Mixed Race Studies

Characterizing the Admixed African Ancestry of African Americans

Genome Biology
Volume 10, Issue 12 (2009)
R141
DOI: 10.1186/gb-2009-10-12-r141

Fouad Zakharia
Department of Genetics
Stanford University School of Medicine

Analabha Basu
Institute for Human Genetics
University of California, San Francisco

Devin Absher
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama

Themistocles L. Assimes
Division of Cardiovascular Medicine
Stanford University School of Medicine

Alan S. Go
Division of Research
Kaiser Permanente, Oakland, California

Mark A. Hlatky
Department of Health, Research and Policy
Stanford University School of Medicine

Carlos Iribarren
Division of Research
Kaiser Permanente, Oakland, California

Joshua W. Knowles
Division of Cardiovascular Medicine
Stanford University School of Medicine

Jun Li
Department of Human Genetics
University of Michigan

Balasubramanian Narasimhan
Department of Health, Research and Policy
Stanford University School of Medicine

Steven Sidney
Division of Research
Kaiser Permanente, Oakland, California

Audrey Southwick
Department of Infectious Diseases
Stanford University School of Medicine

Richard M. Myers
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama

Thomas Quertermous
Division of Cardiovascular Medicine
Stanford University School of Medicine

Neil Risch
Institute for Human Genetics
University of California, San Francisco

Division of Research
Kaiser Permanente, Oakland, California

Department of Epidemiology and Biostatistics
University of California, San Francisco

Hua Tang
Department of Genetics
Stanford University School of Medicine

Background: Accurate, high-throughput genotyping allows the fine characterization of genetic ancestry. Here we applied recently developed statistical and computational techniques to the question of African ancestry in African Americans by using data on more than 450,000 single-nucleotide polymorphisms (SNPs) genotyped in 94 Africans of diverse geographic origins included in the HGDP, as well as 136 African Americans and 38 European Americans participating in the Atherosclerotic Disease Vascular Function and Genetic Epidemiology (ADVANCE) study. To focus on African ancestry, we reduced the data to include only those genotypes in each African American determined statistically to be African in origin.

Results: From cluster analysis, we found that all the African Americans are admixed in their African components of ancestry, with the majority contributions being from West and West-Central Africa, and only modest variation in these African-ancestry proportions among individuals. Furthermore, by principal components analysis, we found little evidence of genetic structure within the African component of ancestry in African Americans.

Conclusions: These results are consistent with historic mating patterns among African Americans that are largely uncorrelated to African ancestral origins, and they cast doubt on the general utility of mtDNA or Y-chromosome markers alone to delineate the full African ancestry of African Americans. Our results also indicate that the genetic architecture of African Americans is distinct from that of Africans, and that the greatest source of potential genetic stratification bias in case-control studies of African Americans derives from the proportion of European ancestry.

…Although much attention has been paid in the genetics literature to the continental admixture underlying the genetic makeup of African Americans, less attention has been paid to the within-continental contribution to African Americans, in particular from the continent of Africa. Studies have focused primarily on the matrilineally inherited mitochondrial DNA(mtDNA) and patrilineally inherited Y chromosome. These two DNA sources have gained wide prominence owing, in part, to their use by ancestry-testing companies to identify the regional and ethnic origins of their subscribers. Yet these two sources provide a very narrow perspective in delineating only two of possibly thousands of ancestral lineages in an individual.

The majority of African Americans derive their African ancestry from the approximately 500,000 to 650,000 Africans that were forcibly brought to British North America as slaves during the Middle Passage. These individuals were deported primarily from various geographic regions of Western Africa, ranging from Senegal to Nigeria to Angola. Thus, it has been estimated that the majority of African Americans derive ancestry from these geographic regions, although more central and eastern locations also have contributed.  Recent studies of African and African-American mtDNA haplotypes and autosomal microsatellite markers also confirmed a broad range of Western Africa as the likely roots of most African Americans…

Read the entire article here.

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.