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
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.


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…

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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
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…

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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

Carolyn Johnson, Co-Anchor

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.”…

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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

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

…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

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