Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction

Guochong Jia; Jie Ping; Xingyi Guo; Yaohua Yang; Ran Tao; Bingshan Li; Stefan Ambs; Mollie E. Barnard; Yu Chen; Montserrat Garcia-Closas; Jian Gu; Jennifer J. Hu; Dezheng Huo; Esther M. John; Christopher I. Li; James L. Li; Katherine L. Nathanson; Barbara Nemesure; Olufunmilayo I. Olopade; Tuya Pal; Michael F. Press; Maureen Sanderson; Dale P. Sandler; Xiao Ou Shu; Melissa A. Troester; Song Yao; Prisca O. Adejumo; Thomas Ahearn; Abenaa M. Brewster; Anselm J.M. Hennis; Timothy Makumbi; Paul Ndom; Katie M. O’Brien; Andrew F. Olshan; Mojisola M. Oluwasanu; Sonya Reid; Ebonee N. Butler; Maosheng Huang; Atara Ntekim; Huijun Qian; Haoyu Zhang; Christine B. Ambrosone; Qiuyin Cai; Jirong Long; Julie R. Palmer; Christopher A. Haiman; Wei Zheng

doi:10.1038/s41588-024-01736-4

Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction

Guochong Jia, Jie Ping, Xingyi Guo, Yaohua Yang, Ran Tao, Bingshan Li, Stefan Ambs, Mollie E. Barnard, Yu Chen, Montserrat Garcia-Closas, Jian Gu, Jennifer J. Hu, Dezheng Huo, Esther M. John, Christopher I. Li, James L. Li, Katherine L. Nathanson, Barbara Nemesure, Olufunmilayo I. Olopade, Tuya PalMichael F. Press, Maureen Sanderson, Dale P. Sandler, Xiao Ou Shu, Melissa A. Troester, Song Yao, Prisca O. Adejumo, Thomas Ahearn, Abenaa M. Brewster, Anselm J.M. Hennis, Timothy Makumbi, Paul Ndom, Katie M. O’Brien, Andrew F. Olshan, Mojisola M. Oluwasanu, Sonya Reid, Ebonee N. Butler, Maosheng Huang, Atara Ntekim, Huijun Qian, Haoyu Zhang, Christine B. Ambrosone, Qiuyin Cai, Jirong Long, Julie R. Palmer, Christopher A. Haiman, Wei Zheng

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Abstract

We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10⁻⁸), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

Original language	English (US)
Pages (from-to)	819-826
Number of pages	8
Journal	Nature Genetics
Volume	56
Issue number	5
DOIs	https://doi.org/10.1038/s41588-024-01736-4
State	Published - May 2024

ASJC Scopus subject areas

Genetics

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Jia, G., Ping, J., Guo, X., Yang, Y., Tao, R., Li, B., Ambs, S., Barnard, M. E., Chen, Y., Garcia-Closas, M., Gu, J., Hu, J. J., Huo, D., John, E. M., Li, C. I., Li, J. L., Nathanson, K. L., Nemesure, B., Olopade, O. I., ... Zheng, W. (2024). Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction. Nature Genetics, 56(5), 819-826. https://doi.org/10.1038/s41588-024-01736-4

Jia, G, Ping, J, Guo, X, Yang, Y, Tao, R, Li, B, Ambs, S, Barnard, ME, Chen, Y, Garcia-Closas, M, Gu, J, Hu, JJ, Huo, D, John, EM, Li, CI, Li, JL, Nathanson, KL, Nemesure, B, Olopade, OI, Pal, T, Press, MF, Sanderson, M, Sandler, DP, Shu, XO, Troester, MA, Yao, S, Adejumo, PO, Ahearn, T, Brewster, AM, Hennis, AJM, Makumbi, T, Ndom, P, O’Brien, KM, Olshan, AF, Oluwasanu, MM, Reid, S, Butler, EN, Huang, M, Ntekim, A, Qian, H, Zhang, H, Ambrosone, CB, Cai, Q, Long, J, Palmer, JR, Haiman, CA & Zheng, W 2024, 'Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction', Nature Genetics, vol. 56, no. 5, pp. 819-826. https://doi.org/10.1038/s41588-024-01736-4

@article{e21d049cc6a144ffb53104f0bb17bad9,

title = "Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction",

abstract = "We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10−8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.",

author = "Guochong Jia and Jie Ping and Xingyi Guo and Yaohua Yang and Ran Tao and Bingshan Li and Stefan Ambs and Barnard, {Mollie E.} and Yu Chen and Montserrat Garcia-Closas and Jian Gu and Hu, {Jennifer J.} and Dezheng Huo and John, {Esther M.} and Li, {Christopher I.} and Li, {James L.} and Nathanson, {Katherine L.} and Barbara Nemesure and Olopade, {Olufunmilayo I.} and Tuya Pal and Press, {Michael F.} and Maureen Sanderson and Sandler, {Dale P.} and Shu, {Xiao Ou} and Troester, {Melissa A.} and Song Yao and Adejumo, {Prisca O.} and Thomas Ahearn and Brewster, {Abenaa M.} and Hennis, {Anselm J.M.} and Timothy Makumbi and Paul Ndom and O{\textquoteright}Brien, {Katie M.} and Olshan, {Andrew F.} and Oluwasanu, {Mojisola M.} and Sonya Reid and Butler, {Ebonee N.} and Maosheng Huang and Atara Ntekim and Huijun Qian and Haoyu Zhang and Ambrosone, {Christine B.} and Qiuyin Cai and Jirong Long and Palmer, {Julie R.} and Haiman, {Christopher A.} and Wei Zheng",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

year = "2024",

month = may,

doi = "10.1038/s41588-024-01736-4",

language = "English (US)",

volume = "56",

pages = "819--826",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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TY - JOUR

T1 - Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction

AU - Jia, Guochong

AU - Ping, Jie

AU - Guo, Xingyi

AU - Yang, Yaohua

AU - Tao, Ran

AU - Li, Bingshan

AU - Ambs, Stefan

AU - Barnard, Mollie E.

AU - Chen, Yu

AU - Garcia-Closas, Montserrat

AU - Gu, Jian

AU - Hu, Jennifer J.

AU - Huo, Dezheng

AU - John, Esther M.

AU - Li, Christopher I.

AU - Li, James L.

AU - Nathanson, Katherine L.

AU - Nemesure, Barbara

AU - Olopade, Olufunmilayo I.

AU - Pal, Tuya

AU - Press, Michael F.

AU - Sanderson, Maureen

AU - Sandler, Dale P.

AU - Shu, Xiao Ou

AU - Troester, Melissa A.

AU - Yao, Song

AU - Adejumo, Prisca O.

AU - Ahearn, Thomas

AU - Brewster, Abenaa M.

AU - Hennis, Anselm J.M.

AU - Makumbi, Timothy

AU - Ndom, Paul

AU - O’Brien, Katie M.

AU - Olshan, Andrew F.

AU - Oluwasanu, Mojisola M.

AU - Reid, Sonya

AU - Butler, Ebonee N.

AU - Huang, Maosheng

AU - Ntekim, Atara

AU - Qian, Huijun

AU - Zhang, Haoyu

AU - Ambrosone, Christine B.

AU - Cai, Qiuyin

AU - Long, Jirong

AU - Palmer, Julie R.

AU - Haiman, Christopher A.

AU - Zheng, Wei

PY - 2024/5

Y1 - 2024/5

N2 - We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10−8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

AB - We performed genome-wide association studies of breast cancer including 18,034 cases and 22,104 controls of African ancestry. Genetic variants at 12 loci were associated with breast cancer risk (P < 5 × 10−8), including associations of a low-frequency missense variant rs61751053 in ARHGEF38 with overall breast cancer (odds ratio (OR) = 1.48) and a common variant rs76664032 at chromosome 2q14.2 with triple-negative breast cancer (TNBC) (OR = 1.30). Approximately 15.4% of cases with TNBC carried six risk alleles in three genome-wide association study-identified TNBC risk variants, with an OR of 4.21 (95% confidence interval = 2.66–7.03) compared with those carrying fewer than two risk alleles. A polygenic risk score (PRS) showed an area under the receiver operating characteristic curve of 0.60 for the prediction of breast cancer risk, which outperformed PRS derived using data from females of European ancestry. Our study markedly increases the population diversity in genetic studies for breast cancer and demonstrates the utility of PRS for risk prediction in females of African ancestry.

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AN - SCOPUS:85192400313

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JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

Genome-wide association analyses of breast cancer in women of African ancestry identify new susceptibility loci and improve risk prediction

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