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

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

doi:10.1038/s41467-020-17673-9

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

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. StanfordZsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles, Wei Zheng, Jirong Long, The PRACTICAL consortium, CRUK Consortium, BPC3 Consortium, CAPS Consortium, PEGASUS Consortium

Research output: Contribution to journal › Article › Research › peer-review

3 Citations (Scopus)

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	https://doi.org/10.1038/s41467-020-17673-9
Publication status	Published - 6 Aug 2020
Externally published	Yes

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Wu, L., Yang, Y., Guo, X., Shu, X. O., Cai, Q., Shu, X., Li, B., Tao, R., Wu, C., Nikas, J. B., Sun, Y., Zhu, J., Roobol, M. J., Giles, G. G., Brenner, H., John, E. M., Clements, J., Grindedal, E. M., Park, J. Y., ... PEGASUS Consortium (2020). An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk. Nature Communications, 11(1), [3905]. https://doi.org/10.1038/s41467-020-17673-9

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. / An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk. In: Nature Communications. 2020 ; Vol. 11, No. 1.

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

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.",

author = "Lang Wu and Yaohua Yang and Xingyi Guo and Shu, {Xiao Ou} and Qiuyin Cai and Xiang Shu and Bingshan Li and Ran Tao and Chong Wu and Nikas, {Jason B.} and Yanfa Sun and Jingjing Zhu and Roobol, {Monique J.} and Giles, {Graham G.} and Hermann Brenner and John, {Esther M.} and Judith Clements and Grindedal, {Eli Marie} and Park, {Jong Y.} and Stanford, {Janet L.} and Zsofia Kote-Jarai and Haiman, {Christopher A.} and Eeles, {Rosalind A.} and Wei Zheng and Jirong Long and Henderson, {Brian E.} and Schumacher, {Fredrick R.} and Douglas Easton and Sara Benlloch and Olama, {Ali Amin Al} and Kenneth Muir and Berndt, {Sonja I.} and Conti, {David V.} and Fredrik Wiklund and Stephen Chanock and Gapstur, {Susan M.} and Stevens, {Victoria L.} and Tangen, {Catherine M.} and Jyotsna Batra and Henrik Gronberg and Nora Pashayan and Johanna Schleutker and Demetrius Albanes and Stephanie Weinstein and Alicja Wolk and Catharine West and Lorelei Mucci and G{\'e}raldine Cancel-Tassin and Stella Koutros and Sorensen, {Karina Dalsgaard} and Neal, {David E.} and Hamdy, {Freddie C.} and Donovan, {Jenny L.} and Travis, {Ruth C.} and Hamilton, {Robert J.} and Ingles, {Sue Ann} and Rosenstein, {Barry S.} and Lu, {Yong Jie} and Kibel, {Adam S.} and Ana Vega and Manolis Kogevinas and Penney, {Kathryn L.} and Cezary Cybulski and Nordestgaard, {B{\o}rge G.} and Christiane Maier and Jeri Kim and Teixeira, {Manuel R.} and Neuhausen, {Susan L.} and {De Ruyck}, Kim and Azad Razack and Newcomb, {Lisa F.} and Marija Gamulin and Radka Kaneva and Nawaid Usmani and Frank Claessens and Townsend, {Paul A.} and Dominguez, {Manuela Gago} and Florence Menegaux and Khaw, {Kay Tee} and Lisa Cannon-Albright and Hardev Pandha and Thibodeau, {Stephen N.} and Hunter, {David J.} and Blot, {William J.} and Elio Riboli and Catharine West and Neal, {David E.} and Hamdy, {Freddie C.} and Donovan, {Jenny L.} and Travis, {Ruth C.} and Elio Riboli and Henderson, {Brian E.} and Schumacher, {Fredrick R.} and Berndt, {Sonja I.} and Stephen Chanock and Gapstur, {Susan M.} and Stevens, {Victoria L.} and Demetrius Albanes and Stephanie Weinstein and Lorelei Mucci and Stella Koutros and Travis, {Ruth C.} and Penney, {Kathryn L.} and Hunter, {David J.} and Elio Riboli and Fredrik Wiklund and Henrik Gronberg and Berndt, {Sonja I.} and Stephen Chanock and Demetrius Albanes and Stephanie Weinstein and Stella Koutros and {The PRACTICAL consortium} and {CRUK Consortium} and {BPC3 Consortium} and {CAPS Consortium} and {PEGASUS Consortium}",

year = "2020",

month = aug,

day = "6",

doi = "10.1038/s41467-020-17673-9",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

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Wu, L, Yang, Y, Guo, X, Shu, XO, 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, The PRACTICAL consortium, CRUK Consortium, BPC3 Consortium, CAPS Consortium & PEGASUS Consortium 2020, 'An integrative multi-omics analysis to identify candidate DNA methylation biomarkers related to prostate cancer risk', Nature Communications, vol. 11, no. 1, 3905. https://doi.org/10.1038/s41467-020-17673-9

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.

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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 -