1. An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk
- Author
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Wu, Lang, Yang, Yaohua, Guo, Xingyi, Shu, Xiao Ou, Cai, Qiuyin, Shu, Xiang, Li, Bingshan, Tao, Ran, Wu, Chong, Nikas, Jason B., Sun, Yanfa, Zhu, Jingjing, Roobol, Monique J., Giles, Graham G., Brenner, Hermann, John, Esther M., Clements, Judith, Grindedal, Eli Marie, Park, Jong Y., Stanford, Janet L., Kote-Jarai, Zsofia, Haiman, Christopher A., Eeles, Rosalind A., Zheng, Wei, Long, Jirong, Henderson, Brian E., Schumacher, Fredrick R., Easton, Douglas, Benlloch, Sara, Olama, Ali Amin Al, Muir, Kenneth, Berndt, Sonja I., Conti, David V., Wiklund, Fredrik, Chanock, Stephen, Gapstur, Susan M., Stevens, Victoria L., Tangen, Catherine M., Batra, Jyotsna, Gronberg, Henrik, Pashayan, Nora, Schleutker, Johanna, Albanes, Demetrius, Weinstein, Stephanie, Wolk, Alicja, Nordestgaard, Børge G., Li, Bingshan [0000-0003-2129-168X], Wu, Chong [0000-0002-8400-1785], Nikas, Jason B [0000-0001-9703-0422], Roobol, Monique J [0000-0001-6967-1708], Giles, Graham G [0000-0003-4946-9099], Park, Jong Y [0000-0002-6384-6447], Eeles, Rosalind A [0000-0002-3698-6241], Zheng, Wei [0000-0003-1226-070X], Apollo - University of Cambridge Repository, Hunter, DJ, consortium, PRACTICAL, Consortium, CRUK, Consortium, BPC3, Consortium, CAPS, Consortium, PEGASUS, and Urology
- Subjects
0301 basic medicine ,Male ,General Physics and Astronomy ,02 engineering and technology ,VARIANTS ,urologic and male genital diseases ,DISEASE ,CRUK Consortium ,Prostate cancer ,BPC3 Consortium ,Risk Factors ,Epidemiology of cancer ,GWAS ,lcsh:Science ,Cancer genetics ,GENE-EXPRESSION ,Genetics ,Multidisciplinary ,Methylation ,021001 nanoscience & nanotechnology ,STATISTICS ,Multidisciplinary Sciences ,CpG site ,DNA methylation ,Science & Technology - Other Topics ,0210 nano-technology ,SUSCEPTIBILITY LOCI ,Science ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,PRACTICAL consortium ,03 medical and health sciences ,Cancer epidemiology ,SDG 3 - Good Health and Well-being ,REVEALS ,Genetic model ,medicine ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Gene ,Genetic Association Studies ,Genetic association ,Science & Technology ,Models, Genetic ,MORTALITY ,Prostatic Neoplasms ,General Chemistry ,DNA Methylation ,medicine.disease ,CAPS Consortium ,030104 developmental biology ,TISSUE ,ANTIGEN LEVEL ,Case-Control Studies ,lcsh:Q ,CpG Islands ,PEGASUS Consortium - Abstract
It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes., Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer.
- Published
- 2021
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