التفاصيل البيبلوغرافية
| العنوان: |
Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry |
| المؤلفون: |
Mueller, S.H., Augustinsson, A., Olsson, H., Kuchenbaecker, Karoline B. |
| المصدر: |
Genome Medicine EpiHealth: Epidemiology for Health. 15(1) |
| مصطلحات موضوعية: |
Breast cancer susceptibility, Diverse ancestry, Gene regulation, Genome-wide association study, Rare variants, African, ancestry group, Article, Asian, boredom susceptibility, breast cancer, cancer prognosis, CBLB gene, cohort analysis, controlled study, ESR1 gene, European, FGFR2 gene, FMNL3 gene, gene base aggregation, gene expression level, gene structure, genetic association, genetic association study, genetic code, genetic variability, Hispanic, human, human cell, human tissue, LSP1 gene, major clinical study, MAP3K1 gene, meta analysis (topic), South and Central America, SRGAP2C gene, statistical significance, tumor-related gene, Black person, breast tumor, female, genetic predisposition, genetic screening, genetics, genome-wide association study, meta analysis, procedures, single nucleotide polymorphism, FMNL3 protein, methenamine, Black People, Breast Neoplasms, Female, Formins, Genetic Predisposition to Disease, Genetic Testing, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Medicin och hälsovetenskap, Medicinska och farmaceutiska grundvetenskaper, Medicinsk genetik, Medical and Health Sciences, Basic Medicine, Medical Genetics, Klinisk medicin, Cancer och onkologi, Clinical Medicine, Cancer and Oncology |
| الوصف: |
Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10−6) and AC058822.1 (P = 1.47 × 10−4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10−5), demonstrating the importance of diversifying study cohorts. © 2023, The Author(s). |
| الوصول الحر: |
https://lup.lub.lu.se/record/03b290d6-d650-490a-9e52-2fcb867a25b3Test
http://dx.doi.org/10.1186/s13073-022-01152-5Test |
| قاعدة البيانات: |
SwePub |
