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An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk

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 ris...

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Main Authors: Wu, Lang (Author) , Yang, Yaohua (Author) , Guo, Xingyi (Author) , Shu, Xiao-Ou (Author) , Cai, Qiuyin (Author) , Shu, Xiang (Author) , Li, Bingshan (Author) , Tao, Ran (Author) , Wu, Chong (Author) , Nikas, Jason B. (Author) , Sun, Yanfa (Author) , Zhu, Jingjing (Author) , Roobol, Monique J. (Author) , Giles, Graham G. (Author) , Brenner, Hermann (Author) , John, Esther M. (Author) , Clements, Judith (Author) , Grindedal, Eli Marie (Author) , Park, Jong Y. (Author) , Stanford, Janet L. (Author) , Kote-Jarai, Zsofia (Author) , Haiman, Christopher A. (Author) , Eeles, Rosalind A. (Author) , Zheng, Wei (Author) , Long, Jirong (Author)
Format: Article (Journal)
Language:English
Published: 06 August 2020
In: Nature Communications
Year: 2020, Volume: 11
ISSN:2041-1723
DOI:10.1038/s41467-020-17673-9
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-020-17673-9
Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-020-17673-9
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Author Notes:Lang Wu, Yaohua Yang, Xingyi Guo, Xiao-Ou Shu, Qiuyin Cai, Xiang Shu, Bingshan Li, Ran Tao, Chong Wu, Jason B. Nikas, Yanfa Sun, Jingjing Zhu, Monique J. Roobol, Graham G. Giles, Hermann Brenner, Esther M. John, Judith Clements, Eli Marie Grindedal, Jong Y. Park, Janet L. Stanford, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles, Wei Zheng, Jirong Long, The PRACTICAL consortium, CRUK Consortium, BPC3 Consortium,CAPS Consortium & PEGASUS Consortium
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Summary: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.
Item Description:Gesehen am 23.09.2020
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-020-17673-9

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