Cross-Ancestry GWAS Meta-Analysis Identifies Six Breast Cancer Loci in African and European Ancestry Women

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Citation

Adedokun, Babatunde; Du, Zhaohui; Gao, Guimin; Ahearn, Thomas U.; Lunetta, Kathryn L.; Zirpoli, Gary R.; Figueroa, Jonine; John, Esther M.; Bernstein, Leslie; & Zheng, Wei, et al. (2021). Cross-Ancestry GWAS Meta-Analysis Identifies Six Breast Cancer Loci in African and European Ancestry Women. Nature Communications, 12(1), 4198. PMCID: PMC8263739

Abstract

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium. The approach identifies four loci for overall breast cancer risk [1p13.3, 5q31.1, 15q24 (two independent signals), and 15q26.3] and two loci for estrogen receptor-negative disease (1q41 and 7q11.23) at genome-wide significance. Four of the index single nucleotide polymorphisms (SNPs) lie within introns of genes (KCNK2, C5orf56, SCAMP2, and SIN3A) and the other index SNPs are located close to GSTM4, AMPD2, CASTOR2, and RP11-168G16.2. Here we present risk loci with consistent direction of associations in African and European descendants. The study suggests that replication across multiple ancestry populations can help improve the understanding of breast cancer genetics and identify causal variants.

URL

http://dx.doi.org/10.1038/s41467-021-24327-x

Reference Type

Journal Article

Year Published

2021

Journal Title

Nature Communications

Author(s)

Adedokun, Babatunde
Du, Zhaohui
Gao, Guimin
Ahearn, Thomas U.
Lunetta, Kathryn L.
Zirpoli, Gary R.
Figueroa, Jonine
John, Esther M.
Bernstein, Leslie
Zheng, Wei
Hu, Jennifer J.
Ziegler, Regina G.
Nyante, Sarah J.
Bandera, Elisa V.
Ingles, Sue A.
Press, Michael F.
Deming-Halverson, Sandra L.
Rodriguez-Gil, Jorge L.
Yao, Song
Ogundiran, Temidayo O.
Ojengbede, Oladosu
Blot, William J.
Troester, Melissa A.
Nathanson, Katherine L.
Hennis, Anselm J.
Nemesure, Barbara
Ambs, Stefan
Fiorica, Peter N.
Sucheston-Campbell, Lara E.
Bensen, Jeannette T.
Kushi, Lawerence H.
Torres-Mejia, Gabriela
Hu, Donglei
Fejerman, Laura
Bolla, Manjeet K.
Dennis, Joe
Dunning, Alison M.
Easton, Douglas F.
Michailidou, Kyriaki
Pharoah, Paul D. P.
Wang, Qin
Sandler, Dale P.
Taylor, Jack A.
O'Brien, Katie M.
Kitahara, Cari M.
Falusi, Adeyinka G.
Babalola, Chinedum
Yarney, Joel
Awuah, Baffour
Addai Wiafe, Beatrice
Chanock, Stephen J.
Olshan, Andrew F.
Ambrosone, Christine B.
Conti, David V.
Ziv, Elad
Olopade, Olufunmilayo I.
Garcia-Closas, M.
Palmer, Julie R.
Haiman, Christopher A.
Huo, Dezheng

Article Type

Regular

PMCID

PMC8263739

Race/Ethnicity

African Ancestry
European Ancestry

Sex/Gender

Women

ORCiD

Olshan - 0000-0001-9115-5128