东亚人群肺癌基因的转录组与甲基化组关联研究
Transcriptome- and methylome-wide association studies prioritized lung cancer genes in East Asian populations
研究构建了东亚人群特异的基因表达与 DNA 甲基化预测模型，并在东亚肺癌 GWAS 中优先定位出 25 个基因和 42 个 CpG 位点与肺癌风险相关。模型分别基于 800 余人和 4,300 余人的全血数据训练，应用于南京医科大学（13,327 例病例、13,328 例对照）与 Biobank Japan（4,444 例病例、489,012 例对照）的肺癌 GWAS，发现阶段鉴定的位点中有 7 个基因和 32 个 CpG 位点得到重复验证。
来源：PLOS Genetics · journals.plos.org
by Xingjie Hao, Minghan Qu, Yi Jiang, Cheng Wang, Ziwei Zhu, Pinpin Long, Chaolong Wang, Hongxia Ma, Shanshan Cheng
The relationship between gene expression, DNA methylation, and lung cancer remains elusive in East Asian (EAS) populations. Transcriptome- and methylome-wide association studies (TWAS/MWAS) help uncover gene–trait associations by integrating multi-omics data, yet models trained mainly on European references limit cross-population generalizability. To address this, we developed EAS-specific gene expression and DNA methylation prediction models using whole-blood data from over 800 and 4,300 individuals, respectively. Applying these to lung cancer GWAS from Nanjing Medical University (13,327 cases; 13,328 controls) and Biobank Japan (4,444 cases; 489,012 controls), we identified 25 genes and 42 CpGs associated with lung cancer risk in the discovery stage, with seven genes and 32 CpGs replicated. Three novel genes outside known GWAS loci—RP11-57K17.1 (6q22.31), RP11-313J2.1 (10q11.21), and BMS1P2 (10q11.22)—were identified. In addition, Mendelian randomization analyses suggested that methylation-mediated downregulation of RP11-147L13.11 can reduce lung cancer risk. Our study reveals new susceptibility genes and offers insights into genetic-epigenetic regulatory mechanisms in lung cancer among EAS populations.