Multiancestry Transcriptome-Wide Association Study Identifies Candidate Genes Associated with Hepatoblastoma

Area of Science:

• Genetics
• Oncology
• Molecular Biology

Background:

• Hepatoblastoma (HB) is a rare embryonic liver tumor with rising global incidence.
• Understanding the genetic factors contributing to HB is crucial due to its increasing prevalence.

Purpose of the Study:

• To conduct the largest transcriptome-wide association study (TWAS) for hepatoblastoma (HB) to date.
• To identify novel genetic risk factors associated with HB across diverse ancestries.

Main Methods:

• A meta-analysis of multiancestry TWAS (METRO) was performed on European, Latino, and African American cohorts.
• Expression quantitative loci (eQTL) data and independent cohorts were utilized for gene exploration.
• Ancestry-specific gene set enrichment analyses and METRO-Egger sensitivity analyses were conducted.

Main Results:

• A meta-analysis identified 28 genes significantly associated with HB risk, with 15 showing nominal significance in at least two ancestries.
• Eight key genes, including OXER1, FADS1, and UGDH, were highlighted.
• These identified genes were expressed in fetal liver cells and showed differential expression in HB tumor tissues.

Conclusions:

• Eight potential genes associated with HB risk were pinpointed using multiancestry genome-wide association study data.
• This study represents the largest HB TWAS, providing a foundation for further genetic investigations into HB etiology.