Journal Article

DKFZ-2020-01361

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The effect of sample size on polygenic hazard models for prostate cancer.

Karunamuni, R. A. ; Huynh-Le, M.-P. ; Fan, C. C. ; Eeles, R. A. ; Easton, D. F. ; Kote-Jarai, Z. ; Amin Al Olama, A. ; Benlloch Garcia, S. ; Muir, K. ; Gronberg, H. ; Wiklund, F. ; Aly, M. ; Schleutker, J. ; Sipeky, C. ; Tammela, T. L. J. ; Nordestgaard, B. G. ; Key, T. J. ; Travis, R. C. ; Neal, D. E. ; Donovan, J. L. ; Hamdy, F. C. ; Pharoah, P. ; Pashayan, N. ; Khaw, K.-T. ; Thibodeau, S. N. ; McDonnell, S. K. ; Schaid, D. J. ; Maier, C. ; Vogel, W. ; Luedeke, M. ; Herkommer, K. ; Kibel, A. S. ; Cybulski, C. ; Wokolorczyk, D. ; Kluzniak, W. ; Cannon-Albright, L. ; Brenner, H.DKFZ* ; Schöttker, B.DKFZ* ; Holleczek, B.DKFZ* ; Park, J. Y. ; Sellers, T. A. ; Lin, H.-Y. ; Slavov, C. ; Kaneva, R. ; Mitev, V. ; Batra, J. ; Clements, J. A. ; Spurdle, A. ; BioResource, A. P. C. (Collaboration Author) ; Teixeira, M. R. ; Paulo, P. ; Maia, S. ; Pandha, H. ; Michael, A. ; Mills, I. G. ; Andreassen, O. A. ; Dale, A. M. ; Seibert, T. M. ; Consortium, P. (Collaboration Author)

2020
Stockton Press Basingstoke

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Please use a persistent id in citations: doi:10.1038/s41431-020-0664-2

Abstract: We determined the effect of sample size on performance of polygenic hazard score (PHS) models in prostate cancer. Age and genotypes were obtained for 40,861 men from the PRACTICAL consortium. The dataset included 201,590 SNPs per subject, and was split into training and testing sets. Established-SNP models considered 65 SNPs that had been previously associated with prostate cancer. Discovery-SNP models used stepwise selection to identify new SNPs. The performance of each PHS model was calculated for random sizes of the training set. The performance of a representative Established-SNP model was estimated for random sizes of the testing set. Mean HR98/50 (hazard ratio of top 2% to average in test set) of the Established-SNP model increased from 1.73 [95% CI: 1.69-1.77] to 2.41 [2.40-2.43] when the number of training samples was increased from 1 thousand to 30 thousand. Corresponding HR98/50 of the Discovery-SNP model increased from 1.05 [0.93-1.18] to 2.19 [2.16-2.23]. HR98/50 of a representative Established-SNP model using testing set sample sizes of 0.6 thousand and 6 thousand observations were 1.78 [1.70-1.85] and 1.73 [1.71-1.76], respectively. We estimate that a study population of 20 thousand men is required to develop Discovery-SNP PHS models while 10 thousand men should be sufficient for Established-SNP models.

Note: 2020 Oct;28(10):1467-1475

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

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