- Tiankai Xie
- Josey C. Sorenson
- Logan G. Spector
Nathan Pankratz - R. Stephanie Huang
- Eiso Hiyama
- Jenny N. Poynter
- Gail E. Tomlinson
Carolina Armengol - Roland Kappler
- Michael E. Scheurer
- Eve Roman
- Aurora Castellano
- Michael A. Grotzer
- David S. Ziegler
- Saonli Basu
- Erin L. Marcotte
- Tianzhong Yang
Abstract
Hepatoblastoma (HB) is a rare embryonal liver tumor, with an increasing global incidence that underscores the need to understand its genetic etiology.
Utilizing the ancestry-matched expression quantitative loci data, we performed a HB transcriptome-wide association study (TWAS) on 4,539 Europeans, 1,047 Latinos, and 378 African Americans (∼1:10 case–control ratio). We conducted a meta-analysis of multiancestry transcriptome-wide analysis (METRO), 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.
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 8 genes among these 28, including OXER1 (meta-analysis P value = 7.34 × 10−6), FADS1 (P value = 4.01 × 10−6), and UGDH (P value = 5.29 × 10−8), 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 = 2.61 × 10−13, 3.62 × 10−3, and 1.95 × 10−9, respectively).