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Prediction of individual genetic risk to prostate cancer using a polygenic score
The Prostate, 2015-09, Vol.75 (13), p.1467-1474
Szulkin, Robert
Whitington, Thomas
Eklund, Martin
Aly, Markus
Eeles, Rosalind A.
Easton, Douglas
Kote-Jarai, ZSofia
Amin Al Olama, Ali
Benlloch, Sara
Muir, Kenneth
Giles, Graham G.
Southey, Melissa C.
Fitzgerald, Liesel M.
Henderson, Brian E.
Schumacher, Fredrick
Haiman, Christopher A.
Schleutker, Johanna
Wahlfors, Tiina
Tammela, Teuvo LJ
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
Lubiński, Jan
Kluźniak, Wojciech
Cannon-Albright, Lisa
Brenner, Hermann
Butterbach, Katja
Stegmaier, Christa
Park, Jong Y.
Sellers, Thomas
Lim, Hui-Yi
Slavov, Chavdar
Kaneva, Radka
Mitev, Vanio
Batra, Jyotsna
Clements, Judith A.
BioResource, The Australian Prostate Cancer
Spurdle, Amanda
Teixeira, Manuel R.
Paulo, Paula
Maia, Sofia
Pandha, Hardev
Michael, Agnieszka
Kierzek, Andrzej
consortium, the PRACTICAL
Gronberg, Henrik
Wiklund, Fredrik
2015
Details
Autor(en) / Beteiligte
Szulkin, Robert
Whitington, Thomas
Eklund, Martin
Aly, Markus
Eeles, Rosalind A.
Easton, Douglas
Kote-Jarai, ZSofia
Amin Al Olama, Ali
Benlloch, Sara
Muir, Kenneth
Giles, Graham G.
Southey, Melissa C.
Fitzgerald, Liesel M.
Henderson, Brian E.
Schumacher, Fredrick
Haiman, Christopher A.
Schleutker, Johanna
Wahlfors, Tiina
Tammela, Teuvo LJ
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
Lubiński, Jan
Kluźniak, Wojciech
Cannon-Albright, Lisa
Brenner, Hermann
Butterbach, Katja
Stegmaier, Christa
Park, Jong Y.
Sellers, Thomas
Lim, Hui-Yi
Slavov, Chavdar
Kaneva, Radka
Mitev, Vanio
Batra, Jyotsna
Clements, Judith A.
BioResource, The Australian Prostate Cancer
Spurdle, Amanda
Teixeira, Manuel R.
Paulo, Paula
Maia, Sofia
Pandha, Hardev
Michael, Agnieszka
Kierzek, Andrzej
consortium, the PRACTICAL
Gronberg, Henrik
Wiklund, Fredrik
Titel
Prediction of individual genetic risk to prostate cancer using a polygenic score
Ist Teil von
The Prostate, 2015-09, Vol.75 (13), p.1467-1474
Ort / Verlag
United States: Blackwell Publishing Ltd
Erscheinungsjahr
2015
Link zum Volltext
Quelle
Wiley Online Library
Beschreibungen/Notizen
BACKGROUND Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome‐wide significant level will improve disease prediction. METHODS We built polygenic risk scores in a large training set comprising over 25,000 individuals. Initially 65 established prostate cancer susceptibility variants were selected. After LD pruning additional variants were prioritized based on their association with prostate cancer. Six‐fold cross validation was performed to assess genetic risk scores and optimize the number of additional variants to be included. The final model was evaluated in an independent study population including 1,370 cases and 1,239 controls. RESULTS The polygenic risk score with 65 established susceptibility variants provided an area under the curve (AUC) of 0.67. Adding an additional 68 novel variants significantly increased the AUC to 0.68 (P = 0.0012) and the net reclassification index with 0.21 (P = 8.5E‐08). All novel variants were located in genomic regions established as associated with prostate cancer risk. CONCLUSIONS Inclusion of additional genetic variants from established prostate cancer susceptibility regions improves disease prediction. Prostate 75:1467–1474, 2015. © 2015 Wiley Periodicals, Inc.
Sprache
Englisch
Identifikatoren
ISSN: 0270-4137, 1097-0045
eISSN: 1097-0045
DOI: 10.1002/pros.23037
Titel-ID: cdi_swepub_primary_oai_prod_swepub_kib_ki_se_131812275
Format
–
Schlagworte
Genetic Markers
,
Genetic Predisposition to Disease
,
Genetic Variation
,
Humans
,
Linkage Disequilibrium
,
Male
,
Medicin och hälsovetenskap
,
polygenic risk score
,
prostate cancer
,
Prostatic Neoplasms - genetics
,
Risk Factors
,
risk prediction
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