Mixed Race Studies

Characterizing Race/Ethnicity and Genetic Ancestry for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort

Genetics
August 1, 2015, Volume 200, Number 4
pages 1285-1295
DOI: 10.1534/genetics.115.178616

Yambazi Banda
Mark N. Kvale
Thomas J. Hoffmann
Stephanie E. Hesselson
Dilrini Ranatunga
Hua Tang
Chiara Sabatti
Lisa A. Croen
Brad P. Dispensa
Mary Henderson
Carlos Iribarren
Eric Jorgenson
Lawrence H. Kushi
Dana Ludwig
Diane Olberg
Charles P. Quesenberry Jr.
Sarah Rowell
Marianne Sadler
Lori C. Sakoda
Stanley Sciortino
Ling Shen
David Smethurst
Carol P. Somkin
Stephen K. Van Den Eeden
Lawrence Walter
Rachel A. Whitmer
Pui-Yan Kwok
Catherine Schaefer
Neil Risch

Using genome-wide genotypes, we characterized the genetic structure of 103,006 participants in the Kaiser Permanente Northern California multi-ethnic Genetic Epidemiology Research on Adult Health and Aging Cohort and analyzed the relationship to self-reported race/ethnicity. Participants endorsed any of 23 race/ethnicity/nationality categories, which were collapsed into seven major race/ethnicity groups. By self-report the cohort is 80.8% white and 19.2% minority; 93.8% endorsed a single race/ethnicity group, while 6.2% endorsed two or more. Principal component (PC) and admixture analyses were generally consistent with prior studies. Approximately 17% of subjects had genetic ancestry from more than one continent, and 12% were genetically admixed, considering only nonadjacent geographical origins. Self-reported whites were spread on a continuum along the first two PCs, indicating extensive mixing among European nationalities. Self-identified East Asian nationalities correlated with genetic clustering, consistent with extensive endogamy. Individuals of mixed East Asian–European genetic ancestry were easily identified; we also observed a modest amount of European genetic ancestry in individuals self-identified as Filipinos. Self-reported African Americans and Latinos showed extensive European and African genetic ancestry, and Native American genetic ancestry for the latter. Among 3741 genetically identified parent–child pairs, 93% were concordant for self-reported race/ethnicity; among 2018 genetically identified full-sib pairs, 96% were concordant; the lower rate for parent–child pairs was largely due to intermarriage. The parent–child pairs revealed a trend toward increasing exogamy over time; the presence in the cohort of individuals endorsing multiple race/ethnicity categories creates interesting challenges and future opportunities for genetic epidemiologic studies.

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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…

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