Genome-wide association study identifies common variants associated with breast cancer in South African Black women

Mahtaab Hayat; Wenlong C Chen; Chantal Babb de Villiers; Sang Lee; Charles Curtis; Robert Newton; Tim Waterboer; Freddy Sitas; Debbie Bradshaw; Mazvita Muchengeti; Elvira Singh; Cathryn Lewis; Michele Ramsay; Christopher G Mathew; Jean-Tristan Brandenburg

doi:10.1038/s41467-025-58789-0

Genome-wide association study identifies common variants associated with breast cancer in South African Black women

Mahtaab Hayat, Wenlong C Chen, Chantal Babb de Villiers, Sang Lee, Charles Curtis, Robert Newton, Tim Waterboer, Freddy Sitas, Debbie Bradshaw, Mazvita Muchengeti, Elvira Singh, Cathryn Lewis, Michele Ramsay, Christopher G Mathew, Jean-Tristan Brandenburg

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Abstract

Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10⁻⁰⁸) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10⁻⁰⁸). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The novel loci did not replicate in BC GWAS data from populations of West Africa ancestry suggesting genetic heterogeneity in different African populations, but further validation of these findings is needed. A European ancestry derived polygenic risk model for BC explained only 0.79% of variance in our data. Larger studies in pan-African populations are needed to further define the genetic contribution to BC risk.

Original language	English
Article number	3542
Number of pages	11
Journal	Nature Communications
Volume	16
Issue number	1
Early online date	14 Apr 2025
DOIs	https://doi.org/10.1038/s41467-025-58789-0
Publication status	E-pub ahead of print - 14 Apr 2025

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Hayat, M., Chen, W. C., Babb de Villiers, C., Lee, S., Curtis, C., Newton, R., Waterboer, T., Sitas, F., Bradshaw, D., Muchengeti, M., Singh, E., Lewis, C., Ramsay, M., Mathew, C. G., & Brandenburg, J.-T. (2025). Genome-wide association study identifies common variants associated with breast cancer in South African Black women. Nature Communications, 16(1), Article 3542. Advance online publication. https://doi.org/10.1038/s41467-025-58789-0

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title = "Genome-wide association study identifies common variants associated with breast cancer in South African Black women",

abstract = "Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10−08) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10−08). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The novel loci did not replicate in BC GWAS data from populations of West Africa ancestry suggesting genetic heterogeneity in different African populations, but further validation of these findings is needed. A European ancestry derived polygenic risk model for BC explained only 0.79% of variance in our data. Larger studies in pan-African populations are needed to further define the genetic contribution to BC risk.",

author = "Mahtaab Hayat and Chen, {Wenlong C} and {Babb de Villiers}, Chantal and Sang Lee and Charles Curtis and Robert Newton and Tim Waterboer and Freddy Sitas and Debbie Bradshaw and Mazvita Muchengeti and Elvira Singh and Cathryn Lewis and Michele Ramsay and Mathew, {Christopher G} and Jean-Tristan Brandenburg",

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doi = "10.1038/s41467-025-58789-0",

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Hayat, M, Chen, WC, Babb de Villiers, C, Lee, S , Curtis, C, Newton, R, Waterboer, T, Sitas, F, Bradshaw, D, Muchengeti, M, Singh, E, Lewis, C, Ramsay, M, Mathew, CG & Brandenburg, J-T 2025, 'Genome-wide association study identifies common variants associated with breast cancer in South African Black women', Nature Communications, vol. 16, no. 1, 3542. https://doi.org/10.1038/s41467-025-58789-0

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AU - Hayat, Mahtaab

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AU - Curtis, Charles

AU - Newton, Robert

AU - Waterboer, Tim

AU - Sitas, Freddy

AU - Bradshaw, Debbie

AU - Muchengeti, Mazvita

AU - Singh, Elvira

AU - Lewis, Cathryn

AU - Ramsay, Michele

AU - Mathew, Christopher G

AU - Brandenburg, Jean-Tristan

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AB - Genome-wide association studies (GWAS) have characterized the contribution of common variants to breast cancer (BC) risk in populations of European ancestry, however GWAS have not been reported in resident African populations. This GWAS included 2485 resident African BC cases and 1101 population matched controls. Two risk loci were identified, located between UNC13C and RAB27A on chromosome 15 (rs7181788, p = 1.01 × 10−08) and in USP22 on chromosome 17 (rs899342, p = 4.62 × 10−08). Several genome-wide significant signals were also detected in hormone receptor subtype analysis. The novel loci did not replicate in BC GWAS data from populations of West Africa ancestry suggesting genetic heterogeneity in different African populations, but further validation of these findings is needed. A European ancestry derived polygenic risk model for BC explained only 0.79% of variance in our data. Larger studies in pan-African populations are needed to further define the genetic contribution to BC risk.

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Genome-wide association study identifies common variants associated with breast cancer in South African Black women

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