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

European Journal of Human Genetics : EJHG
Roshan A KarunamuniPRACTICAL Consortium

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 Disc...Continue Reading

References

Jul 17, 1999·Lifetime Data Analysis·T M Therneau, H Li
Aug 19, 2008·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Zsofia Kote-JaraiRosalind A Eeles
Oct 21, 2014·Brain and Behavior·Jessica R MardenM Maria Glymour
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May 4, 2016·Nature Reviews. Genetics·Nilanjan ChatterjeeMontserrat García-Closas
May 24, 2018·Nature Reviews. Genetics·Ali TorkamaniEric J Topol

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Citations

Jan 10, 2021·Prostate Cancer and Prostatic Diseases·Roshan A KarunamuniUNKNOWN PRACTICAL Consortium
Feb 25, 2021·Nature Communications·Minh-Phuong Huynh-LeUNKNOWN PRACTICAL Consortium
Mar 17, 2021·Prostate Cancer and Prostatic Diseases·Minh-Phuong Huynh-LeUNKNOWN PRACTICAL Consortium
Jun 16, 2021·Prostate Cancer and Prostatic Diseases·Roshan A KarunamuniTyler M Seibert
Jul 3, 2021·The Urologic Clinics of North America·Lindsey Byrne, Amanda Ewart Toland
Oct 7, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Lasse PihlstrømOle A Andreassen

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Methods Mentioned

BETA
genotyping
chip

Clinical Trials Mentioned

NCT02044172

Software Mentioned

ProtecT
MATLAB

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