An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk.
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Date
2020-08-06Author
Wu, L
Yang, Y
Guo, X
Shu, X-O
Cai, Q
Shu, X
Li, B
Tao, R
Wu, C
Nikas, JB
Sun, Y
Zhu, J
Roobol, MJ
Giles, GG
Brenner, H
John, EM
Clements, J
Grindedal, EM
Park, JY
Stanford, JL
Kote-Jarai, Z
Haiman, CA
Eeles, RA
Zheng, W
Long, J
PRACTICAL consortium,
CRUK Consortium,
BPC3 Consortium,
CAPS Consortium,
PEGASUS Consortium,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
PRACTICAL consortium
CRUK Consortium
BPC3 Consortium
CAPS Consortium
PEGASUS Consortium
Humans
Prostatic Neoplasms
Genetic Predisposition to Disease
Risk Factors
Case-Control Studies
DNA Methylation
CpG Islands
Models, Genetic
Male
Genetic Association Studies
Biomarkers, Tumor
Research team
Oncogenetics
Language
eng
Date accepted
2020-06-28
License start date
2020-08-06
Citation
Nature communications, 2020, 11 (1), pp. 3905 - ?
Publisher
NATURE PUBLISHING GROUP
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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