Transcriptome- and methylome-wide association studies prioritized lung cancer genes in East Asian populations.

EAS-specific TWAS/MWAS in whole-blood data linked 25 genes and 42 CpGs to lung cancer risk, with seven genes and 32 CpGs replicated across Nanjing Medical University and Biobank Japan.

• Why it matters: Cross-population transfer of multi-omics models is limited because most TWAS/MWAS training relies on European references, leaving gene expression and DNA methylation relationships unclear in East Asian populations.
• What they did: The study built EAS prediction models from whole blood (over 800 for expression; 4,300 for methylation), then tested them in lung cancer GWAS from Nanjing Medical University (13,327 cases; 13,328 controls) and Biobank Japan (4,444 cases; 489,012 controls).
• The result: It prioritized three novel genes outside known GWAS loci—RP11-57K17.1, RP11-313J2.1, and BMS1P2—and Mendelian randomization suggested methylation-mediated downregulation of RP11-147L13.11 may reduce lung cancer risk.

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