Using genome and transcriptome data from African-ancestry female participants to identify putative breast cancer susceptibility genes.
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ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2024-05-02
Date Accepted
2024-04-08
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.
Citation
Nature Communications, 2024, 15 (1), pp. 3718 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Integrative Cancer Epidem