Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk Journal Article
| Authors: | Yang, Y.; Chen, Y.; Xu, S.; Guo, X.; Jia, G.; Ping, J.; Shu, X.; Zhao, T.; Yuan, F.; Wang, G.; Xie, Y.; Ci, H.; Liu, H.; Qi, Y.; Liu, Y.; Liu, D.; Li, W.; Ye, F.; Shu, X. O.; Zheng, W.; Li, L.; Cai, Q.; Long, J. |
| Article Title: | Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk |
| Abstract: | The relationship between tissue-specific DNA methylation and cancer risk remains inadequately elucidated. Leveraging resources from the Genotype-Tissue Expression consortium, here we develop genetic models to predict DNA methylation at CpG sites across the genome for seven tissues and apply these models to genome-wide association study data of corresponding cancers, namely breast, colorectal, renal cell, lung, ovarian, prostate, and testicular germ cell cancers. At Bonferroni-corrected P < 0.05, we identify 4248 CpGs that are significantly associated with cancer risk, of which 95.4% (4052) are specific to a particular cancer type. Notably, 92 CpGs within 55 putative novel loci retain significant associations with cancer risk after conditioning on proximal signals identified by genome-wide association studies. Integrative multi-omics analyses reveal 854 CpG-gene-cancer trios, suggesting that DNA methylation at 309 distinct CpGs might influence cancer risk through regulating the expression of 205 unique cis-genes. These findings substantially advance our understanding of the interplay between genetics, epigenetics, and gene expression in cancer etiology. © The Author(s) 2024. |
| Keywords: | methylation; genetics; neoplasm; neoplasms; genetic predisposition to disease; gene expression; germ cell; genotype; genome-wide association study; tumor marker; dna methylation; physiology; gene expression regulation; gene expression regulation, neoplastic; dna; cpg island; cpg islands; epigenesis, genetic; biomarker; organ specificity; testis tumor; testicular neoplasms; genomics; antibody specificity; neoplasms, germ cell and embryonal; health risk; genetic predisposition; genetic epigenesis; cancer; humans; human; male; female; testicular germ cell tumor; biomarkers, tumor; germ cell and embryonal neoplasms |
| Journal Title: | Nature Communications |
| Volume: | 15 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2024-07-18 |
| Start Page: | 6071 |
| Language: | English |
| DOI: | 10.1038/s41467-024-50404-y |
| PUBMED: | 39025880 |
| PROVIDER: | scopus |
| PMCID: | PMC11258330 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
