Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes.
Date
2024-05-02ICR Author
Author
Ping, J
Jia, G
Cai, Q
Guo, X
Tao, R
Ambrosone, C
Huo, D
Ambs, S
Barnard, ME
Chen, Y
Garcia-Closas, M
Gu, J
Hu, JJ
John, EM
Li, CI
Nathanson, K
Nemesure, B
Olopade, OI
Pal, T
Press, MF
Sanderson, M
Sandler, DP
Yoshimatsu, T
Adejumo, PO
Ahearn, T
Brewster, AM
Hennis, AJM
Makumbi, T
Ndom, P
O'Brien, KM
Olshan, AF
Oluwasanu, MM
Reid, S
Yao, S
Butler, EN
Huang, M
Ntekim, A
Li, B
Troester, MA
Palmer, JR
Haiman, CA
Long, J
Zheng, W
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Adult
Aged
Female
Humans
Middle Aged
Black People
Breast Neoplasms
Case-Control Studies
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Genetic Predisposition to Disease
Genome-Wide Association Study
Polymorphism, Single Nucleotide
Receptors, Estrogen
Transcriptome
Black or African American
United States
Research team
Integrative Cancer Epidem
Language
eng
Date accepted
2024-04-08
License start date
2024-05-02
Citation
Nature Communications, 2024, 15 (1), pp. 3718 -
Publisher
NATURE PORTFOLIO