Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

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Dadaev, T (author)

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Article/chapterEnglish2018

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2018-06-11
Springer Science and Business Media LLC,2018

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LIBRIS-ID:oai:prod.swepub.kib.ki.se:138464868
http://kipublications.ki.se/Default.aspx?queryparsed=id:138464868URI
https://doi.org/10.1038/s41467-018-04109-8DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-368171URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

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Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.

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Saunders, EJ (author)
Newcombe, PJ (author)
Anokian, E (author)
Leongamornlert, DA (author)
Brook, MN (author)
Cieza-Borrella, C (author)
Mijuskovic, M (author)
Wakerell, S (author)
Al Olama, AA (author)
Schumacher, FR (author)
Berndt, SI (author)
Benlloch, S (author)
Ahmed, M (author)
Goh, C (author)
Sheng, X (author)
Zhang, Z (author)
Muir, K (author)
Govindasami, K (author)
Lophatananon, A (author)
Stevens, VL (author)
Gapstur, SM (author)
Carter, BD (author)
Tangen, CM (author)
Goodman, P (author)
Thompson, IM (author)
Batra, J (author)
Chambers, S (author)
Moya, L (author)
Clements, J (author)
Horvath, L (author)
Tilley, W (author)
Risbridger, G (author)
Gronberg, HKarolinska Institutet (author)
Aly, MKarolinska Institutet (author)
Nordstrom, TKarolinska Institutet (author)
Pharoah, P (author)
Pashayan, N (author)
Schleutker, J (author)
Tammela, TLJ (author)
Sipeky, C (author)
Auvinen, A (author)
Albanes, D (author)
Weinstein, S (author)
Wolk, AlicjaUppsala universitet,Karolinska Institutet,Ortopedi(Swepub:uu)alwol516 (author)
Hakansson, NKarolinska Institutet (author)
West, C (author)
Dunning, AM (author)
Burnet, N (author)
Mucci, L (author)
Giovannucci, E (author)
Andriole, G (author)
Cussenot, O (author)
Cancel-Tassin, G (author)
Koutros, S (author)
Freeman, LEB (author)
Sorensen, KD (author)
Orntoft, TF (author)
Borre, M (author)
Maehle, L (author)
Grindedal, EM (author)
Neal, DE (author)
Donovan, JL (author)
Hamdy, FC (author)
Martin, RM (author)
Travis, RC (author)
Key, TJ (author)
Hamilton, RJ (author)
Fleshner, NE (author)
Finelli, A (author)
Ingles, SA (author)
Stern, MC (author)
Rosenstein, B (author)
Kerns, S (author)
Ostrer, H (author)
Lu, YJ (author)
Zhang, HW (author)
Feng, N (author)
Mao, X (author)
Guo, X (author)
Wang, GM (author)
Sun, Z (author)
Giles, GG (author)
Southey, MC (author)
MacInnis, RJ (author)
FitzGerald, LM (author)
Kibel, AS (author)
Drake, BF (author)
Vega, A (author)
Gomez-Caamano, A (author)
Fachal, L (author)
Szulkin, RKarolinska Institutet (author)
Eklund, MKarolinska Institutet (author)
Kogevinas, M (author)
Llorca, J (author)
Castano-Vinyals, G (author)
Penney, KL (author)
Stampfer, M (author)
Park, JY (author)
Sellers, TA (author)
Lin, HY (author)
Stanford, JL (author)
Cybulski, C (author)
Wokolorczyk, D (author)
Lubinski, J (author)
Ostrander, EA (author)
Geybels, MS (author)
Nordestgaard, BG (author)
Nielsen, SF (author)
Weisher, M (author)
Bisbjerg, R (author)
Roder, MA (author)
Iversen, P (author)
Brenner, H (author)
Cuk, K (author)
Holleczek, B (author)
Maier, C (author)
Luedeke, M (author)
Schnoeller, T (author)
Kim, J (author)
Logothetis, CJ (author)
John, EM (author)
Teixeira, MR (author)
Paulo, P (author)
Cardoso, M (author)
Neuhausen, SL (author)
Steele, L (author)
Ding, YC (author)
De Ruyck, K (author)
De Meerleer, G (author)
Ost, P (author)
Razack, A (author)
Lim, J (author)
Teo, SH (author)
Lin, DW (author)
Newcomb, LF (author)
Lessel, D (author)
Gamulin, M (author)
Kulis, T (author)
Kaneva, R (author)
Usmani, N (author)
Slavov, C (author)
Mitev, V (author)
Parliament, M (author)
Singhal, S (author)
Claessens, F (author)
Joniau, S (author)
Van den Broeck, T (author)
Larkin, S (author)
Townsend, PA (author)
Aukim-Hastie, C (author)
Gago-Dominguez, M (author)
Castelao, JE (author)
Martinez, ME (author)
Roobol, MJ (author)
Jenster, G (author)
van Schaik, RHN (author)
Menegaux, F (author)
Truong, T (author)
Koudou, YA (author)
Xu, JF (author)
Khaw, KT (author)
Cannon-Albright, L (author)
Pandha, H (author)
Michael, A (author)
Kierzek, A (author)
Thibodeau, SN (author)
McDonnell, SK (author)
Schaid, DJ (author)
Lindstrom, S (author)
Turman, C (author)
Ma, J (author)
Hunter, DJ (author)
Riboli, E (author)
Siddiq, A (author)
Canzian, F (author)
Kolonel, LN (author)
Le Marchand, L (author)
Hoover, RN (author)
Machiela, MJ (author)
Kraft, P (author)
Freedman, M (author)
Wiklund, FKarolinska Institutet (author)
Chanock, S (author)
Henderson, BE (author)
Easton, DF (author)
Haiman, CA (author)
Eeles, RA (author)
Conti, DV (author)
Kote-Jarai, Z (author)
Karolinska InstitutetOrtopedi (creator_code:org_t)

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In:Nature communications: Springer Science and Business Media LLC9:1, s. 2256-2041-1723

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By the author/editor: Dadaev, T; Saunders, EJ; Newcombe, PJ; Anokian, E; Leongamornlert, ...; Brook, MN; show more...; Cieza-Borrella, ...; Mijuskovic, M; Wakerell, S; Al Olama, AA; Schumacher, FR; Berndt, SI; Benlloch, S; Ahmed, M; Goh, C; Sheng, X; Zhang, Z; Muir, K; Govindasami, K; Lophatananon, A; Stevens, VL; Gapstur, SM; Carter, BD; Tangen, CM; Goodman, P; Thompson, IM; Batra, J; Chambers, S; Moya, L; Clements, J; Horvath, L; Tilley, W; Risbridger, G; Gronberg, H; Aly, M; Nordstrom, T; Pharoah, P; Pashayan, N; Schleutker, J; Tammela, TLJ; Sipeky, C; Auvinen, A; Albanes, D; Weinstein, S; Wolk, Alicja; Hakansson, N; West, C; Dunning, AM; Burnet, N; Mucci, L; Giovannucci, E; Andriole, G; Cussenot, O; Cancel-Tassin, G; Koutros, S; Freeman, LEB; Sorensen, KD; Orntoft, TF; Borre, M; Maehle, L; Grindedal, EM; Neal, DE; Donovan, JL; Hamdy, FC; Martin, RM; Travis, RC; Key, TJ; Hamilton, RJ; Fleshner, NE; Finelli, A; Ingles, SA; Stern, MC; Rosenstein, B; Kerns, S; Ostrer, H; Lu, YJ; Zhang, HW; Feng, N; Mao, X; Guo, X; Wang, GM; Sun, Z; Giles, GG; Southey, MC; MacInnis, RJ; FitzGerald, LM; Kibel, AS; Drake, BF; Vega, A; Gomez-Caamano, A; Fachal, L; Szulkin, R; Eklund, M; Kogevinas, M; Llorca, J; Castano-Vinyals, ...; Penney, KL; Stampfer, M; Park, JY; Sellers, TA; Lin, HY; Stanford, JL; Cybulski, C; Wokolorczyk, D; Lubinski, J; Ostrander, EA; Geybels, MS; Nordestgaard, BG; Nielsen, SF; Weisher, M; Bisbjerg, R; Roder, MA; Iversen, P; Brenner, H; Cuk, K; Holleczek, B; Maier, C; Luedeke, M; Schnoeller, T; Kim, J; Logothetis, CJ; John, EM; Teixeira, MR; Paulo, P; Cardoso, M; Neuhausen, SL; Steele, L; Ding, YC; De Ruyck, K; De Meerleer, G; Ost, P; Razack, A; Lim, J; Teo, SH; Lin, DW; Newcomb, LF; Lessel, D; Gamulin, M; Kulis, T; Kaneva, R; Usmani, N; Slavov, C; Mitev, V; Parliament, M; Singhal, S; Claessens, F; Joniau, S; Van den Broeck, ...; Larkin, S; Townsend, PA; Aukim-Hastie, C; Gago-Dominguez, ...; Castelao, JE; Martinez, ME; Roobol, MJ; Jenster, G; van Schaik, RHN; Menegaux, F; Truong, T; Koudou, YA; Xu, JF; Khaw, KT; Cannon-Albright, ...; Pandha, H; Michael, A; Kierzek, A; Thibodeau, SN; McDonnell, SK; Schaid, DJ; Lindstrom, S; Turman, C; Ma, J; Hunter, DJ; Riboli, E; Siddiq, A; Canzian, F; Kolonel, LN; Le Marchand, L; Hoover, RN; Machiela, MJ; Kraft, P; Freedman, M; Wiklund, F; Chanock, S; Henderson, BE; Easton, DF; Haiman, CA; Eeles, RA; Conti, DV; Kote-Jarai, Z; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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