TY - JOUR
T1 - An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk
AU - Wu, Lang
AU - Yang, Yaohua
AU - Guo, Xingyi
AU - Shu, Xiao Ou
AU - Cai, Qiuyin
AU - Shu, Xiang
AU - Li, Bingshan
AU - Tao, Ran
AU - Wu, Chong
AU - Nikas, Jason B.
AU - Batra, Jyotsna
AU - Long, Jirong
AU - The PRACTICAL consortium
AU - CRUK Consortium
AU - BPC3 Consortium
AU - CAPS Consortium
AU - PEGASUS Consortium
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85089075304&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17673-9
DO - 10.1038/s41467-020-17673-9
M3 - Article
C2 - 32764609
AN - SCOPUS:85089075304
SN - 2041-1723
VL - 11
SP - 1
EP - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3905
ER -
