Mixed Race Studies

Human Variation: A Genetic Perspective on Diversity, Race, and Medicine

Cold Spring Harbor Laboratory Press
2014
131 pages
(21 4C, 5B&W), index
Hardcover ISBN: 978-1-621820-90-1
Paperback ISBN: 978-1-936113-25-5

Edited by:

Aravinda Chakravarti, Professor of Medicine, Pediatrics, Molecular Biology & Genetics, and, Biostatistics
Johns Hopkins University School of Medicine, Institute of Genetic Medicine

Since the appearance of modern humans in Africa around 200,000 years ago, we have migrated around the globe and accumulated genetic variations that affect various traits, including our appearance, skin color, food tolerance, and susceptibility to different diseases. Large-scale DNA sequencing is now allowing us to map the patterns of human genetic variation more accurately than ever before, trace our ancestries, and develop personalized therapies for particular diseases. It is also reinforcing the idea that human populations are far from homogeneous, are highly intermixed, and do not fall into distinct races or castes that can be defined genetically.

This book provides a state-of-the-art view of human genetic variation and what we can infer from it, surveying the genetic diversity seen in Africa, Europe, the Americas, and India. The contributors discuss what this can tell us about human history and how it can be used to improve human health. They also caution against assumptions that differences between individuals always stem from our DNA, stressing the importance of nongenetic forces and pointing out the limits of our knowledge. The book is thus essential reading for all human geneticists and anyone interested in how we differ and what this means.

Contents

• Preface
• Perspectives on Human Variation through the Lens of Diversity and Race / Aravinda Chakravarti
• What Type of Person Are You? Old-Fashioned Thinking Even in Modern Science / Kenneth M. Weiss and Brian W. Lambert
• Social Diversity in Humans: Implications and Hidden Consequences for Biological Research / Troy Duster
• Demographic Events and Evolutionary Forces Shaping European Genetic Diversity / Krishna R. Veeramah and John Novembre
• Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease / Felicia Gomez, Jibril Hirbo and Sarah A. Tishkoff
• A Genomic View of Peopling and Population Structure of India / Partha P. Majumder and Analahba Basu
• How Genes Have Illuminated the History of Early Americans and Latino Americans / Andres Ruiz-Linares
• Can Genetics Help Us Understand Indian Social History? / Romila Thapar
• Race in Biological and Biomedical Research / Richard S. Cooper
• Personalized Medicine and Human Genetic Diversity / Yi-Fan Lu, David B. Goldstein, Misha Angrist, and Gianpiero Cavalleri
• Index

The Contribution of Genomic Research to Explaining Racial Disparities in Cardiovascular Disease: A Systematic Review

American Journal of Epidemiology
First Published online: 2015-03-01
DOI: 10.1093/aje/kwu319

Jay S. Kaufman, Professor
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, Quebec, Canada

Lena Dolman
McGill University, Montreal, Quebec, Canada

Dinela Rushani
McGill University, Montreal, Quebec, Canada

Richard S. Cooper, Anthony B. Traub Professor of Community and Family Medicine
Stritch School of Medicine
Loyola University, Chicago, Illinois

After nearly a decade of genome-wide association studies, no assessment has yet been made of their contribution toward an explanation of the most prominent racial health disparities observed at the population level. We examined populations of African and European ancestry and focused on cardiovascular diseases, which are collectively the largest contributor to the racial mortality gap. We conducted a systematic search for review articles and meta-analyses published in 2007–2013 in which genetic data from both populations were available. We identified 68 articles relevant to this question; however, few reported significant associations in both racial groups, with just 3 variants meeting study-specific significance criteria. For most outcomes, there were too few estimates for quantitative summarization, but when summarization was possible, racial group did not contribute to heterogeneity. Most associations reported from genome-wide searches were small, difficult to replicate, and in no consistent direction that favored one racial group or another. Although the substantial investment in this technology might have produced clinical advances, it has thus far made little or no contribution to our understanding of population-level racial health disparities in cardiovascular disease.

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Race in Biological and Biomedical Research

Cold Spring Harbor Perspectives in Medicine
Volume 3, Issue 11 (November 2013)
10 pages
DOI: 10.1101/cshperspect.a008573

Richard S. Cooper, Anthony B. Traub Professor of Community and Family Medicine
Loyola University Medical School

The concept of race has had a significant influence on research in human biology since the early 19th century. But race was given its meaning and social impact in the political sphere and subsequently intervened in science as a foreign concept, not grounded in the dominant empiricism of modern biology. The uses of race in science were therefore often disruptive and controversial; at times, science had to be retrofitted to accommodate race, and science in turn was often used to explain and justify race. This relationship was unstable in large part because race was about a phenomenon that could not be observed directly, being based on claims about the structure and function of genomic DNA. Over time, this relationship has been characterized by distinct phases, evolving from the inference of genetic effects based on the observed phenotype to the measurement of base-pair variation in DNA. Despite this fundamental advance in methodology, liabilities imposed by the dual political-empirical origins of race persist. On the one hand, an optimistic prediction can be made that just as geology made it possible to overturn the myth of the recent creation of the earth and evolution told us where the living world came from, molecular genetics will end the use of race in biology. At the same time, because race is fundamentally a political and not a scientific idea, it is possible that only a political intervention will relieve us of the burden of race.

A Klee painting named Angelus Novus shows an angel looking as though he is about to move away from something he is fixedly contemplating. His eyes are staring, his mouth is open, his wings are spread. His face is turned toward the past. Where we perceive a chain of events, he sees one single catastrophe, which keeps piling wreckage upon wreckage and hurls it in front of his feet. The angel would like to stay, awaken the dead, and make whole what has been smashed. But a storm is blowing from Paradise; it has got caught in his wings with such violence that he cannot close them. The storm irresistibly propels him into the future to which his back is turned, while the pile of debris in front of him grows skyward. This storm is what we call progress.

—Walter Benjamin
Theses on the Philosophy of History

RACE AS THE UNWELCOME GUEST IN THE DISCIPLINES OF SCIENCE

We rarely appreciate the presence of history in our day-to-day experience. The quotidian is a mixture of the repetitive and the predictable, carried forward by habit and punctuated by random events that we regard as either good or bad fortune. But in a more reflective mood, we have to acknowledge the relentless force of history that holds us in its grasp and accept that it creates the possibilities we use to negotiate with the future. The imposition of racial categories on human populations has been one of the most enduring historical forces that sets limits on opportunity and thereby shapes our life trajectory. As a projection of the underlying power relationships onto individuals, racial categories are used to structure social inequality. These power relationships are manifested both in the belief system that rank orders intrinsic human qualities according to group membership and the social institutions that enforce this hierarchy by restricting access to wealth, education, and other social goods. This daily reality is central to the history of all modern societies.

The racial structuring of society also has pervasive influence on biological research and the patterns of health and disease. Enormous effort has been expended to describe human demographic history through reference to an ever-changing array of constructs and categories, all of which include a hierarchical arrangement—either explicit or implicit. In the United States, most prominently, public health has embraced racial/ethnic categories as fundamental structural elements. Clinical medicine has similarly evoked racial categories to explain causation and outcomes across the entire spectrum of diseases. At the same time, race has met some of the strongest challenges to its legitimacy in biology and biomedicine. All of biology is grounded in the theory of descent from a common ancestor. The belief in racial categories was one of the most powerful liabilities of pre-modern biology and lent credence to the established view of divine creation. Indeed, it has recently been argued that the challenge to race brought by the abolitionist movement was a key factor behind Darwin’s transformative insight that the biological world—on the evolutionary time scale—is a single indivisible whole (Desmond and Moore 2009). Biomedicine still grapples with the implications of that insight for our species, yet substantial progress—uneven, tentative, and ultimately disappointing—has been made. In the current era, genomic science has opened new vistas onto previously unobserved dimensions of biology, and that proportion of the concept of race that has been attributed to genetics can finally be subjected to empirical scrutiny. Integrating this new knowledge into practice and focusing the technology on socially productive work, as always, remains our most difficult challenge.

The narrative of race therefore wanders the border territory between what we call science and what we recognize as history and politics. In the pre-genomic era, there was no requirement—indeed, no opportunity—to validate the authority of race with molecular evidence; causal inferences were made on the basis of phenotype, in its broadest possible sense, from disease to accumulated material wealth to social graces. The primary purpose of the race concept was to serve as a shortcut, an organizing tool that allowed post-enlightenment Europe to explain—and thereby justify—how imperialism had reshaped the world. Consequently, for both the social and biological sciences, race felt like the rude cousin whose claim on our affection was based on obligation, not choice. In every historical period, an incremental struggle has been waged to overcome the disruption that this unwelcome intruder has caused within empirical scientific disciplines.

In its origins, race was a “label of convenience” that biologists used interchangeably with the construct of “varieties” as they tried to create taxonomic categories below the level of the species (Cooper 1984). Writers from across the intellectual spectrum of literature and politics also felt free to make use of the idea. Thus, Baudelaire spoke of the “race of Abel” and the “race of Cain” when describing the polarization of 19th-century French society, and Marx characterized the English working class as a “race of peculiar commodity owners” (Baudelaire 1857; Marx 1957) (“Hence the sum of the means of subsistence necessary for the production of labour-power must include the means necessary for the labourer’s substitutes, i.e., his children, in order that this race of peculiar commodity-owners may perpetuate its appearance in the market.” [p. 172]). Malleability continues to be an essential quality of race, although it is now primarily used as a label for the temporary and often random aggregation of population subgroups, usually tied in some rough way to the perceived continent of origin (Kaufman and Cooper 1996). In its contemporary sense, biological race has now come to signify the inherited qualities of a population group hidden inside the DNA molecule…

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Race and ancestry in biomedical research: exploring the challenges

Genome Medicine 2009
Volume 1, Number 8 (2009-01-21)
DOI: 10.1186/gm8

Timothy Caulfield
Faculty of Law and School of Public Health Research, Health Law Institute
University of Alberta

Stephanie M Fullerton
Department of Medical History and Ethics and Department of Genome Sciences
University of Washington School of Medicine

Sarah E Ali-Khan
Program on Life Sciences Ethics and Policy, McLaughlin-Rotman Centre for Global Health, University Health Network
University of Toronto

Laura Arbour
Faculty of Medicine, Island Medical Program
University of British Columbia

Esteban G. Burchard
Department of Biopharmaceutical Sciences and Department of Medicine, Divisions of Pharmaceutical Sciences and Pharmacogenetics, Pulmonary & Critical Care Medicine, and Clinical Pharmacology
University of California, San Francisco

Richard S. Cooper
Department of Epidemiology & Preventive Medicine, Stritch School of Medicine
Loyola University

Billie-Jo Hardy
Program on Life Sciences Ethics and Policy, McLaughlin-Rotman Centre for Global Health, University Health Network
University of Toronto

Simrat Harry
Faculty of Law and School of Public Health Research, Health Law Institute
University of Alberta

Robyn Hyde-Lay
Genome Alberta, Calgary, Alberta, Canada

Jonathan Kahn
Hamline University School of Law

Rick Kittles
Department of Medicine, Section of Genetic Medicine, Department of Human Genetics
University of Chicago

Barbara A. Koenig
Program in Professionalism & Bioethics
Mayo College of Medicine

Sandra S. J. Lee
Stanford Center for Biomedical Ethics
Stanford University Medical School

Michael Malinowski
Paul M Hebert Law Center
Louisiana State University, Baton Rouge

Vardit Ravitsky
Department of Medical Ethics and Center for Bioethics
University of Pennsylvania, Philadelphia

Pamela Sankar
Department of Medical Ethics and Center for Bioethics
University of Pennsylvania, Philadelphia

Stephen W. Scherer
for Applied Genomics, The Hospital for Sick Children, and Department of Molecular Genetics
University of Toronto

Béatrice Séguin
Leslie Dan School of Pharmacy; Program on Life Sciences Ethics and Policy, McLaughlin-Rotman Centre for Global Health, University Health Network
University of Toronto

Darren Shickle
Leeds Institute of Health Sciences,
University of Leeds, United Kingdom

Guilherme Suarez-Kurtz
Pharmacology Division
Instituto Nacional de Câncer, Rio de Janeiro, Brazil

Abdallah S. Daar
Program on Life Sciences Ethics and Policy, McLaughlin-Rotman Centre for Global Health, University Health Network; Department of Public Health Sciences and of Surgery; McLaughlin Centre for Molecular Medicine; Department of Medicine
University of Toronto

The use of race in biomedical research has, for decades, been a source of social controversy. However, recent events, such as the adoption of racially targeted pharmaceuticals, have raised the profile of the race issue. In addition, we are entering an era in which genomic research is increasingly focused on the nature and extent of human genetic variation, often examined by population, which leads to heightened potential for misunderstandings or misuse of terms concerning genetic variation and race. Here, we draw together the perspectives of participants in a recent interdisciplinary workshop on ancestry and health in medicine in order to explore the use of race in research issue from the vantage point of a variety of disciplines. We review the nature of the race controversy in the context of biomedical research and highlight several challenges to policy action, including restrictions resulting from commercial or regulatory considerations, the difficulty in presenting precise terminology in the media, and drifting or ambiguous definitions of key terms.

Correspondence

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…

Read the entire correspondence here.

In conclusion, based on a consecutive series of patients from an urban medical center in New York City we demonstrate that a spectrum of mixed ancestry is emerging in the largest US minority groups. While consistent with previous descriptive studies, when viewed from the clinical perspective this evidence invites a re-evaluation of the relevance of racial/ethnic labels. In combination with evidence of locus heterogeneity within and between populations, this picture of extensive gene flow lends credence to the argument that the transfer of historical population labels which reflect language and other social categories onto patient samples will in many cases be unwarranted.

Tayo BO, Teil M, Tong L, Qin H, Khitrov G, et al., “Genetic Background of Patients from a University Medical Center in Manhattan: Implications for Personalized Medicine,” PLoS ONE, Volume 6, Number 5 (2011-05-04): 8-10. http://dx.doi.org/10.1371/journal.pone.0019166.

Genetic Background of Patients from a University Medical Center in Manhattan: Implications for Personalized Medicine

PLoS ONE: A peer-reviewed, open access journal
Volume 6, Number 5 (2011-05-04)
11 pages
DOI: 10.1371/journal.pone.0019166

Bamidele O. Tayo
Department of Preventive Medicine and Epidemiology
Loyola University Chicago
Stritch School of Medicine, Maywood, Illinois

Marie Teil
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Liping Tong
Department of Preventive Medicine and Epidemiology
Loyola University Chicago
Stritch School of Medicine, Maywood, Illinois

Huaizhen Qin
Department of Biostatistics and Epidemiology
Case Western University, Cleveland, Ohio

Gregory Khitrov
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Weijia Zhang
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Quinbin Song
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Omri Gottesman
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Xiaofeng Zhu
Department of Biostatistics and Epidemiology
Case Western University, Cleveland, Ohio

Alexandre C. Pereira
University of Sao Paulo Medical School, Sao Paulo, Brazil

Richard S. Cooper
Department of Preventive Medicine and Epidemiology
Loyola University Chicago
Stritch School of Medicine, Maywood, Illinois

Erwin P. Bottinger
Charles R. Bronfman Institute for Personalized Medicine
Mount Sinai School of Medicine, New York, New York

Background

The rapid progress currently being made in genomic science has created interest in potential clinical applications; however, formal translational research has been limited thus far. Studies of population genetics have demonstrated substantial variation in allele frequencies and haplotype structure at loci of medical relevance and the genetic background of patient cohorts may often be complex.

Methods and Findings

To describe the heterogeneity in an unselected clinical sample we used the Affymetrix 6.0 gene array chip to genotype self-identified European Americans (N = 326), African Americans (N = 324) and Hispanics (N = 327) from the medical practice of Mount Sinai Medical Center in Manhattan, NY. Additional data from US minority groups and Brazil were used for external comparison. Substantial variation in ancestral origin was observed for both African Americans and Hispanics; data from the latter group overlapped with both Mexican Americans and Brazilians in the external data sets. A pooled analysis of the African Americans and Hispanics from NY demonstrated a broad continuum of ancestral origin making classification by race/ethnicity uninformative. Selected loci harboring variants associated with medical traits and drug response confirmed substantial within- and between-group heterogeneity.

Conclusion

As a consequence of these complementary levels of heterogeneity group labels offered no guidance at the individual level. These findings demonstrate the complexity involved in clinical translation of the results from genome-wide association studies and suggest that in the genomic era conventional racial/ethnic labels are of little value.

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What’s the Use of Race? Modern Governance and the Biology of Difference

The MIT Press
May 2010
7 x 9, 296 pp., 7 illus.
ISBN-10: 0-262-51424-9
ISBN-13: 978-0-262-51424-8

Edited by

Ian Whitmarsh, Assistant Professor
Department of Anthropology, History, and Social Medicine
University of California, San Francisco

David S. Jones, Associate Professor of History and Culture of Science and Technology
Massachusetts Institute of Technology

The post–civil rights era perspective of many scientists and scholars was that race was nothing more than a social construction. Recently, however, the relevance of race as a social, legal, and medical category has been reinvigorated by science, especially by discoveries in genetics. Although in 2000 the Human Genome Project reported that humans shared 99.9 percent of their genetic code, scientists soon began to argue that the degree of variation was actually greater than this, and that this variation maps naturally onto conventional categories of race. In the context of this rejuvenated biology of race, the contributors to What’s the Use of Race? investigate whether race can be a category of analysis without reinforcing it as a basis for discrimination. Can policies that aim to alleviate inequality inadvertently increase it by reifying race differences?

The essays focus on contemporary questions at the cutting edge of genetics and governance, examining them from the perspectives of law, science, and medicine. The book follows the use of race in three domains of governance: ruling, knowing, and caring. Contributors first examine the use of race and genetics in the courtroom, law enforcement, and scientific oversight; then explore the ways that race becomes, implicitly or explicitly, part of the genomic science that attempts to address human diversity; and finally investigate how race is used to understand and act on inequities in health and disease. Answering these questions is essential for setting policies for biology and citizenship in the twenty-first century.

Contributors: Richard Ashcroft, Richard S. Cooper, Kjell A. Doksum, George T. H. Ellison, Steven Epstein, Joan H. Fujimura, Amy Hinterberger, Angela C. Jenks, David S. Jones, Jonathan Kahn, Jay S. Kaufman, Nancy Krieger, Paul Martin, Pilar N. Ossorio, Simon Outram, Ramya Rajagopalan, Dorothy Roberts, Pamela Sankar, Andrew Smart, Richard Tutton, Ian Whitmarsh