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.
Original language | English |
---|---|
Article number | 3905 |
Number of pages | 11 |
Journal | Nature Communications |
Volume | 11 |
Issue number | 1 |
DOIs | |
Publication status | Published - 6 Aug 2020 |
Externally published | Yes |
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An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk. / 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; The PRACTICAL consortium; CRUK Consortium; BPC3 Consortium; CAPS Consortium; PEGASUS Consortium.
In: Nature Communications, Vol. 11, No. 1, 3905, 06.08.2020.Research output: Contribution to journal › Article › Research › peer-review
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 - Sun, Yanfa
AU - Zhu, Jingjing
AU - Roobol, Monique J.
AU - Giles, Graham G.
AU - Brenner, Hermann
AU - John, Esther M.
AU - Clements, Judith
AU - Grindedal, Eli Marie
AU - Park, Jong Y.
AU - Stanford, Janet L.
AU - Kote-Jarai, Zsofia
AU - Haiman, Christopher A.
AU - Eeles, Rosalind A.
AU - Zheng, Wei
AU - Long, Jirong
AU - Henderson, Brian E.
AU - Schumacher, Fredrick R.
AU - Easton, Douglas
AU - Benlloch, Sara
AU - Olama, Ali Amin Al
AU - Muir, Kenneth
AU - Berndt, Sonja I.
AU - Conti, David V.
AU - Wiklund, Fredrik
AU - Chanock, Stephen
AU - Gapstur, Susan M.
AU - Stevens, Victoria L.
AU - Tangen, Catherine M.
AU - Batra, Jyotsna
AU - Gronberg, Henrik
AU - Pashayan, Nora
AU - Schleutker, Johanna
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Wolk, Alicja
AU - West, Catharine
AU - Mucci, Lorelei
AU - Cancel-Tassin, Géraldine
AU - Koutros, Stella
AU - Sorensen, Karina Dalsgaard
AU - Neal, David E.
AU - Hamdy, Freddie C.
AU - Donovan, Jenny L.
AU - Travis, Ruth C.
AU - Hamilton, Robert J.
AU - Ingles, Sue Ann
AU - Rosenstein, Barry S.
AU - Lu, Yong Jie
AU - Kibel, Adam S.
AU - Vega, Ana
AU - Kogevinas, Manolis
AU - Penney, Kathryn L.
AU - Cybulski, Cezary
AU - Nordestgaard, Børge G.
AU - Maier, Christiane
AU - Kim, Jeri
AU - Teixeira, Manuel R.
AU - Neuhausen, Susan L.
AU - De Ruyck, Kim
AU - Razack, Azad
AU - Newcomb, Lisa F.
AU - Gamulin, Marija
AU - Kaneva, Radka
AU - Usmani, Nawaid
AU - Claessens, Frank
AU - Townsend, Paul A.
AU - Dominguez, Manuela Gago
AU - Menegaux, Florence
AU - Khaw, Kay Tee
AU - Cannon-Albright, Lisa
AU - Pandha, Hardev
AU - Thibodeau, Stephen N.
AU - Hunter, David J.
AU - Blot, William J.
AU - Riboli, Elio
AU - West, Catharine
AU - Neal, David E.
AU - Hamdy, Freddie C.
AU - Donovan, Jenny L.
AU - Travis, Ruth C.
AU - Riboli, Elio
AU - Henderson, Brian E.
AU - Schumacher, Fredrick R.
AU - Berndt, Sonja I.
AU - Chanock, Stephen
AU - Gapstur, Susan M.
AU - Stevens, Victoria L.
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Mucci, Lorelei
AU - Koutros, Stella
AU - Travis, Ruth C.
AU - Penney, Kathryn L.
AU - Hunter, David J.
AU - Riboli, Elio
AU - Wiklund, Fredrik
AU - Gronberg, Henrik
AU - Berndt, Sonja I.
AU - Chanock, Stephen
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Koutros, Stella
AU - The PRACTICAL consortium
AU - CRUK Consortium
AU - BPC3 Consortium
AU - CAPS Consortium
AU - PEGASUS Consortium
PY - 2020/8/6
Y1 - 2020/8/6
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
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 3905
ER -