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The effect of sample size on polygenic hazard models for prostate cancer.

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ICR Author
Eeles, Rosalind
Kote-Jarai, Zsofia
Author
Karunamuni, RA
Huynh-Le, M-P
Fan, CC
Eeles, RA
Easton, DF
Kote-Jarai, Z
Amin Al Olama, A
Benlloch Garcia, S
Muir, K
Gronberg, H
Wiklund, F
Aly, M
Schleutker, J
Sipeky, C
Tammela, TLJ
Nordestgaard, BG
Key, TJ
Travis, RC
Neal, DE
Donovan, JL
Hamdy, FC
Pharoah, P
Pashayan, N
Khaw, K-T
Thibodeau, SN
McDonnell, SK
Schaid, DJ
Maier, C
Vogel, W
Luedeke, M
Herkommer, K
Kibel, AS
Cybulski, C
Wokolorczyk, D
Kluzniak, W
Cannon-Albright, L
Brenner, H
Schöttker, B
Holleczek, B
Park, JY
Sellers, TA
Lin, H-Y
Slavov, C
Kaneva, R
Mitev, V
Batra, J
Clements, JA
Spurdle, A
Australian Prostate Cancer BioResource (APCB)
Teixeira, MR
Paulo, P
Maia, S
Pandha, H
Michael, A
Mills, IG
Andreassen, OA
Dale, AM
Seibert, TM
PRACTICAL Consortium
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Type
Journal Article
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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 HR 98/50 (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 HR 98/50 of the Discovery-SNP model increased from 1.05 [0.93-1.18] to 2.19 [2.16-2.23]. HR 98/50 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.
URI
https://repository.icr.ac.uk/handle/internal/4770
DOI
https://doi.org/10.1038/s41431-020-0664-2
Collections
  • Genetics and Epidemiology
  • Radiotherapy and Imaging
Subject
Australian Prostate Cancer BioResource (APCB)
PRACTICAL Consortium
Humans
Prostatic Neoplasms
Proportional Hazards Models
Sample Size
Multifactorial Inheritance
Polymorphism, Single Nucleotide
Models, Genetic
Male
Clinical Trials as Topic
Genome-Wide Association Study
Research team
Oncogenetics
Oncogenetics
Language
eng
Date accepted
2020-05-22
Citation
European journal of human genetics : EJHG, 2020, 28 (10), pp. 1467 - 1475

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