{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:00:16Z","timestamp":1790600416463,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Breast cancer genome-wide association studies (GWAS) have identified more than 200 susceptibility loci, but most studies are dominated by European and East Asian populations.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We analyzed breast cancer GWAS summary statistics from African (AFR), East Asian (EAS), European (EUR), and Hispanic\/Latina (H\/L) samples (159,297 cases and 212,102 controls). We estimated logit-scale SNP-based heritability, polygenicity, and cross-ancestry genetic correlation, partitioned heritability across functional annotations, and integrated GWAS results with the Tabula Sapiens single-cell atlas using scDRS+.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The logit-scale heritability of breast cancer ranged from h2=0.47 (SE\u2009=\u20090.07) in EAS to AFR h2=0.61 (SE\u2009=\u20090.10), with no significant differences across ancestries (p\u2009=\u20090.63). The model-implied number of non-null susceptibility SNPs in the sparse normal-mixture effect-size model also varied from 4,446 (SE\u2009=\u20093,100) in EAS to 8,308 (SE\u2009=\u20092,751) in AFR, but differences were not significant across ancestries (p\u2009=\u20090.55). Cross-sample genetic correlations varied, with the strongest correlation between EUR and EAS (\u03c1=0.79, SE\u2009=\u20090.08) and weakest between AFR and H\/L (\u03c1=0.26, SE\u2009=\u20090.24). Regulatory annotations were enriched for breast cancer heritability across samples. Integration with single-cell expression profiles implicated ancestry-shared associations with innate immune, secretory epithelial, and stromal cell types.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n These results indicate substantial cross-ancestry sharing of breast cancer polygenic architecture, highlight a consistent contribution of regulatory variation, and identify convergent cellular contexts that motivate functional follow-up and inform expectations for the transferability and attainable performance of common-variant risk prediction across populations.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jncics\/pkag101","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T11:15:53Z","timestamp":1790334953000},"source":"Crossref","is-referenced-by-count":0,"title":["Genetic and cellular architecture of breast cancer risk across ancestries"],"prefix":"10.1093","author":[{"given":"James L","family":"Li","sequence":"first","affiliation":[{"name":"University of Chicago Department of Public Health Sciences, , Chicago, IL,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zanti","sequence":"additional","affiliation":[{"name":"The Cyprus Institute of Neurology and Genetics Department of Biostatistics, , Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Williams","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Om","family":"Jahagirdar","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochong","family":"Jia","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, , Nashville, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair","family":"Turcan","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University Ray and Stephanie Lane Computational Biology Department, School of Computer Science, , Pittsburgh, PA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Hu","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center Department of Biostatistics and Bioinformatics, , Buffalo, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Tristan","family":"Brandenburg","sequence":"additional","affiliation":[{"name":"University of the Witwatersrand Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, , Johannesburg,","place":["South Africa"]},{"name":"University of the Witwatersrand Strengthening Oncology Services Research Unit, Faculty of Health Sciences, , Johannesburg,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yan","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center Department of Biostatistics and Bioinformatics, , Buffalo, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weang-Kee","family":"Ho","sequence":"additional","affiliation":[{"name":"University of Nottingham Malaysia School of Mathematical Sciences, Faculty of Science and Engineering, , Semenyih, Selangor,","place":["Malaysia"]},{"name":"Cancer Research Malaysia , Subang Jaya, Selangor,","place":["Malaysia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingmei","family":"Li","sequence":"additional","affiliation":[{"name":"Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR) ,","place":["Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Patricio","family":"Miranda","sequence":"additional","affiliation":[{"name":"Pontificia Universidad Cat\u00f3lica de Chile Department of Nutrition, Diabetes and Metabolism, School of Medicine, , Santiago,","place":["Chile"]},{"name":"Pontificia Universidad Cat\u00f3lica de Chile PhD Program in Epidemiology, , Santiago,","place":["Chile"]},{"name":"Pontificia Universidad Cat\u00f3lica de Chile & Universidad de Chile Advanced Center for Chronic Diseases, , Santiago,","place":["Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Godbole","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-Alexia","family":"Dias","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health Department of Biostatistics, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Cambridge Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, , Cambridge,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"Dorling","sequence":"additional","affiliation":[{"name":"University of Cambridge Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, , Cambridge,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong Carl","family":"Chen","sequence":"additional","affiliation":[{"name":"University of the Witwatersrand Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, , Johannesburg,","place":["South Africa"]},{"name":"University of the Witwatersrand Strengthening Oncology Services Research Unit, Faculty of Health Sciences, , Johannesburg,","place":["South Africa"]},{"name":"National Health Laboratory Service National Cancer Registry, a Division of the National Institute for Communicable Diseases, , Johannesburg,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Boddicker","sequence":"additional","affiliation":[{"name":"Mayo Clinic Department of Quantitative Health Sciences, , Rochester, MN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Analytic and Translational Genetics Unit, , Boston, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Martin","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Analytic and Translational Genetics Unit, , Boston, MA,","place":["USA"]},{"name":"Harvard Medical School Department of Medicine, , Boston, MA,","place":["USA"]},{"name":"Broad Institute of MIT and Harvard Stanley Center for Psychiatric Research, , Cambridge, MA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Dora","family":"Zhang","sequence":"additional","affiliation":[{"name":"The University of Hong Kong Department of Statistics & Actuarial Science, School of Computing and Data Science, , Hong Kong SAR,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Dennis","sequence":"additional","affiliation":[{"name":"University of Cambridge Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, , Cambridge,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther M","family":"John","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine Departments of Epidemiology & Population Health and of Medicine (Oncology), , Stanford, CA,","place":["USA"]},{"name":"Stanford University School of Medicine Stanford Cancer Institute, , Stanford, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela","family":"Torres-Mejia","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Salud P\u00fablica , Cuernavaca,","place":["Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence H","family":"Kushi","sequence":"additional","affiliation":[{"name":"University of California UC Davis Genome Center, , Davis, Davis, CA,","place":["USA"]},{"name":"Kaiser Permanente Northern California Division of Research, , Oakland, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Weitzel","sequence":"additional","affiliation":[{"name":"University of Kansas Comprehensive Cancer Center Division of Precision Prevention, , Kansas City, KS,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L","family":"Neuhausen","sequence":"additional","affiliation":[{"name":"Beckman Research Institute of City of Hope Department of Population Sciences, , Duarte, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Carvajal-Carmona","sequence":"additional","affiliation":[{"name":"University of California at Davis Department of Biochemistry and Molecular Medicine, School of Medicine, , Davis, CA,","place":["USA"]},{"name":"University of California at Davis The Health Equity, Leadership, Science and Community Laboratory, Genome Center, , Davis, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Haiman","sequence":"additional","affiliation":[{"name":"University of Southern California Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, , Los Angeles, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elad","family":"Ziv","sequence":"additional","affiliation":[{"name":"University of California Division of General Internal Medicine, Department of Medicine, , San Francisco, San Francisco, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Fejerman","sequence":"additional","affiliation":[{"name":"University of California Davis Department of Public Health Sciences, , Davis, CA,","place":["USA"]},{"name":"University of California Davis Genome Center, , Davis, CA,","place":["USA"]},{"name":"University of California Davis UC Davis Comprehensive Cancer Center, , Davis, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, , Nashville, TN,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezheng","family":"Huo","sequence":"additional","affiliation":[{"name":"University of Chicago Department of Public Health Sciences, , Chicago, IL,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Easton","sequence":"additional","affiliation":[{"name":"University of Cambridge Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, , Cambridge,","place":["UK"]},{"name":"University of Cambridge Centre for Cancer Genetic Epidemiology, Department of Oncology, , Cambridge,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J","family":"Chanock","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilanjan","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Johns Hopkins University Department of Biostatistics, , Baltimore, MD,","place":["USA"]},{"name":"Johns Hopkins School of Medicine Department of Oncology, , Baltimore, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Kraft","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Montserrat","family":"Garcia-Closas","sequence":"additional","affiliation":[{"name":"The Institute of Cancer Research and Imperial College London Cancer Epidemiology and Prevention Research Unit, , London,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy S W","family":"Wong","sequence":"additional","affiliation":[{"name":"National Institutes of Health Division of Cancer Epidemiology and Genetics, National Cancer Institute, , Bethesda, MD,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriaki","family":"Michailidou","sequence":"additional","affiliation":[{"name":"The Cyprus Institute of Neurology and Genetics Department of Biostatistics, , Nicosia, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Zhu","sequence":"additional","affiliation":[{"name":"Roswell Park Comprehensive Cancer Center Department of Biostatistics and Bioinformatics, , Buffalo, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin Jinye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Carnegie Mellon University Ray and Stephanie Lane Computational Biology Department, School of Computer Science, , Pittsburgh, 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