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Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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Harvard

Amin Al Olama, A, Dadaev, T, Hazelett, DJ, Li, Q, Leongamornlert, D, Saunders, EJ, Stephens, S, Cieza-Borrella, C, Whitmore, I, Benlloch Garcia, S, Giles, GG, Southey, MC, Fitzgerald, L, Gronberg, H, Wiklund, F, Aly, M, Henderson, BE, Schumacher, F, Haiman, CA, Schleutker, J, Wahlfors, T, Tammela, TL, Nordestgaard, BG, Key, TJ, Travis, RC, Neal, DE, Donovan, JL, Hamdy, FC, Pharoah, P, Pashayan, N, Khaw, K-T, Stanford, JL, Thibodeau, SN, Mcdonnell, SK, Schaid, DJ, Maier, C, Vogel, W, Luedeke, M, Herkommer, K, Kibel, AS, Cybulski, C, Wokołorczyk, D, Kluzniak, W, Cannon-Albright, L, Brenner, H, Butterbach, K, Arndt, V, Park, JY, The PRACTICAL Consortium(Peter Iversen, Martin Andreas Røder, members), Iversen, P (red.) & Røder, MA (red.) 2015, 'Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans' Human Molecular Genetics, bind 24, nr. 19, s. 5589-602. https://doi.org/10.1093/hmg/ddv203

APA

CBE

Amin Al Olama A, Dadaev T, Hazelett DJ, Li Q, Leongamornlert D, Saunders EJ, Stephens S, Cieza-Borrella C, Whitmore I, Benlloch Garcia S, Giles GG, Southey MC, Fitzgerald L, Gronberg H, Wiklund F, Aly M, Henderson BE, Schumacher F, Haiman CA, Schleutker J, Wahlfors T, Tammela TL, Nordestgaard BG, Key TJ, Travis RC, Neal DE, Donovan JL, Hamdy FC, Pharoah P, Pashayan N, Khaw K-T, Stanford JL, Thibodeau SN, Mcdonnell SK, Schaid DJ, Maier C, Vogel W, Luedeke M, Herkommer K, Kibel AS, Cybulski C, Wokołorczyk D, Kluzniak W, Cannon-Albright L, Brenner H, Butterbach K, Arndt V, Park JY, The PRACTICAL Consortium(Peter Iversen, Martin Andreas Røder, members), Iversen P, Røder MA, red. 2015. Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. Human Molecular Genetics. 24(19):5589-602. https://doi.org/10.1093/hmg/ddv203

MLA

Vancouver

Author

Amin Al Olama, Ali ; Dadaev, Tokhir ; Hazelett, Dennis J ; Li, Qiuyan ; Leongamornlert, Daniel ; Saunders, Edward J ; Stephens, Sarah ; Cieza-Borrella, Clara ; Whitmore, Ian ; Benlloch Garcia, Sara ; Giles, Graham G ; Southey, Melissa C ; Fitzgerald, Liesel ; Gronberg, Henrik ; Wiklund, Fredrik ; Aly, Markus ; Henderson, Brian E ; Schumacher, Fredrick ; Haiman, Christopher A ; Schleutker, Johanna ; Wahlfors, Tiina ; Tammela, Teuvo L ; Nordestgaard, Børge G ; Key, Tim J ; Travis, Ruth C ; Neal, David E ; Donovan, Jenny L ; Hamdy, Freddie C ; Pharoah, Paul ; Pashayan, Nora ; Khaw, Kay-Tee ; Stanford, Janet L ; Thibodeau, Stephen N ; Mcdonnell, Shannon K ; Schaid, Daniel J ; Maier, Christiane ; Vogel, Walther ; Luedeke, Manuel ; Herkommer, Kathleen ; Kibel, Adam S ; Cybulski, Cezary ; Wokołorczyk, Dominika ; Kluzniak, Wojciech ; Cannon-Albright, Lisa ; Brenner, Hermann ; Butterbach, Katja ; Arndt, Volker ; Park, Jong Y ; The PRACTICAL Consortium(Peter Iversen, Martin Andreas Røder, members) ; Iversen, Peter (Redaktør) ; Røder, Martin Andreas (Redaktør). / Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans. I: Human Molecular Genetics. 2015 ; Bind 24, Nr. 19. s. 5589-602.

Bibtex

@article{82b1eb8f7f7b4dbbb600baf79d6cb372,
title = "Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans",
abstract = "Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9{\%} of the familial relative risk of PrCa, an 8.9{\%} improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.",
author = "{Amin Al Olama}, Ali and Tokhir Dadaev and Hazelett, {Dennis J} and Qiuyan Li and Daniel Leongamornlert and Saunders, {Edward J} and Sarah Stephens and Clara Cieza-Borrella and Ian Whitmore and {Benlloch Garcia}, Sara and Giles, {Graham G} and Southey, {Melissa C} and Liesel Fitzgerald and Henrik Gronberg and Fredrik Wiklund and Markus Aly and Henderson, {Brian E} and Fredrick Schumacher and Haiman, {Christopher A} and Johanna Schleutker and Tiina Wahlfors and Tammela, {Teuvo L} and Nordestgaard, {B{\o}rge G} and Key, {Tim J} and Travis, {Ruth C} and Neal, {David E} and Donovan, {Jenny L} and Hamdy, {Freddie C} and Paul Pharoah and Nora Pashayan and Kay-Tee Khaw and Stanford, {Janet L} and Thibodeau, {Stephen N} and Mcdonnell, {Shannon K} and Schaid, {Daniel J} and Christiane Maier and Walther Vogel and Manuel Luedeke and Kathleen Herkommer and Kibel, {Adam S} and Cezary Cybulski and Dominika Wokołorczyk and Wojciech Kluzniak and Lisa Cannon-Albright and Hermann Brenner and Katja Butterbach and Volker Arndt and Park, {Jong Y} and {The PRACTICAL Consortium(Peter Iversen, Martin Andreas R{\o}der, members)} and Peter Iversen and R{\o}der, {Martin Andreas}",
note = "{\circledC} The Author 2015. Published by Oxford University Press.",
year = "2015",
month = "10",
day = "1",
doi = "10.1093/hmg/ddv203",
language = "English",
volume = "24",
pages = "5589--602",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "19",

}

RIS

TY - JOUR

T1 - Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

AU - Amin Al Olama, Ali

AU - Dadaev, Tokhir

AU - Hazelett, Dennis J

AU - Li, Qiuyan

AU - Leongamornlert, Daniel

AU - Saunders, Edward J

AU - Stephens, Sarah

AU - Cieza-Borrella, Clara

AU - Whitmore, Ian

AU - Benlloch Garcia, Sara

AU - Giles, Graham G

AU - Southey, Melissa C

AU - Fitzgerald, Liesel

AU - Gronberg, Henrik

AU - Wiklund, Fredrik

AU - Aly, Markus

AU - Henderson, Brian E

AU - Schumacher, Fredrick

AU - Haiman, Christopher A

AU - Schleutker, Johanna

AU - Wahlfors, Tiina

AU - Tammela, Teuvo L

AU - Nordestgaard, Børge G

AU - Key, Tim J

AU - Travis, Ruth C

AU - Neal, David E

AU - Donovan, Jenny L

AU - Hamdy, Freddie C

AU - Pharoah, Paul

AU - Pashayan, Nora

AU - Khaw, Kay-Tee

AU - Stanford, Janet L

AU - Thibodeau, Stephen N

AU - Mcdonnell, Shannon K

AU - Schaid, Daniel J

AU - Maier, Christiane

AU - Vogel, Walther

AU - Luedeke, Manuel

AU - Herkommer, Kathleen

AU - Kibel, Adam S

AU - Cybulski, Cezary

AU - Wokołorczyk, Dominika

AU - Kluzniak, Wojciech

AU - Cannon-Albright, Lisa

AU - Brenner, Hermann

AU - Butterbach, Katja

AU - Arndt, Volker

AU - Park, Jong Y

AU - The PRACTICAL Consortium(Peter Iversen, Martin Andreas Røder, members)

A2 - Iversen, Peter

A2 - Røder, Martin Andreas

N1 - © The Author 2015. Published by Oxford University Press.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

AB - Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region.

U2 - 10.1093/hmg/ddv203

DO - 10.1093/hmg/ddv203

M3 - Journal article

VL - 24

SP - 5589

EP - 5602

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 19

ER -

ID: 45698886