Nature Communications (May 2024)
Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes
- Jie Ping,
- Guochong Jia,
- Qiuyin Cai,
- Xingyi Guo,
- Ran Tao,
- Christine Ambrosone,
- Dezheng Huo,
- Stefan Ambs,
- Mollie E. Barnard,
- Yu Chen,
- Montserrat Garcia-Closas,
- Jian Gu,
- Jennifer J. Hu,
- Esther M. John,
- Christopher I. Li,
- Katherine Nathanson,
- Barbara Nemesure,
- Olufunmilayo I. Olopade,
- Tuya Pal,
- Michael F. Press,
- Maureen Sanderson,
- Dale P. Sandler,
- Toshio Yoshimatsu,
- 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,
- Song Yao,
- Ebonee N. Butler,
- Maosheng Huang,
- Atara Ntekim,
- Bingshan Li,
- Melissa A. Troester,
- Julie R. Palmer,
- Christopher A. Haiman,
- Jirong Long,
- Wei Zheng
Affiliations
- Jie Ping
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Guochong Jia
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Qiuyin Cai
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Xingyi Guo
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Ran Tao
- Department of Biostatistics, Vanderbilt University Medical Center
- Christine Ambrosone
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets
- Dezheng Huo
- Department of Public Health Sciences, The University of Chicago
- Stefan Ambs
- Laboratory of Human Carcinogenesis, Center of Cancer Research, National Cancer Institute, National Institutes of Health
- Mollie E. Barnard
- Slone Epidemiology Center, Boston University
- Yu Chen
- Division of Epidemiology, Department of Population Health, NYU Grossman School of Medicine
- Montserrat Garcia-Closas
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Jian Gu
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center
- Jennifer J. Hu
- Department of Public Health Sciences, University of Miami School of Medicine
- Esther M. John
- Departments of Epidemiology & Population Health and of Medicine, Stanford University School of Medicine
- Christopher I. Li
- Division of Public Health Sciences, Fred Hutchinson Cancer Center
- Katherine Nathanson
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania
- Barbara Nemesure
- Department of Family, Population and Preventive Medicine, Renaissance School of Medicine, Stony Brook University
- Olufunmilayo I. Olopade
- Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago
- Tuya Pal
- Division of Genetic Medicine, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Michael F. Press
- Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California
- Maureen Sanderson
- Department of Family and Community Medicine, Meharry Medical College
- Dale P. Sandler
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health
- Toshio Yoshimatsu
- Department of Public Health Sciences, The University of Chicago
- Prisca O. Adejumo
- Department of Nursing, College of Medicine, University of Ibadan
- Thomas Ahearn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute
- Abenaa M. Brewster
- Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center
- Anselm J. M. Hennis
- George Alleyne Chronic Disease Research Centre, University of the West Indies
- Timothy Makumbi
- Department of Surgery, Mulago Hospital
- Paul Ndom
- Yaounde General Hospital
- Katie M. O’Brien
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health
- Andrew F. Olshan
- Department of Epidemiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Mojisola M. Oluwasanu
- Department of Health Promotion and Education, College of Medicine, University of Ibadan
- Sonya Reid
- Division of Hematology and Oncology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Song Yao
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Elm & Carlton Streets
- Ebonee N. Butler
- Department of Epidemiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Maosheng Huang
- Department of Epidemiology, The University of Texas MD Anderson Cancer Center
- Atara Ntekim
- Department of Radiation Oncology, College of Medicine, University of Ibadan
- Bingshan Li
- Department of Molecular Physiology & Biophysics, Vanderbilt Genetics Institute, Vanderbilt University
- Melissa A. Troester
- Department of Epidemiology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
- Julie R. Palmer
- Slone Epidemiology Center, Boston University
- Christopher A. Haiman
- Department of Preventive Medicine, Keck School of Medicine of USC
- Jirong Long
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center
- DOI
- https://doi.org/10.1038/s41467-024-47650-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 8
Abstract
Abstract African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3′ UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls. At Bonferroni-corrected P < 0.05, we identified six genes associated with breast cancer risk, including four genes not previously reported (CTD-3080P12.3, EN1, LINC01956 and NUP210L). Most of these genes showed a stronger association with risk of estrogen-receptor (ER) negative or triple-negative than ER-positive breast cancer. We also replicated the associations with 29 genes reported in previous TWAS at P < 0.05 (one-sided), providing further support for an association of these genes with breast cancer risk. Our study sheds new light on the genetic basis of breast cancer and highlights the value of conducting research in AA populations.
