Multi-ancestry transcriptome-wide association study identifies candidate genes associated with hepatoblastoma
Menée à partir de données internationales portant sur des témoins et 5 964 patients atteints d'un hépatoblastome, cette étude d'association pangénomique identifie 8 gènes de susceptibilté à la maladie
Background: Hepatoblastoma (HB) is a rare embryonal liver tumor, with a rising global incidence that underscores the need to understand its genetic etiology.
Methods: Utilizing the ancestry-matched expression quantitative loci data, we performed a HB transcriptome-wide association study (TWAS) on 4539 Europeans, 1047 Latinos, and 378 African Americans (~1:10 cases control ratio). We conducted a multi-ancestry transcriptome-wide analysis (METRO) meta-analysis followed by METRO-EGGER sensitivity analysis and ancestry-specific gene set enrichment analyses. We further explored genes with additional evidence gathered from independent cohorts and databases.
Results: Across the three ancestries, the discovered genes shared the same effect direction across ancestries. A meta-analysis of the three ancestries identified 28 genes significantly associated with HB risk, and 15 were nominally significant for at least two ancestries. Our post-TWAS analyses highlighted eight genes among these 28, including OXER1 (meta-analysis p-value=7.3410-6), FADS1 (p-value=4.0110-6), and UGDH (p-value=5.2910-8), which were expressed in fetal liver hepatoblast cells and were differentially expressed in tumor and normal tissues in an independent Japanese HB study (p-values=2.6110-13, 3.6210-3 , and 1.9510-9, respectively).
Conclusions: We pinpoint eight potential genes associated with HB using data from an ongoing multi-ancestry genome-wide association study.
Impact: We conducted the largest HB TWAS to date, prompting further exploration of genes.
Cancer Epidemiology, Biomarkers & Prevention , résumé, 2025