to ensure that society benefits from genomic discoveries in a manner that diminishes, rather than exacerbates, health disparities.