Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.
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Peer-reviewed
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Authors
Adedokun, Babatunde
Du, Zhaohui
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.
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Keywords
Black People, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Introns, Polymorphism, Single Nucleotide, Quantitative Trait Loci, White People
Journal Title
Nat Commun
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Journal ISSN
2041-1723
2041-1723
2041-1723
Volume Title
12
Publisher
Springer Science and Business Media LLC
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All rights reserved
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (A16563)
Cancer Research UK (A10118)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (A16563)
Cancer Research UK (A10118)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
The ROOT Consortium was supported by National Cancer Institute grants R01-CA142996, R01-CA89085, R01-CA228198, and P20-CA233307. DH and OIO were also supported by Breast Cancer Research Foundation. DH and GG were also partially supported by the National Cancer Institute (R03-CA227357 and R01-CA242929).
AABC was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to CAH [W81XWH-08-1-0383] and the Norris Foundation. Each of the participating AABC studies was supported by the following grants: MEC (National Institutes of Health grants R01-CA63464 and R37-CA54281); CARE (National Institute for Child Health and Development grant NO1-HD-3-3175, K05 CA136967); WCHS (U.S. Army Medical Research and Material Command (USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health grant R01-CA100598, and the Breast Cancer Research Foundation; SFBCS (National Institutes of Health grant R01-CA077305 and United States Army Medical Research Program grant DAMD17-96-6071); NC-BCFR (National Institutes of Health grant U01-CA069417); CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility National Institute of Environmental Health Sciences, National Institutes of Health, grant number P30-ES10126); PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health); NBHS (National Institutes of Health grant R01-CA100374). The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. MP was supported by Breast Cancer Research Foundation, Tower Cancer Research Foundation, and a gift from Dr. Richard Balch.
AMBER was supported by the National Cancer Institute grants P01-CA151135, R01-CA098663, R01-CA058420, UM1-CA164974, R01-CA100598, P50-CA58223, and the University Cancer Research Fund of North Carolina. JRP was supported by the Susan G. Komen Foundation and the Karin Grunebaum Foundation. Pathology data were obtained from numerous state cancer registries (Arizona, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Georgia, Hawaii, Illinois, Indiana, Kentucky, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, North Carolina, Oklahoma, Pennsylvania, South Carolina, Tennessee, Texas, Virginia). The results reported do not necessarily represent their views or the views of the National Institutes of Health.
BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union's Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST respectively), and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. The Sister Study was funded by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES044005).
GBHS authors acknowledge the research contributions of the Cancer Genomics Research Laboratory for their expertise, execution, and support of this research in the areas of project planning, wet laboratory processing of specimens, and bioinformatics analysis of generated data. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under NCI Contract No. 75N910D00024. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.