A genome-wide association study identifies an African-specific locus on chromosome 21q22.12 associated with Burkitt lymphoma risk and survival

Dutta, D; Gouveia, MH; Gorman, BR; Adu-Gyamfi, A; Lee, C; Ogwang, MD; Kerchan, P; Reynolds, SJ; Tenge, CN; Were, PA; Wekesa, WN; Tenge, RK; Masalu, N; Kawira, EL; Kinyera, T; Otim, I; Nabalende, H; Dhudha, H; Candia, B; Abaru, J; Yan, W; Florez-Vargas, O; Xie, Y; Ho, M; Mutalima, N

Journal article

A genome-wide association study identifies an African-specific locus on chromosome 21q22.12 associated with Burkitt lymphoma risk and survival

Alternative title:: EPIDEMIOLOGY

Abstract:: Burkitt lymphoma (BL) is a B-cell malignancy that disproportionately affects children in sub-Saharan Africa. We performed a genome-wide association study (GWAS) in a combined set of 800 childhood cases and 3865 controls in East Africa, controlling for age, sex, country, population-specific principal components, and a genetic relationship matrix. This analysis identified a BL-protective region within chromosome 21q22.12 tagged by the rs111457485-T allele (odds ratio [OR] = 0.57; p = 5.7 × 10−9). The results were robust in standard meta-analysis (OR = 0.57, p < 1.6 × 10−8), sensitivity analyses (removing genomic outliers and related individuals), and after adjustment for Epstein-Barr virus (EBV) status. Genomic analyses revealed long-range (over ~700 kb) chromatin interactions between the chr21q22.12 locus and the RUNX1-P1 promoter region. The African-specific rs2242780-C allele (r2 = 0.69 with the rs111457485-T allele in the study controls) showed increased enhancer activity in in-vitro Luciferase reporter assays (p = 4.5 × 10−10), nominating it as the likely functional variant for the BL-associated loci. In addition to the association with reduced BL risk in GWAS (OR = 0.62, p = 2.24 × 10−8), the rs2242780-C allele was also associated with better survival in patients with abdominal-only BL in exploratory analyses (hazard ratio = 0.39, p = 0.038, 106 patients, 59 deaths). Our GWAS uncovered novel BL-protective loci near RUNX1, offering insights into the genetic etiology of BL in African children.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Dutta, D., Gouveia, M. H., Gorman, B. R., Adu-Gyamfi, A., Lee, C., Ogwang, M. D., Kerchan, P., Reynolds, S. J., Tenge, C. N., Were, P. A., Wekesa, W. N., Tenge, R. K., Masalu, N., Kawira, E. L., Kinyera, T., Otim, I., Nabalende, H., Dhudha, H., Candia, B., … Mutalima, N. (2025). A genome-wide association study identifies an African-specific locus on chromosome 21q22.12 associated with Burkitt lymphoma risk and survival. Leukemia, 39(9), 2196–2206.

MLA Style

Dutta, D., et al. “A Genome-Wide Association Study Identifies an African-Specific Locus on Chromosome 21q22.12 Associated with Burkitt Lymphoma Risk and Survival.” Leukemia, vol. 39, no. 9, Springer Nature [academic journals on nature.com], 2025, pp. 2196–206.

Chicago Style

Dutta, D, MH Gouveia, BR Gorman, A Adu-Gyamfi, C Lee, MD Ogwang, P Kerchan, et al. 2025. “A Genome-Wide Association Study Identifies an African-Specific Locus on Chromosome 21q22.12 Associated with Burkitt Lymphoma Risk and Survival.” Leukemia 39 (9): 2196–2206.
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