Self-reported Race Explains One-third of the Variability in African Genetic Ancestry Among Brazilian Patients With Sickle Cell Disease
Year: 2026
Type: article
Abstract: Background Self-reported race is commonly used as a surrogate for genetic ancestry in sickle cell disease (SCD) research, although it represents a social construct rather than a biological measure. The extent to which self-reported race reflects individual African genetic ancestry remains uncertain in highly admixed populations such as Brazilian population. Aims To evaluate the relationship between self-reported race and African genetic ancestry in Brazilian patients with sickle cell disease (HbSS/HbSβ⁰-thalassemia). Methods This real-world multicenter study included patients with HbSS or HbSβ⁰-thalassemia enrolled in the REDS-III Brazil SCD cohort who had available genetic ancestry estimates. Individuals self-identifying as White, Mixed, or Black were compared regarding African (AFR), European (EUR), and Native American (NAM) ancestry proportions. Group differences were assessed using the Kruskal-Wallis test. The association between self-reported race and African genetic ancestry was quantified using linear regression with heteroscedasticity-consistent (HC3) robust standard errors. Adjusted marginal means and pairwise comparisons were estimated using the emmeans package with Holm correction. Results A total of 1,850 SCD patients were included: 190 (10.3%) self-identified as White, 1,112 (60.1%) as Mixed, and 548 (29.6%) as Black individuals. African genetic ancestry increased progressively across self-reported racial groups, whereas European ancestry showed the opposite pattern. NAM ancestry also differed significantly among groups but accounted for only a small proportion of the overall genetic background (all global p<0.001). Adjusted mean African ancestry was 28.9% (95% CI, 27.0–30.8) among White individuals, 42.9% (95% CI, 42.0–43.8) among Mixed individuals, and 64.0% (95% CI, 62.6–65.4) among Black individuals. All pairwise comparisons were statistically significant between all racial groups (Black vs. White: +35.1 percentage points; Black vs. Mixed: +21.1 percentage points; Mixed vs. White: +14.0 percentage points; all Holm-adjusted p<0.001). Despite this clear gradient, self-reported race explained 35.5% of the variability in African genetic ancestry (adjusted R²=0.355), indicating substantial overlap in ancestry distributions among the three racial groups. Discussion and Conclusions Among Brazilian patients with SCD, self-reported race was strongly associated with African genetic ancestry, demonstrating a progressive increase in African ancestry from White to Mixed to Black individuals. However, self-reported race explained only approximately one-third of the variability in African genetic ancestry, highlighting the marked genetic heterogeneity within each racial group. These findings show that self-reported race and genetic ancestry capture are related but distinct dimensions. While self-reported race remains an important demographic and epidemiologic variable it should not be considered an accurate surrogate for individual genetic ancestry in clinical or epidemiological studies.
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223126002