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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Roshan A. Karunamuni
  • Minh Phuong Huynh-Le
  • Chun C. Fan
  • Rosalind A. Eeles
  • Douglas F. Easton
  • ZSofia S. Kote-Jarai
  • Ali Amin Al Olama
  • Sara Benlloch Garcia
  • Kenneth Muir
  • Henrik Gronberg
  • Fredrik Wiklund
  • Markus Aly
  • Johanna Schleutker
  • Csilla Sipeky
  • Teuvo L.J. Tammela
  • Nordestgaard, Børge
  • Tim J. Key
  • Ruth C. Travis
  • David E. Neal
  • Jenny L. Donovan
  • Freddie C. Hamdy
  • Paul Pharoah
  • Nora Pashayan
  • Kay Tee Khaw
  • Stephen N. Thibodeau
  • Shannon K. McDonnell
  • Daniel J. Schaid
  • Christiane Maier
  • Walther Vogel
  • Manuel Luedeke
  • Kathleen Herkommer
  • Adam S. Kibel
  • Cezary Cybulski
  • Dominika Wokolorczyk
  • Wojciech Kluzniak
  • Lisa Cannon-Albright
  • Hermann Brenner
  • Ben Schöttker
  • Bernd Holleczek
  • Jong Y. Park
  • Thomas A. Sellers
  • Hui Yi Lin
  • Chavdar Slavov
  • Radka Kaneva
  • Vanio Mitev
  • Jyotsna Batra
  • Judith A. Clements
  • Amanda Spurdle
  • Manuel R. Teixeira
  • Paula Paulo
  • Australian Prostate Cancer BioResource (APCB)
  • The Practical Consortium

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.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Human Genetics
Vol/bind28
Udgave nummer10
Sider (fra-til)1467-1475
Antal sider9
ISSN1018-4813
DOI
StatusUdgivet - 2020

ID: 261152707