Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics
Document Type
Article
Publication Date
12-1-2022
Abstract
By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome-and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were asso-ciated with breast cancer risk at a p < 5.0 3 10-8 and a Bonferroni-corrected p < 4.6 3 10-6, respectively. Of them, 32 loci and 15 genes showed a significantly different association between ER-positive and ER-negative breast cancer after Bonferroni correction. Significant ancestral differences in risk variant allele frequencies and their association strengths with breast cancer risk were identified. Of the sig-nificant associations identified in this study, 17 loci and 14 genes are located 1Mb away from any of the previously reported breast cancer risk variants. Pathways analyses including 221 putative risk genes identified multiple signaling pathways that may play a significant role in the development of breast cancer. Our study provides a comprehensive understanding of and new biological insights into the genetics of this common malignancy.
Keywords
SUSCEPTIBILITY LOCI, RISK, TUMORIGENESIS
Divisions
surgerydept
Funders
United States Department of Health & Human Services National Institutes of Health (NIH) - USA,United States Department of Defense,Ingram Professor and Anne Potter Wilson Chair and Research Reward funds,Vanderbilt-Ingram Cancer Center,Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT) Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (KAKENHI)
Publication Title
AMERICAN JOURNAL OF HUMAN GENETICS
Volume
109
Issue
12
Publisher
CELL PRESS
Publisher Location
50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA