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Comparing Genetic Ancestry and Self-Described Race in African Americans Born in the United States and in Africa

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Comparing Genetic Ancestry and Self-Described Race in African Americans Born in the United States and in Africa 1329 Comparing Genetic Ancestry and Self-Described Race in African Americans Born in the United States and in Africa Rona Yaeger,1 Alexa Avila-Bront,2 Kazeem Abdul,1 Patricia C. Nolan,2 Victor R. Grann,2 Mark G. Birchette,4 Shweta Choudhry,7 Esteban G. Burchard,7 Kenneth B. Beckman,6 Prakash Gorroochurn,3 Elad Ziv,8 Nathan S. Consedine,5 and Andrew K. Joe1,2 1Herbert Irving Comprehensive Cancer Center, 2Department of Medicine, College of Physicians and Surgeons of Columbia University, 3Department of Biostatistics, Columbia University Medical Center, New York, New York; Departments of 4Biology and 5Psychology, Long Island University, Brooklyn, New York; 6Children’s Hospital Oakland Research Institute, Oakland, California; and 7Departments of Biopharmaceutical Sciences and Medicine and 8Division of General Internal Medicine, Department of Medicine, Institute for Human Genetics, Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California Abstract Genetic association studies can be used to identify American in the African American cohort. Therefore, factors that may contribute to disparities in disease self-identification as African American agreed well evident across different racial and ethnic populations. with inferred west African ancestry. However, the However, such studies may not account for potential cohorts differed significantly in mean percentage west confounding if study populations are genetically African and European ancestries (P < 0.0001) and in the heterogeneous. Racial and ethnic classifications have variance for individual ancestry (P V 0.01). Among been used as proxies for genetic relatedness. We African Americans, no set of questionnaire items investigated genetic admixture and developed a ques- effectively estimated degree of west African ancestry, tionnaire to explore variables used in constructing and self-report of a high degree of African ancestry in a racial identity in two cohorts: 50 African Americans three-generation family tree did not accurately predict and 40 Nigerians. Genetic ancestry was determined by degree of African ancestry. Our findings suggest that genotyping 107 ancestry informative markers. Ancestry self-reported race and ancestry can predict ancestral estimates calculated with maximum likelihood estima- clusters but do not reveal the extent of admixture. tion were compared with population stratification Genetic classifications of ancestry may provide a detected with principal components analysis. Ancestry more objective and accurate method of defining homo- was approximately 95% west African, 4% European, genous populations for the investigation of specific and 1% Native American in the Nigerian cohort and population-disease associations. (Cancer Epidemiol 83% west African, 15% European, and 2% Native Biomarkers Prev 2008;17(6):1329–38) Introduction Genome-wide case-control association studies provide a specific racial and ethnic groups (1). Association studies powerful tool for investigating possible genetic factors can most easily identify disease-associated alleles when that may contribute to the health disparities observed study groups are genetically similar, sharing a similar among different racial and ethnic populations. Popula- ancestral background (2). However, individual ancestry tions with different ancestral backgrounds may carry is not an easily assayed, simple category; consequently, different genetic variants, and these may contribute to race continues to be used as a proxy for genetic the variations in disease incidence and outcomes seen in relatedness in clinical and other biological studies (3-6). There is currently no consensus on how best to examine or characterize different racial or ethnic groups Received 8/26/07; revised 4/3/08; accepted 4/9/08. when designing and conducting such studies. Grant support: Long Island University/Herbert Irving Comprehensive Cancer Center Two main approaches have been used to approximate Minority Institution/Cancer Center Partnership grants CA91372, CA101388, and individual ancestry in biological studies: (a) using self- CA101598 (A.K. Joe, N.S. Consedine, and M.G. Birchette); NIH fellowship T32CA09529 (R. Yaeger); National Center for Minority Health Disparities Center of identified race and ethnicity, which may capture com- Excellence in Nutritional Genomics grant 5P60MD00022 (K.B. Beckman); mon environmental influences as well as ancestral Tobacco-Related Disease Research Program New Investigator Award 15KT-0008 b (S. Choudhry); and National Institute of Heart, Lung and Blood grant R01 HL078885, background, and ( ) genotyping a panel of markers that R.W.J. Amos Medical Faculty Development Award, National Center on Minority show large frequency differentials between major Health and Health Disparities Health Disparities Scholar, Extramural Clinical geographic ancestral groupings (7, 8). Both approaches Research Loan Repayment Program for Individuals from Disadvantaged Backgrounds (2001-2003), Sandler Center for Basic Research in Asthma, and Sandler have limitations. Self-identified racial categories may not Family Supporting Foundation (E.G. Burchard). always consistently predict ancestral population clusters, Requests for reprints: Andrew K. Joe, Department of Medicine, College of Physicians and evidence suggests that it may take large sample and Surgeons of Columbia University, 701 West 168th Street, HHSC 1509, New York, NY 10032. Phone: 212-305-6916; Fax: 212-305-6889. E-mail: [email protected] sizes and numerous markers to describe genetic clusters Copyright D 2008 American Association for Cancer Research. that correspond to self-identified race and ethnicity doi:10.1158/1055-9965.EPI-07-2505 groupings (9-11). Racial categories are also imprecise Cancer Epidemiol Biomarkers Prev 2008;17(6). June 2008 Downloaded from cebp.aacrjournals.org on September 25, 2021. © 2008 American Association for Cancer Research. 1330 African American Ancestry Study and inconsistent, because they may potentially vary of Long Island University. Study recruitment was within the same individual over time (12, 13). Further- conducted in collaboration with the Herbert Irving more, their use risks reinforcing racial divisions in Comprehensive Cancer Center Research Recruitment society. On the other hand, more objective analyses that and Minority Outreach Core, a shared facility for genotype markers that are highly informative for recruitment and retention of human subjects in clinical ancestry may not be economically practical and are research, which maintains a strong commitment to limited by the requirement of serum or fresh tissue for recruiting minority subjects to clinical trials. This study DNA extraction. Genetically determined ancestry may was approved by the Columbia University Medical not capture unmeasured social factors that may affect Center Institutional Review Board (Protocol AAAA1500) differences in health outcomes. There are also unique and Long Island University Institutional Review Board. ethical challenges when linking biological phenotypes Subjects were screened for participation using the with genetic markers for specific racial groups, and following criteria: African Americans (subjects identified caution must always be used when attributing biological themselves as African American born in the United differences (e.g., disease risk and treatment response) to States and identified both parents as African Americans different populations. who were born in the United States) and Nigerians Understanding the ancestral background of study (subjects were from the Yoruba or Ibo cultures and were subjects is most important in genetic studies of admixed either born in Nigeria or both parents were born in populations, such as African Americans, who represent Nigeria and immigrated to the United States). These an admixture of Africans, Europeans, and Native were the only entry criteria for study participation, and Americans (14). Genetic studies have shown that African medical history information was not collected during Americans form a diverse group with percent European screening. Subjects consented to participation in the admixture estimated to range between 7% and 23% study, donated blood specimens, and completed ques- (14-16). Genotyping of self-identified African Americans tionnaires at the General Clinical Research Center at participating in the Cardiovascular Health Study the Irving Center for Clinical Research of Columbia revealed that among self-reported Africans there are University, Columbia University Medical Center (Protocol differences in genetic ancestry that are correlated with 3324). Subjects received $40 compensation after complet- some clinically important endpoints (15). ing all aspects of the study. In this study, we compared the degree of genetic Ancestral Populations. Ancestral groups that were admixtureintwocohorts,AfricanAmericansand studied consisted of west African, European, and Native Nigerians, by genotyping a panel of 107 single nucleotide American populations. The west African ancestral polymorphisms (SNP) that are highly informative for population consisted of 37 people from west Africa, ancestry [ancestry informative markers (AIM)]. We and DNA samples were provided by Paul McKeigue. developed a 26-item questionnaire to explore the We specifically chose to focus on west Africa because variables used in constructing racial identity. We the history of African Americans reflects the forced assessed how well self-reported race and ancestry migration of slaves from mainly
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