PGS Preprint: PGP000058

Publication Information (EuropePMC)
Title Polygenic hazard score predicts aggressive and fatal prostate cancer in multi-ethnic populations
doi 10.1101/19012237
Publication Date Nov. 19, 2019
Journal medRxiv Preprint
Author(s) Huynh-Le M, Fan CC, Karunamuni R, Martinez ME, Eeles RA, Kote-Jarai Z, Muir K, Schleutker J, Pashayan N, Batra J, Grönberg H, Neal DE, Donovan J, Hamdy FC, Martin RM, Nielsen SF, Nordestgaard BG, Wiklund F, Tangen CM, Giles GG, Wolk A, Albanes D, Haiman CA, Travis RC, Blot WJ, Zheng W, Sanderson M, Stanford JL, Mucci LA, West CML, Kibel AS, Cussenot O, Berndt SI, Koutros S, Sørensen KD, Cybulski C, Grindedal EM, Menegaux F, Khaw K, Park JY, Ingles SA, Maier C, Hamilton RJ, Thibodeau SN, Rosenstein BS, Lu Y, Watya S, Vega A, Kogevinas M, Penney KL, Huff C, Teixeira MR, Multigner L, Leach RJ, Cannon-Albright L, Brenner H, John EM, Kaneva R, Logothetis CJ, Neuhausen SL, De Ruyck K, Pandha H, Razack A, Newcomb LF, Fowke J, Gamulin M, Usmani N, Claessens F, Gago-Dominguez M, Townsend PA, Bush WS, Srivastava S, Roobol M, Parent M, Hu JJ, Mills IG, Andreassen OA, Dale AM, Seibert TM, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, The IMPACT Study Steering Committee and Collaborators, Canary P ASS Investigators, The Profile Study Steering Committee, The PRACTICAL Consortium.
Released in PGS: March 27, 2020

Associated Polygenic Score(s)

External PGS Evaluated By This Publication

Polygenic Score (PGS) ID PGS Name PGS Publication (PGP) ID Reported Trait Mapped Trait(s) (Ontology) Number of Variants PGS Scoring File (FTP Link)
PGS000067 PCa_PHS PGP000047
Seibert TM et al. BMJ (2018)
Prostate cancer prostate carcinoma 54 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000067/ScoringFiles/PGS000067.txt.gz

PGS Performance Metrics

Disclaimer: The performance metrics are displayed as reported by the source studies. It is important to note that metrics are not necessarily comparable with each other. For example, metrics depend on the sample characteristics (described by the PGS Catalog Sample Set [PSS] ID), phenotyping, and statistical modelling. Please refer to the source publication for additional guidance on performance.

PGS Performance Metric ID
(PPM ID)
Evaluated Score PGS Sample Set ID
(PSS ID)
Performance Source Trait PGS Effect Sizes
(per SD change)
PGS Classification Metrics Other Metrics Covariates Included in the Model PGS Performance: Other Relevant Information
PPM000394 PGS000067 (PCa_PHS) PSS000224 PGP000058
Huynh-Le M et al. (2019)
Ext. Pre
Reported Trait: Age of prostate cancer death Hazard Ratio (HR; top 20% vs. rest): 5.7[4.6, 7.0] Association between PHS and age-at-onset p-value < 10e-16. Only SNPs directly genotyped on the OncoArray genotyping array were considered. 46 of the score's 54 SNPs were used: 24 directly genotyped, and 22 with acceptable proxies (r2>0.94).
PPM000390 PGS000067 (PCa_PHS) PSS000220 PGP000058
Huynh-Le M et al. (2019)
Ext. Pre
Reported Trait: Age of aggressive prostate cancer onset Hazard Ratio (HR; top 20% vs. rest): 5.9[5.5, 6.3] Association between PHS and age-at-onset p-value < 10e-16. Only SNPs directly genotyped on the OncoArray genotyping array were considered. 46 of the score's 54 SNPs were used: 24 directly genotyped, and 22 with acceptable proxies (r2>0.94).
PPM000391 PGS000067 (PCa_PHS) PSS000223 PGP000058
Huynh-Le M et al. (2019)
Ext. Pre
Reported Trait: Age of aggressive prostate cancer onset Hazard Ratio (HR; top 20% vs. rest): 5.6[5.2, 6.0] Association between PHS and age-at-onset p-value < 10e-16. Only SNPs directly genotyped on the OncoArray genotyping array were considered. 46 of the score's 54 SNPs were used: 24 directly genotyped, and 22 with acceptable proxies (r2>0.94).
PPM000392 PGS000067 (PCa_PHS) PSS000222 PGP000058
Huynh-Le M et al. (2019)
Ext. Pre
Reported Trait: Age of aggressive prostate cancer onset Hazard Ratio (HR; top 20% vs. rest): 5.2[4.8, 5.6] Association between PHS and age-at-onset p-value < 10e-16. Only SNPs directly genotyped on the OncoArray genotyping array were considered. 46 of the score's 54 SNPs were used: 24 directly genotyped, and 22 with acceptable proxies (r2>0.94).
PPM000393 PGS000067 (PCa_PHS) PSS000221 PGP000058
Huynh-Le M et al. (2019)
Ext. Pre
Reported Trait: Age of aggressive prostate cancer onset Hazard Ratio (HR; top 20% vs. rest): 2.4[2.3, 2.6] Association between PHS and age-at-onset p-value < 10e-16. Only SNPs directly genotyped on the OncoArray genotyping array were considered. 46 of the score's 54 SNPs were used: 24 directly genotyped, and 22 with acceptable proxies (r2>0.94).

Evaluated Samples

PGS Sample Set ID
(PSS ID)
Detailed Phenotype Description Participant Follow-up Time Sample Numbers Age of Study Participants Sample Ancestry Additional Ancestry Description Cohort(s) Additional Sample/Cohort Information
PSS000220 Age of onset of aggressive prostate cancer, defined by Gleason score ≥7, PSA ≥10 ng/mL, T3-T4 stage, nodal metastases, or distant metastases
[
  • 26,419 cases
  • , 30,575 controls
]
,
1.0 % Male samples
Other Combined analysis of multiple ancestries, including: European, East Asian, African American, Hawaiian, Hispanic American, South Asian, Black African, Black Caribbean, and Other (not specified) OncoArray_Prostate List of Cohorts available from dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001391.v1.p1
PSS000221 Age of onset of aggressive prostate cancer, defined by Gleason score ≥7, PSA ≥10 ng/mL, T3-T4 stage, nodal metastases, or distant metastases
[
  • 1,424 cases
  • , 3,013 controls
]
,
1.0 % Male samples
African unspecified Subset of OncoArray_APC_onset samples. Determined from genetic PCs via FastPop OncoArray_Prostate List of Cohorts available from dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001391.v1.p1
PSS000222 Age of onset of aggressive prostate cancer, defined by Gleason score ≥7, PSA ≥10 ng/mL, T3-T4 stage, nodal metastases, or distant metastases
[
  • 716 cases
  • , 1,185 controls
]
,
1.0 % Male samples
Asian unspecified Subset of OncoArray_APC_onset samples. Determined from genetic PCs via FastPop OncoArray_Prostate List of Cohorts available from dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001391.v1.p1
PSS000223 Age of onset of aggressive prostate cancer, defined by Gleason score ≥7, PSA ≥10 ng/mL, T3-T4 stage, nodal metastases, or distant metastases
[
  • 24,279 cases
  • , 26,377 controls
]
,
1.0 % Male samples
European Subset of OncoArray_APC_onset samples. Determined from genetic PCs via FastPop OncoArray_Prostate List of Cohorts available from dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001391.v1.p1
PSS000224 Age at death due to prostate cancer.
[
  • 3,983 cases
  • , 30,575 controls
]
,
1.0 % Male samples
Mean = 70.0 years
Iqr = [63.0, 76.0] years
Other Combined analysis of multiple ancestries, including: European, East Asian, African American, Hawaiian, Hispanic American, South Asian, Black African, Black Caribbean, and Other (not specified) OncoArray_Prostate List of Cohorts available from dbGaP: https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001391.v1.p1