Oral microbiome diversity among Cheyenne and Arapaho individuals from Oklahoma.

OBJECTIVES: There is a major ascertainment bias in microbiome research, with individuals of predominately European ancestry living within metropolitan areas dominating most studies. Here we present a study of the salivary microbiome within a North American Indian community. This research is the culmination of four years of collaboration and community engagement with Cheyenne & Arapaho (C&A) tribal members from western Oklahoma. MATERIALS AND METHODS: Using 16S rRNA gene amplification and next-generation sequencing, we generated microbial taxonomic inventories for 37 individuals representing five towns within the C&A tribes. For comparison, we performed the same laboratory techniques on saliva samples from 20 non-native individuals (NNI) from Norman, Oklahoma. RESULTS: The C&A participants differ from the NNI in having reduced within-individual species richness and higher between-individual variation. Unsupervised clustering analyses reveal that three ecological groupings best fit the data, and while C&A individuals include assignments to all three groups, the NNI individuals are assigned to only one group. One of the ecological groups found exclusively among C&A participants was characterized by high abundance of the oral bacterial genus Prevotella. DISCUSSION: The C&A and NNI participants from Oklahoma have notable differences in their microbiome diversity, with a wider range of variation observed among the C&A individuals, including a higher frequency of bacteria implicated in systemic disorders. Overall, this study highlights the importance of engagement with indigenous communities, and the need for an improved understanding of human microbiome diversity among underrepresented groups and those individuals living outside of metropolitan areas.

Regional differences in awareness and attitudes regarding genetic testing for disease risk and ancestry.

Little is known about the lay public's awareness and attitudes concerning genetic testing and what factors influence their perspectives. The existing literature focuses mainly on ethnic and socioeconomic differences; however, here we focus on how awareness and attitudes regarding genetic testing differ by geographical regions in the US. We compared awareness and attitudes concerning genetic testing for disease risk and ancestry among 452 adults (41% Black and 67% female) in four major US cities, Norman, OK; Cincinnati, OH; Harlem, NY; and Washington, DC; prior to their participation in genetic ancestry testing. The OK participants reported more detail about their personal ancestries (p = 0.02) and valued ancestry testing over disease testing more than all other sites (p < 0.01). The NY participants were more likely than other sites to seek genetic testing for disease (p = 0.01) and to see benefit in finding out more about one's ancestry (p = 0.02), while the DC participants reported reading and hearing more about genetic testing for African ancestry than all other sites (p < 0.01). These site differences were not better accounted for by sex, age, education, self-reported ethnicity, religion, or previous experience with genetic testing/counseling. Regional differences in awareness and attitudes transcend traditional demographic predictors, such as ethnicity, age and education. Local sociocultural factors, more than ethnicity and socioeconomic status, may influence the public's awareness and belief systems, particularly with respect to genetics.

Looking for race in all the wrong places: analyzing the lack of productivity in the ongoing debate about race and genetics.

The ongoing debate about the relationship between race and genetics is more than a century old and has yet to be resolved. Recent emphasis on population-based patterns in human genetic variation and the implications of those for disease susceptibility and drug response have revitalized that long-standing debate. Both sides in the debate use the same rhetorical device of treating geographic, ancestral, population-specific, and other categories as surrogates for race, but otherwise share no evidentiary standards, analytic frameworks, or scientific goals that might resolve the debate and result in some productive outcome. Setting a common goal of weighing the scientific benefits of using racial and other social heuristics with testable estimates of the potential social harms of racialization can reduce both the unreflexive use of race and other social identities in biological analyses as well as the unreflexive use of racialization in social critiques of genetics. Treating social identities used in genetic studies as objects for investigation rather than artifacts of participant self-report or researcher attribution also will reduce the extent to which genetic studies that report social identities imply that membership in social categories can be defined or predicted using genetic features.

Evaluating the utility of personal genomic information.

In evaluating the utility of human genome-wide assays, the answer will differ depending on why the question is asked. For purposes of regulating medical tests, a restrictive sense of clinical utility is used, although it may be possible to have clinical utility without changing patient's outcomes and clinical utility may vary between patients. For purposes of using limited third party or public health resources, cost effectiveness should be evaluated in a societal rather than individual context. However, for other health uses of genomic information a broader sense of overall utility should be used. Behavioral changes and increased individual awareness of health-related choices are relevant metrics for evaluating the personal utility of genomic information, even when traditional clinical benefits are not manifested. In taking account of personal utility, cost effectiveness may be calculated on an individual and societal basis. Overall measures of utility (including both restrictive clinical measures and measures of personal utility) may vary significantly between individuals depending on potential changes in lifestyle, health awareness and behaviors, family dynamics, and personal choice and interest as well as the psychological effects of disease risk perception. That interindividual variation suggests that a more expansive overall measure of utility could be used to identify individuals who are more likely to benefit from personal genomic information as well as those for whom the risks of personal information may be greater than any benefits.

Genes, Race, and Causation: US Public Perspectives About Racial Difference.

Concerns have been raised that the increase in popular interest in genetics may herald a new era within which racial inequities are seen as 'natural' or immutable. In the following study, we provide data from a nationally representative survey on how the US population perceives general ability, athleticism, and intellect being determined by race and/or genetics and whether they believe racial health inequities to be primarily the product of genetic or social factors. We find that self-described race is of primary importance in attributing general ability to race, increasing age is a significant factor in attributing athleticism and intellect to genes and race, and education is a significant factor in decreasing such racially and genetically deterministic views . Beliefs about the meaning of race are statistically significantly associated with respect to the perception of athletic abilities and marginally associated with the perception of racial health inequalities being either socially or genetically derived. Race, education, socioeconomic status, and concepts of race were frequently found to be multiplicative in their statistical effects. The persistent acceptance of a genetically and racially deterministic view of athleticism among the White and older population group is discussed in respect to its social impact, as is the high level of agreement that general abilities are determined by race among non-White respondents and those of lower socioeconomic status. We argue that these findings highlight that both biological and non-biological forms of understanding race continue to play a role into the politics of race and social difference within contemporary US society.

Barriers and Strategies Related to Qualitative Research on Genetic Ancestry Testing in Indigenous Communities.

Conducting genetics-related research with populations that have historically experienced considerable harm and little benefit from genetics research poses unique challenges for understanding community-based perceptions of new genetic technologies. This article identifies challenges and strategies for collecting qualitative data on the perceptions of direct-to-consumer (DTC) Genetic Ancestry tests (GAT) among diverse Indigenous communities. Based on a 3-year project related to perceptions, attitudes, and values associated with genetic ancestry testing among diverse Indigenous communities in Oklahoma, the engagement process revealed specific opportunities to improve the process of qualitative data collection related to GAT, and more broadly, to conduct genetics-related research with Indigenous communities in culturally and methodologically appropriate ways. Priority areas include issues related to participant recruitment and tribal advisory boards, challenges of self-identification as a recruitment mechanism, and the necessity of including Indigenous researchers in all aspects of the research process.

Investments in cancer genomics: who benefits and who decides.

The Cancer Genome Atlas--formerly the Human Cancer Genome Project--provides an opportunity for considering how social concerns about resource allocation are interrelated with practical decisions about specific research strategies--part of a continuing convergence between scientific and public evaluations of priorities for biomedical research funding. For example, the manner, order, and extent that The Cancer Genome Atlas selects tumor types and populations to be sampled will determine who benefits most from its findings. Those choices will be determined on the basis of both scientific and social values. By soliciting public involvement and conducting rigorous policy analysis in the design of large scientific projects such as The Cancer Genome Atlas, cancer researchers can help democratize the allocation of scientific resources and foster public confidence in biomedical research.

Analyzing the use of race and ethnicity in biomedical research from a local community perspective.

Lost in the debate over the use of racial and ethnic categories in biomedical research is community-level analysis of how these categories function and influence health. Such analysis offers a powerful critique of national and transnational categories usually used in biomedical research such as "African-American" and "Native American." Ethnographic research on local African-American and Native American communities in Oklahoma shows the importance of community-level analysis. Local ("intra-community") health practices tend to be shared by members of an everyday interactional community without regard to racial or ethnic identity. Externally created ("extra-community") practices tend to be based on the existence of externally-imposed racial or ethnic identities, but African-American and Native American community members show similar patterns in their use of extra-community practices. Thus, membership in an interactional community seems more important than externally-imposed racial or ethnic identity in determining local health practices, while class may be as or more important in accounting for extra-community practices.

Will investments in large-scale prospective cohorts and biobanks limit our ability to discover weaker, less common genetic and environmental contributors to complex diseases?

Increasing the size of prospective cohorts and biobanks is one approach to discovering previously unknown contributors to complex diseases, but it may come at the price of concealing contributors that are less common across all the participants in those larger studies and of limiting hypothesis generation. Prospective cohorts and biobanks constitute significant, long-term investments in research infrastructure that will have ongoing consequences for opportunities in biomedical research for the foreseeable future. Thus, it is important to think about how these major additions to research infrastructure can be designed to be more productive in generating hypotheses for novel environmental contributors to complex diseases and to help identify genetic and environmental contributors that may not be common across the larger samples but are more frequent within local or ancestral subsets. Incorporating open-ended inquiries and qualitative information about local communal and ecologic contexts and the political, economic, and other social structures that affect health status and outcome will enable qualitative hypothesis generation in those localized contexts, as well as the collection of more detailed genealogic and family health history information that may be useful in designing future studies. Using communities as building blocks for larger cohorts and biobanks presents some practical and ethical challenges but also enhances opportunities for interdisciplinary, multilevel investigations of the multifactorial contributors to complex diseases.

Community involvement in the ethical review of genetic research: lessons from American Indian and Alaska Native populations.

The National Bioethics Advisory Commission has proposed that regulatory oversight for research with human subjects be extended beyond the protection of individual research participants to include the protection of social groups. To accomplish this, the commission recommends that investigators and ethics review boards a) work directly with community representatives to develop study methods that minimize potential group harms, b) discuss group implications as part of the informed consent process, and c) consider group harms in reporting research results. We examine the utility of these recommendations in the context of research with American Indian and Alaska Native communities. Because much attention has been given to the question of how best to consult with members of these communities in the design and conduct of research, we believe it behooves investigators to consider the lessons to be learned from research involving American Indians and Alaska Natives. After describing several difficulties surrounding the application of the commission's approach to these research contexts, we propose a research agenda to develop best practices for working with local communities in the ethical assessment of epidemiologic and environmental health research.

A practice approach for identifying previously unsuspected environmental contributors to systemic lupus erythematosus and other complex diseases.

Existing medical records and health surveys provide insights into potential environmental contributors to complex chronic diseases. Those recognizable risks (e.g., workplace exposures and behaviors including smoking) do not, however, exhaust the domain of potential environmental contributors. Qualitative ethnographic investigation can be used to generate statistically testable hypotheses about environmental contributors to complex disease that otherwise would not be recognized as such. Consequently, we can empirically specify lifestyle beliefs and behaviors usually summarized by proxy identities such as race, ethnicity, gender, class, and culture. The investigation of potential environmental contributors to complex diseases may be particularly useful in confirming or disconfirming suggestive or established linkages and for indicating the kind of gene-environment interaction that may be involved.

The Human Microbiome Project: lessons from human genomics.

The Human Microbiome Project (HMP) is following in the footsteps of the Human Genome Project (HGP), which will include exciting discoveries, but also potential disappointment and resentment over the lack of medical applications. There is a wiser path for the HMP. This path includes a greater attention to rare variation, an early commitment to an ethical inclusion of indigenous communities, and a recruitment strategy in which medical benefits are de-emphasized.

The contractual genome: how direct-to-consumer genomic services may help patients take ownership of their DNA.

The sequencing and genotyping of personal genomes by commercial services outside traditional clinical settings may help to shape the expectations of research subjects and patients regarding control of and responsibility for the information contained in their DNA. A greater sense of individual ownership of personal genomic information could replace overly complex and paternalistic institutional proxies for the protection of personal genotype and sequence data, and also could encourage research participants and patients to become better educated regarding genetic contributors to disease.

Estimation of the prevalence of AIDS, opportunistic infections, and standard of care among patients with HIV/AIDS receiving care along the U.S.-Mexico border through the Special Projects of National Significance: a cross-sectional study.

There is high demand for care among the Hispanic population in states along the U.S.-Mexico border. The objective is to describe the standard of care received by people living with HIV/AIDS (PLWH/A) at enrollment into one of five Special Projects of National Significance (SPNS) Sites located along the U.S.-Mexico border. This cross-sectional study describes the presence of opportunistic infections (OIs), AIDS status and two types of standard of care received by 707 PLWH/A participating in SPNS. Patients receiving care through SPNS in one of the five sites between June 1, 2002 and December 31, 2003 were invited to participate to the medical chart review component of the study. The association between sociodemographic variables and the prevalence of OIs and AIDS at enrollment was estimated using multivariate hierarchical logistic models. More than one quarter of the 707 participants had at least one OI recorded and 58% of new and 60% of existing patients had AIDS at enrollment in SPNS. The association between being Hispanic and having higher prevalence of OI and AIDS at entry varied by SPNS site. Standard of care was well followed overall. This is the first study describing HIV stage and OI prevalences and standard of care in PLWH/A in all U.S.-Mexico bordering states. Being of Hispanic ethnicity may not fully explain discrepancy in access to care along the border.

Share and share alike: deciding how to distribute the scientific and social benefits of genomic data.

Emerging technologies make genomic analyses more efficient and less expensive, enabling genome-wide association and gene-environment interaction studies. In anticipation of their results, funding agencies such as the US National Institutes of Health and the Wellcome Trust are formulating guidelines for sharing the large amounts of genomic data that are generated by the projects that they sponsor. Data-sharing policies can have varying implications for how disease susceptibility and drug-response research will be pursued by the scientific community, and for who will benefit from the resulting medical discoveries. We suggest that the complex interplay of stakeholders and their interests, rather than single-issue and single-stakeholder perspectives, should be considered when deciding genomic data-sharing policies.

Grappling with groups: protecting collective interests in biomedical research.

Strategies for protecting historically disadvantaged groups have been extensively debated in the context of genetic variation research, making this a useful starting point in examining the protection of social groups from harm resulting from biomedical research. We analyze research practices developed in response to concerns about the involvement of indigenous communities in studies of genetic variation and consider their potential application in other contexts. We highlight several conceptual ambiguities and practical challenges associated with the protection of group interests and argue that protectionist strategies developed in the context of genetic research will not be easily adapted to other types of research in which social groups are placed at risk. We suggest that it is this set of conceptual and practical issues that philosophers, ethicists, and others should focus on in their efforts to protect identifiable social groups from harm resulting from biomedical research.

Ethical issues in medical-sequencing research: implications of genotype-phenotype studies for individuals and populations.

Advances and declining costs in sequencing technology will result in increasing number of studies with individual sequence data linked to phenotypic information, which has been dubbed medical sequencing. At least some of this linked information will be publicly available. Medical sequencing raises ethical issues for both individuals and populations, including data release and identifiability, adequacy of consent, reporting research results, stereotyping and stigmatization, inclusion and differential benefit and culturally and community-specific concerns. Those issues are reviewed, along with possible solutions to them.