Differentiation of African Components of Ancestry to Stratify Groups in a Case–Control Study of a Brazilian Urban Population

Abstract

Background: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. Methods: We explored the applicability of singletube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. Results: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA < 0.25 and > 0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA < 0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. Conclusions: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

PIMA: A population informative multiplex for the Americas

“…These patterns were also previously seen in our studies of Brazilian Kalunga and Sacutiaba [35,36], where no European mtDNA were found (reviewed in [32]). Studies of other groups of the Colombian population of Antioquia [37], found >94% of Y-chromosome lineages were of European origin, while mtDNA was >90% American.…”

“…Highlighted cells indicate three populations with the smallest difference between estimates for the first and second admixture contributor populations (<12%). hypercholesterolemia [35] -underlining the value of simple SNP panels like PIMA to efficiently detect and control ancestry bias in donor samples used in medical genetics. Furthermore, applying the more powerful combination of PIMA+34plex SNPs led to the detection of East Asian co-ancestry in the São Paulo sample, forming a four-way admixture pattern of a predominant European (65%) and African (28%) co-ancestry level overall, but with detectable and consistent East Asian and American admixture components of ∼3.5% each.…”