Race and ancestry in biomedical research: exploring the challenges

Posted in Articles, Health/Medicine/Genetics, Media Archive, Politics/Public Policy on 2013-10-13 18:43Z by Steven

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.

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Categorization of humans in biomedical research: genes, race and disease

Posted in Articles, Health/Medicine/Genetics, Media Archive on 2010-11-12 02:49Z by Steven

Categorization of humans in biomedical research: genes, race and disease

Genome Biology 2002
Volume 3, Number 7
2002-07-01
Print ISSN 1465-6906; Online ISSN 1465-6914
DOI: 10.1186/gb-2002-3-7-comment2007

Neil Risch
Department of Genetics
Stanford University School of Medicine, Stanford, California

Esteban Burchard
Department of Medicine
University of California, San Francisco, California

Elad Ziv
Department of Medicine
University of California, San Francisco, California

Hua Tang
Department of Statistics
Stanford University, Stanford, California

Opinion

A debate has arisen regarding the validity of racial/ethnic categories for biomedical and genetic research. Some claim ‘no biological basis for race’ while others advocate a ‘race-neutral’ approach, using genetic clustering rather than self-identified ethnicity for human genetic categorization. We provide an epidemiologic perspective on the issue of human categorization in biomedical and genetic research that strongly supports the continued use of self-identified race and ethnicity.

A major discussion has arisen recently regarding optimal strategies for categorizing humans, especially in the United States, for the purpose of biomedical research, both etiologic and pharmaceutical. Clearly it is important to know whether particular individuals within the population are more susceptible to particular diseases or most likely to benefit from certain therapeutic interventions. The focus of the dialogue has been the relative merit of the concept of ‘race’ or ‘ethnicity’, especially from the genetic perspective. For example, a recent editorial in the New England Journal of Medicine [1] claimed that “race is biologically meaningless” and warned that “instruction in medical genetics should emphasize the fallacy of race as a scientific concept and the dangers inherent in practicing race-based medicine.” In support of this perspective, a recent article in Nature Genetics [2] purported to find that “commonly used ethnic labels are both insufficient and inaccurate representations of inferred genetic clusters.” Furthermore, a supporting editorial in the same issue [3] concluded that “population clusters identified by genotype analysis seem to be more informative than those identified by skin color or self-declaration of ‘race’.” These conclusions seem consistent with the claim that “there is no biological basis for ‘race’” [3] and that “the myth of major genetic differences across ‘races’ is nonetheless worth dismissing with genetic evidence” [4]. Of course, the use of the term “major” leaves the door open for possible differences but a priori limits any potential significance of such differences.

In our view, much of this discussion does not derive from an objective scientific perspective. This is understandable, given both historic and current inequities based on perceived racial or ethnic identities, both in the US and around the world, and the resulting sensitivities in such debates. Nonetheless, we demonstrate here that from both an objective and scientific (genetic and epidemiologic) perspective there is great validity in racial/ethnic self-categorizations, both from the research and public policy points of view…

…Admixture and genetic categorization in the United States…

What are the implications of these census results and the admixture that has occurred in the US population for genetic categorization in biomedical research studies in the US? Gene flow from non-Caucasians into the US Caucasian population has been modest. On the other hand, gene flow from Caucasians into African Americans has been greater; several studies have estimated the proportion of Caucasian admixture in African Americans to be approximately 17%, ranging regionally from about 12% to 23% [22]. Thus, despite the admixture, African Americans remain a largely African group, reflecting primarily their African origins from a genetic perspective. Asians and Pacific Islanders have been less influenced by admixture and again closely represent their indigenous origins. The same is true for Native Americans, although some degree of Caucasian admixture has occurred in this group as well [23]…

Read the entire opinion here.

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Genetic Ancestry in Lung-Function Predictions

Posted in Articles, Health/Medicine/Genetics, New Media, United States on 2010-07-10 01:51Z by Steven

Genetic Ancestry in Lung-Function Predictions

New England Journal of Medicine
2010-07-07
DOI: 10.1056/NEJMoa0907897

Rajesh Kumar, M.D.
Max A. Seibold, Ph.D.
Melinda C. Aldrich, Ph.D., M.P.H.
L. Keoki Williams, M.D., M.P.H.
Alex P. Reiner, M.D.
Laura Colangelo, M.S.
Joshua Galanter, M.D.
Christopher Gignoux, M.S.
Donglei Hu, Ph.D.
Saunak Sen, Ph.D.
Shweta Choudhry, Ph.D.
Edward L. Peterson, Ph.D.
Jose Rodriguez-Santana, M.D.
William Rodriguez-Cintron, M.D.
Michael A. Nalls, Ph.D.
Tennille S. Leak, Ph.D.
Ellen O’Meara, Ph.D.
Bernd Meibohm, Ph.D.
Stephen B. Kritchevsky, Ph.D.
Rongling Li, M.D., Ph.D., M.P.H.
Tamara B. Harris, M.D.
Deborah A. Nickerson, Ph.D.
Myriam Fornage, Ph.D.
Paul Enright, M.D.
Elad Ziv, M.D.
Lewis J. Smith, M.D.
Kiang Liu, Ph.D.
Esteban González Burchard, M.D., M.P.H.

ABSTRACT

Background Self-identified race or ethnic group is used to determine normal reference standards in the prediction of pulmonary function. We conducted a study to determine whether the genetically determined percentage of African ancestry is associated with lung function and whether its use could improve predictions of lung function among persons who identified themselves as African American.

Methods We assessed the ancestry of 777 participants self-identified as African American in the Coronary Artery Risk Development in Young Adults (CARDIA) study and evaluated the relation between pulmonary function and ancestry by means of linear regression. We performed similar analyses of data for two independent cohorts of subjects identifying themselves as African American: 813 participants in the Health, Aging, and Body Composition (HABC) study and 579 participants in the Cardiovascular Health Study (CHS). We compared the fit of two types of models to lung-function measurements: models based on the covariates used in standard prediction equations and models incorporating ancestry. We also evaluated the effect of the ancestry-based models on the classification of disease severity in two asthma-study populations.

Results African ancestry was inversely related to forced expiratory volume in 1 second (FEV1) and forced vital capacity in the CARDIA cohort. These relations were also seen in the HABC and CHS cohorts. In predicting lung function, the ancestry-based model fit the data better than standard models. Ancestry-based models resulted in the reclassification of asthma severity (based on the percentage of the predicted FEV1) in 4 to 5% of participants.

Conclusions Current predictive equations, which rely on self-identified race alone, may misestimate lung function among subjects who identify themselves as African American. Incorporating ancestry into normative equations may improve lung-function estimates and more accurately categorize disease severity. (Funded by the National Institutes of Health and others.)

…There are some important limitations of our study. First, our analysis does not address population groups other than self-identified African Americans, such as Latinos, who have more complex patterns of ancestral admixture. Second, the association between lung function and ancestry found in our study may be the result of factors other than genetic variation, such as premature birth, prenatal nutrition, socioeconomic status, and other environmental factors. Third, we did not study a replication population with the same age range as that of the CARDIA cohort. Thus, we may have overestimated the association between ancestry and lung function in the CARDIA participants, who were young adults. Finally, some researcher groups used different statistical approaches to estimate ancestry in their respective study populations. We have found previously, however, that different approaches (e.g., Markov models and maximum-likelihood estimation) produce highly correlated results from the same set of markers. The consistency of our findings across three cohorts, despite the different methods for estimating ancestry, underscores the robustness of the association with ancestry…

Read the entire article/report here.

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The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice

Posted in Articles, Health/Medicine/Genetics, Media Archive, United States on 2010-07-10 01:40Z by Steven

The Importance of Race and Ethnic Background in Biomedical Research and Clinical Practice

New England Journal of Medicine
2003-03-20
Volume 348, Number 12
pages 1170-1175

Esteban González Burchard, M.D.
Elad Ziv, M.D.
Natasha Coyle, Ph.D.
Scarlett Lin Gomez, Ph.D.
Hua Tang, Ph.D.
Andrew J. Karter, Ph.D.
Joanna L. Mountain, Ph.D.
Eliseo J. Pérez-Stable, M.D.
Dean Sheppard, M.D.
Neil Risch, Ph.D.

A debate has recently arisen over the use of racial classification in medicine and biomedical research. In particular, with the completion of a rough draft of the human genome, some have suggested that racial classification may not be useful for biomedical studies, since it reflects “a fairly small number of genes that describe appearance” and “there is no basis in the genetic code for race.” In part on the basis of these conclusions, some have argued for the exclusion of racial and ethnic classification from biomedical research. In the United States, race and ethnic background have been used as cause for discrimination, prejudice, marginalization, and even subjugation. Excessive focus on racial or ethnic differences runs the risk of undervaluing the great diversity that exists among persons within groups. However, this risk needs to be weighed against the fact that in epidemiologic and clinical research, racial and ethnic categories are useful for generating and exploring hypotheses about environmental and genetic risk factors, as well as interactions between risk factors, for important medical outcomes. Erecting barriers to the collection of information such as race and ethnic background may provide protection against the aforementioned risks; however, it will simultaneously retard progress in biomedical research and limit the effectiveness of clinical decision making.

Race and Ethnic Background as Geographic and Sociocultural Constructs with Biologic Ramifications

Definitions of race and ethnic background have often been applied inconsistently. The classification scheme used in the 2000 U.S. Census, which is often used in biomedical research, includes five major groups: black or African American, white, Asian, native Hawaiian or other Pacific Islander, and American Indian or Alaska native. In general, this classification scheme emphasizes the geographic region of origin of a person’s ancestry. Ethnic background is a broader construct that takes into consideration cultural tradition, common history, religion, and often a shared genetic heritage…

Sociocultural Correlates of Race and Ethnic Background

The racial or ethnic groups described above do not differ from each other solely in terms of genetic makeup, especially in a multiracial and multicultural society such as the United States. Socioeconomic status is strongly correlated with race and ethnic background and is a robust predictor of access to and quality of health care and education, which, in turn, may be associated with differences in the incidence of diseases and the outcomes of those diseases. For example, black Americans with end-stage renal disease are referred for renal transplantation at lower rates than white Americans. Black Americans are also referred for cardiac catheterization less frequently than white Americans. In some cases, these differences may be due to bias on the part of physicians and discriminatory practices in medicine. Nonetheless, racial or ethnic differences in the outcomes of disease sometimes persist even when discrepancies in the use of interventions known to be beneficial are considered. For example, the rate of complications from type 2 diabetes mellitus varies according to racial or ethnic category among members of the same health maintenance organization, despite uniform utilization of outpatient services and after adjustment for levels of education and income, health behavior, and clinical characteristics. The evaluation of whether genetic (as well as nongenetic) differences underlie racial disparities is appropriate in cases in which important racial and ethnic differences persist after socioeconomic status and access to care are properly taken into account…

…Racially Admixed Populations

Although studies of population genetics have clustered persons into a small number of groups corresponding roughly to five major racial categories, such classification is not completely discontinuous, because there has been intermixing among groups both over the course of history and in recent times. In particular, genetic admixture, or the presence in a population of persons with multiple races or ethnic backgrounds, is well documented in the border regions of continents and may represent genetic gradations (clines) — for example, among East Africans (e.g., Ethiopians) and some central Asian groups. In the United States, mixture among different racial groups has occurred recently, although in the 2000 U.S. Census, the majority of respondents still identified themselves as members of a single racial group. Genetic studies of black Americans have documented a range of 7 to 20 percent white admixture, depending on the geographic location of the population studied. Despite the admixture, black Americans, as a group, are still genetically similar to Africans. Hispanics, the largest and fastest growing minority population in the United States, are an admixed group that includes white and Native American ancestry, as well as African ancestry. The proportions of admixture in this group also vary according to geographic region.

Although the categorization of admixed groups poses special challenges, groups containing persons with varying levels of admixture can also be particularly useful for genetic-epidemiologic studies. For example, Williams et al. studied the association between the degree of white admixture and the incidence of type 2 diabetes mellitus among Pima Indians. They found that the self-reported degree of white admixture (reported as a percentage) was strongly correlated with protection from diabetes in this population. Furthermore, as noted above, information on race or ethnic background can provide important clues to effects of culture, access to care, and bias on the part of caregivers, even in genetically admixed populations. It is also important to recognize that many groups (e.g., most Asian groups) are highly underrepresented both in the population of the United States and in typical surveys of population genetics, relative to their global numbers. Thus, primary categories that are relevant for the current U.S. population might not be optimal for a globally derived sample…

Read the entire article here.

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Genetic screening may redefine medical treatments

Posted in Articles, Health/Medicine/Genetics, New Media, United States, Videos on 2010-07-10 01:21Z by Steven

Genetic screening may redefine medical treatments

KGO-TV San Francisco, California
2010-07-07

Carolyn Johnson, Co-Anchor
KGO-TV

SAN FRANCISCO (KGO) — New research out of UCSF [University of California, San Francisco] shows that tracking a patient’s genetic ancestry can improve the diagnosis of asthma and other lung diseases. The results could have broader implications for other diseases that also rely on standard benchmarks such as race, gender and age.

Doctor’s office visits are the norm for 9-year-old Shamatay Hayes. She was diagnosed with asthma at age 2, something she and her mom have struggled to keep under control.

“It is challenging,” her mother says.

At San Francisco General Hospital and at asthma clinic across the country, Shamatay’s lung function is tracked using standard benchmarks such as age, gender and race. But, researchers say there is now a better way.

“So, what we can now do with modern techniques is estimate what a person’s ancestry is or what their heritage is using a series of genetic markers,” says UCSF researcher Dr. Melinda Aldrich.

The genetic markers more accurately determine lung function rather than a patient’s self-identification as simply white, black or Hispanic.

“With increasing African ancestry, we saw a decrement in lung function,” says UCSF associate professor Dr. Esteban Burchar

…”We’ve had people contact us who were supremacists that said you know what you’re doing is validating what we believe,” he says.

But, the research actually tells a different story.

“Most of us, all of us in fact, are racially mixed,” he says. “We have a very rich heritage and what we’re doing is acknowledging that mixture and incorporating it into our clinical assessments.”…

Read the entire article and view the video clip here.

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Genetic ancestry data improve diagnosis in asthma and lung disease

Posted in Articles, Health/Medicine/Genetics, New Media, United States on 2010-07-09 21:57Z by Steven

Genetic ancestry data improve diagnosis in asthma and lung disease

University of California, San Fransisco
News Release
2010-07-07

Kristen Bole

Released Jointly by UCSF and Northwestern University Feinberg School of Medicine, Henry Ford Hospital, and National Jewish Health

Americans with lung disease may face a far greater level of lung damage than either they or their doctor suspect, depending on their individual genetic heritage, according to a study released July 7. The research implications range from diagnosing the severity of asthma to disability decisions or eligibility for lung transplants, researchers say.

In the largest study of its kind to date, spanning a dozen research centers and pooling data on more than 3,000 patients, a team of researchers led by UCSF and Northwestern University found that patients’ precise genetic background told far more about their potential lung function – and therefore any damage that has occurred – than the self-identified racial profile commonly used in such tests.

The results point to a more precise method of assessing patients’ lung function, as well as the potential impact of using precise genetic benchmarks for assessing health overall, researchers say. Findings will appear in the July 22 print edition of the “New England Journal of Medicine” and online on July 7 at nejm.org.

…Standard race categories, however, don’t capture the extent of our ancestral diversity, according to the paper’s senior author, Esteban G. Burchard, MD, MPH, who is director of the UCSF Center for Genes, Environment and Health, and a member of the Department of Bioengineering and Therapeutic Sciences, a joint department between the UCSF schools of Medicine and Pharmacy.

“People throughout the world have a richer genetic heritage than can be captured by our current definitions of race,” Burchard said, noting that almost every continent has large populations that are known to be genetically mixed. “When we force patients into an individual box, such as ‘African-American’ or ‘Caucasian’, we’re missing a lot of genetic information.”

While this study focused on patients who define themselves as African-Americans, the participants’ actual genetic ancestry ranged broadly and included Caucasian and African heritage

To read the entire article, click here.

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