Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Nat Commun. 2024 May 2;15(1):3718. doi: 10.1038/s41467-024-47650-5.
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.
非裔参与者在遗传学研究中代表性不足。在这里，我们对 150 名非裔女性参与者的正常乳腺组织进行了全转录组关联研究（TWAS），以鉴定潜在的乳腺癌易感基因。我们构建了遗传模型，使用基因组和转录组数据来预测基因表达水平、外显子连接和 3'UTR 可变多聚腺苷酸化，然后使用这些模型使用来自 18034 例病例和 22104 例对照的基因组数据进行关联分析。在 Bonferroni 校正的 P<0.05 水平下，我们确定了六个与乳腺癌风险相关的基因，包括四个以前未报道的基因（CTD-3080P12.3、EN1、LINC01956 和 NUP210L）。这些基因中的大多数与雌激素受体（ER）阴性或三阴性乳腺癌的风险相关性更强，而不是 ER 阳性乳腺癌。我们还在 P<0.05（单侧）水平上复制了之前 TWAS 中报告的 29 个基因的关联，进一步支持这些基因与乳腺癌风险的关联。我们的研究为乳腺癌的遗传基础提供了新的线索，并强调了在非裔人群中开展研究的价值。
