Race and ancestry in biomedical research: exploring the challenges

Recent advances in biomedical research promise increasing insights into complex contributions to traits and diseases, and there is hope that these will lead to global health benefits [1, 2]. Analytical and social-justice considerations both recommend thoughtful assessment of the role of social identity, particularly racial or ethnic identity, in the design, conduct and dissemination of clinical and basic science research. Controversies ranging from James Watson's comments on racial differences in intelligence [3] to the adoption of racially targeted pharmaceuticals, such as the African-American heart-failure drug BiDil [4–7], remind us that use of the concept of race in biomedical research can have far-reaching, often unanticipated social consequences.

The problem of race in scientific research is not a new one, and the issue seems to perpetually reappear and remain fundamentally unresolved [8]. We are, however, entering a new era in which the fruits of initiatives, such as the Human Genome Project [9, 10], the International Haplotype Map Project [11], and the recently proposed 1000 Genomes Project [12], promise to elaborate more fully than ever before the nature and extent of human genetic variation and its relation to social identity. A recent interdisciplinary workshop, 'Ancestry in health and medicine; expanding the debate', hosted by the Alberta Health Law Institute and the McLaughlin-Rotman Centre for Global Health, in Toronto, Canada, sought to debate the current status and concerns surrounding these new scientific data, how we relate genetic variation to individual and population-level differences in observable traits, and what this might mean for the effective addressing of significant disparities in health status and disease. A central motivating consideration was how best to secure the anticipated benefits of genetic and related forms of biomedical research in the face of inevitable misunderstandings or misuse concerning genetic variation and race.

Here, we draw together the perspectives of the scholars who participated in the workshop, who have considered the race issue from the vantage point of a variety of disciplines: anthropology, bioethics, clinical medicine, ethical, social, cultural studies, genetic epidemiology, genome sciences, global heath research, law and the social sciences. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action.

At the heart of ongoing debates about the value and use of racial categories in biomedical research are disagreements about the underlying rationale (and motivation) for stratifying study cohorts and what to do with resulting observations. Although there is considerable interest in using social or political categories in the descriptive assessment of health outcome similarities and differences, several scholars have suggested that the subsequent attribution of causality to those categories is unjustified and potentially harmful [13, 14]. So, although there is much agreement that race (and other forms of social identification) matters to health, there is little agreement about why or how race matters, how best to study its effects and how to translate and communicate research results from racially stratified studies (see Box 1).

Persistent disagreements about how best to understand race as an object of scientific inquiry complicate matters further. Racial definitions can fluctuate according to social context, geographic location, historical period and personal experience. Indeed, it is not uncommon for the same individual to report their racial identity differently in different contexts and at different points in their lives [15–17]. For these and related reasons many scholars view racial identity as primarily a social construct [18–22], and one that can misdirect the categorization of participants in biomedical research. Others see racial identity as correlated with a mix of social and biological risk factors that should be recognized and disentangled, even used to advantage, in an effort to explain and address health disparities [23–26].

Despite research correlating population genetic identity with geographic proximity [27–30], many researchers hold that self-identified racial or ethnic identity is a poor proxy for underlying genetic relatedness [31–34]. As a consequence, scientists with an interest in identifying genetic-association studies with disease are turning to DNA-based estimates of 'ancestry' as a basis for stratifying study samples and controlling for background genetic differences unrelated to disease risk [35–37]. Geneticists have also begun to use ancestry informative markers (AIMs) to identify groups and individuals subject to recent genetic admixture and use this information in methods such as admixture mapping [38–40]. In both gene-association and admixture studies, assessing ancestry is seen as preferable because it circumvents the problems of self-reporting, although major axes of differentiation continue to be drawn along continental lines, recapitulating previously used racial distinctions: African, European, Native American, and so on.

Although ancestry estimation has the potential to control biases due to genetic confounding, in isolation its use defers, rather than addresses, the important problem of how social and biological risk factors interact in the context of health - including the production of racial health disparities. Research that simultaneously assesses both genetic and environmental contributions to disease risk, drug response and other health-related variation, and that deliberately puts such findings in the context of self-identified race, is urgently needed [13, 41–43]. In the absence of such additional evidence, and despite its amorphous nature, the multi-dimensional and contested concept of race will probably continue to have an important place in biomedical research for many years to come.

The continuing salience of race as a research variable places researchers in the unenviable position of having to negotiate complicated, and often controversial, terrain. Given the potential for misinterpretation and misapplication of research findings, great care must be used in the characterization of study samples and the interpretation of observations (Box 2). Available research tells us that such rigor is often absent in the reporting of race and ethnicity in the biomedical literature [44–50]. In addition, researchers must remain aware of the manner in which their work could be translated, both clinically and in the popular press (Box 2).

How can we move forward? Many journals, research entities and academic commentators have provided relevant recommendations (Box 2). Yet concerns persist, and race and related concepts continue to be used in an inconsistent and potentially misleading manner within biomedical research [44, 48–50].

The concept of race has a long and complex social history [51], and the research community operates within the constraints imposed by this history and its associated social structures. This overriding reality is one of the primary reasons why the use of race remains a controversial and uneasy concept in research. However, there are other challenges that make progress difficult, despite the numerous policy recommendations. Understanding these tendencies, trends and social forces may help us to more effectively use existing recommendations and address social concerns. What follows, although not comprehensive, is a list of some of the most salient challenges that emerged from the workshop.

Race is best understood as the result of a process informed by social values and institutional practices that imbue superficial differences between groups, such as skin color, eye shape or language, with unwarranted significance. Historically, this has been informed by hierarchical thinking, in which group differences and social inequalities are naturalized and rearticulated as biological realities [66]. Genomic research that uses racial categories in the investigation of genetic contributions to disease can also inadvertently support such 'racialization' and influence how findings of group differences are interpreted and, in turn, translated into clinical care and health policy.

Clearly, although the recognition that certain susceptibility variants are more prevalent in certain groups can have health benefits, such observations should not validate the politically and historically charged concept of race or support assumptions that the entire range of attributes ascribed to race have a biological basis. There is a need to develop strategies to mitigate the inappropriate and potentially inaccurate use of categorizing terminology. The available recommendations, outlined in Box 2, have merit. But there are numerous social forces and tendencies, such as those outlined above, that challenge progress towards constructive change.

Future policy and social-science work should focus on exploring the influence of these social forces. For example, although some research in this area has already been done [62, 67], a more nuanced understanding of how data on human genomic variation are interpreted by media, and in turn assimilated by the public, is needed. Recommendations for communication strategy could be used to raise the awareness of researchers as to how their work is apprehended by lay audiences (Box 2), especially journalists. Engagement and education of both scientists and media on their social and ethical responsibilities would be a related actionable strategy (Box 2). In the arena of clinical trials and genetic epidemiological research, the social impact and scientific utility of alternative methods of subject identification and reporting of findings could be explored. Most importantly, consideration should be given not only to ensuring that relevant policy recommendations are effectively implemented, but that they are being followed.

Finally, it must be recognized that the discussion and analysis surrounding the use of race, ethnicity or ancestry in medicine is, for the most part, flowing from scholars in North America and Europe. However, a number of countries, including Mexico, India [68, 69], Thailand and South Africa, are already doing, or planning to undertake, projects studying human genetic diversity within their own populations; and in many others, such as Brazil, extensive admixture has created a continuum of ancestral proportions among individuals that challenge racial classification. It will therefore be important that experts from communities in both the emerging economies and developing countries also contribute to this very important debate.

The following file is available: Additional data file 1 , consisting of an extended version of Box 1 that includes supporting quotations from the cited references for each example concern.