The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants.
In this study, we compared genetically determined ancestry (GDA) and self-reported race/ethnicity (SRR) in the PHACS cohort. GDA was estimated using a highly discriminative panel of 41 single nucleotide polymorphisms and compared to SRR. Because SRR was similar between the PHIV and PHEU, and between the AMP and SMARTT cohorts, data for all unique 1958 participants were combined.
According to SRR, 63% of study participants identified as Black/African-American, 27% White, and 34% Hispanic. Using the highest percentage of ancestry/ethnicity to identify GDA, 9.5% of subjects were placed in the incorrect superpopulation based on SRR. When ≥50% or ≥75% GDA of a given superpopulation was required, 12% and 25%, respectively, of subjects were placed in the incorrect superpopulation based on SRR, and the percent of subjects classified as multiracial increased. Of 126 participants with unidentified SRR, 71% were genetically identified as Eurasian.
GDA provides a more robust assessment of race/ethnicity when compared to self-report, and study participants with unidentified SRR could be assigned GDA using genetic markers. In addition, identification of continental ancestry removes the taxonomic identification of race as a variable when identifying risk for clinical outcomes.
aUniversity of California, San Diego, La Jolla
bRady Children's Hospital-San Diego, San Diego, CA
cCenter for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA
dAlbert Einstein College of Medicine, Bronx Lebanon Hospital, Bronx, New York, NY
eDepartments of Biostatistics
fEpidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
gEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD
hTulane University School of Medicine, New Orleans, LA.
Correspondence: Stephen A. Spector, University of California, San Diego, 9500 Gilman Drive, Stein Clinical Research Building, MC 0672, La Jolla, CA 92093-0672 (e-mail: email@example.com).
Abbreviations: AIDS = Acquired Immunodeficiency Syndrome, AIMs = ancestry informative markers, AMP Study = Adolescent Master Protocol Study, ART = antiretroviral therapy, ARVs = antiretrovirals, DNA = deoxyribonucleic acid, GDA = genetically determined ancestry, HIV = human immunodeficiency virus, NCS = National Children's Study, PCA = principal component analysis, PCR = polymerase chain reaction, PHACS = Pediatric HIV/AIDS Cohort Study, PHEU = perinatal HIV-exposed, uninfected, PHIV = perinatal HIV-infected, SMARTT Study = Surveillance Monitoring of ART Toxicities Study, SNPs = single nucleotide polymorphisms, SRR = self-reported race/ethnicity.
This research was supported in part by 1R01NS077874 (SAS). The Pediatric HIV/AIDS Cohort Study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with cofunding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the Office of AIDS Research, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Heart Lung and Blood Institute, the National Institute of Dental and Craniofacial Research, and the National Institute on Alcohol Abuse and Alcoholism, through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102; Principal Investigator: George Seage; Project Director: Julie Alperen) and the Tulane University School of Medicine (HD052104; Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Kenneth Rich); Data management services were provided by Frontier Science and Technology Research Foundation (Principal Investigator: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (Principal Investigator: Julie Davidson).
Authors’ contributions: SAS contributed to the conception and design, acquisition of data, analysis and interpretation of data, and wrote the manuscript.
SSB contributed to the conception and design, acquisition of data, analysis and interpretation of data, and critically edited the manuscript.
CMN, AXM, MUP, PLW, RH, RVD, and GRS contributed to the analysis and interpretation of data, and critically edited the manuscript. KKS contributed to the acquisition of data, analysis and interpretation of data, and critically edited the manuscript.
Data presented in this manuscript are available upon request at: https://phacsstudy.org/Our-Research/Data-Request-Form.
The authors have no conflicts of interest to disclose.
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Received April 11, 2016
Received in revised form June 29, 2016
Accepted August 7, 2016