Transcriptome-wide association study of multiple myeloma identifies candidate susceptibility genes.

Area of Science:

• Genetics
• Oncology
• Bioinformatics

Background:

• Genome-wide association studies (GWAS) have identified 23 risk regions for multiple myeloma (MM), but the underlying causal genes remain largely unknown.
• Understanding these genetic underpinnings is crucial for deciphering MM pathogenesis.

Purpose of the Study:

• To identify candidate causal genes at known multiple myeloma risk regions using a multi-tissue transcriptome-wide association study (TWAS).
• To discover novel genetic regions associated with multiple myeloma risk.

Main Methods:

• Integrated genome-wide association study (GWAS) data from 7,319 multiple myeloma cases and 234,385 controls with Genotype-Tissue Expression (GTEx) Project data from 48 tissues.
• Employed transcriptome-wide association study (TWAS) to predict gene expression and identify associations with multiple myeloma risk.

Main Results:

• Identified 108 genes at 13 independent regions associated with multiple myeloma risk, all located within 1 Mb of known GWAS risk variants.
• Discovered 94 novel candidate genes in eight regions not previously implicated in multiple myeloma risk.
• Highlighted genes with plausible roles in multiple myeloma biology, including several APOBEC3 family members.

Conclusions:

• Leveraging multi-tissue expression data in TWAS is valuable for identifying genes underlying GWAS associations and understanding disease mechanisms.
• The identified genes provide a foundation for further research into multiple myeloma tumorigenesis and potential therapeutic strategies.
• Several identified genes, including APOBEC3 family members, warrant further investigation due to their potential roles in multiple myeloma and other cancers.