PGS Publication: PGP000002

Publication Information (EuropePMC)
Title Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes.
PubMed ID 30554720(Europe PMC)
doi 10.1016/j.ajhg.2018.11.002
Publication Date Dec. 13, 2018
Journal Am J Hum Genet
Author(s) Mavaddat N, Michailidou K, Dennis J, Lush M, Fachal L, Lee A, Tyrer JP, Chen TH, Wang Q, Bolla MK, Yang X, Adank MA, Ahearn T, Aittomäki K, Allen J, Andrulis IL, Anton-Culver H, Antonenkova NN, Arndt V, Aronson KJ, Auer PL, Auvinen P, Barrdahl M, Beane Freeman LE, Beckmann MW, Behrens S, Benitez J, Bermisheva M, Bernstein L, Blomqvist C, Bogdanova NV, Bojesen SE, Bonanni B, Børresen-Dale AL, Brauch H, Bremer M, Brenner H, Brentnall A, Brock IW, Brooks-Wilson A, Brucker SY, Brüning T, Burwinkel B, Campa D, Carter BD, Castelao JE, Chanock SJ, Chlebowski R, Christiansen H, Clarke CL, Collée JM, Cordina-Duverger E, Cornelissen S, Couch FJ, Cox A, Cross SS, Czene K, Daly MB, Devilee P, Dörk T, Dos-Santos-Silva I, Dumont M, Durcan L, Dwek M, Eccles DM, Ekici AB, Eliassen AH, Ellberg C, Engel C, Eriksson M, Evans DG, Fasching PA, Figueroa J, Fletcher O, Flyger H, Försti A, Fritschi L, Gabrielson M, Gago-Dominguez M, Gapstur SM, García-Sáenz JA, Gaudet MM, Georgoulias V, Giles GG, Gilyazova IR, Glendon G, Goldberg MS, Goldgar DE, González-Neira A, Grenaker Alnæs GI, Grip M, Gronwald J, Grundy A, Guénel P, Haeberle L, Hahnen E, Haiman CA, Håkansson N, Hamann U, Hankinson SE, Harkness EF, Hart SN, He W, Hein A, Heyworth J, Hillemanns P, Hollestelle A, Hooning MJ, Hoover RN, Hopper JL, Howell A, Huang G, Humphreys K, Hunter DJ, Jakimovska M, Jakubowska A, Janni W, John EM, Johnson N, Jones ME, Jukkola-Vuorinen A, Jung A, Kaaks R, Kaczmarek K, Kataja V, Keeman R, Kerin MJ, Khusnutdinova E, Kiiski JI, Knight JA, Ko YD, Kosma VM, Koutros S, Kristensen VN, Krüger U, Kühl T, Lambrechts D, Le Marchand L, Lee E, Lejbkowicz F, Lilyquist J, Lindblom A, Lindström S, Lissowska J, Lo WY, Loibl S, Long J, Lubiński J, Lux MP, MacInnis RJ, Maishman T, Makalic E, Maleva Kostovska I, Mannermaa A, Manoukian S, Margolin S, Martens JWM, Martinez ME, Mavroudis D, McLean C, Meindl A, Menon U, Middha P, Miller N, Moreno F, Mulligan AM, Mulot C, Muñoz-Garzon VM, Neuhausen SL, Nevanlinna H, Neven P, Newman WG, Nielsen SF, Nordestgaard BG, Norman A, Offit K, Olson JE, Olsson H, Orr N, Pankratz VS, Park-Simon TW, Perez JIA, Pérez-Barrios C, Peterlongo P, Peto J, Pinchev M, Plaseska-Karanfilska D, Polley EC, Prentice R, Presneau N, Prokofyeva D, Purrington K, Pylkäs K, Rack B, Radice P, Rau-Murthy R, Rennert G, Rennert HS, Rhenius V, Robson M, Romero A, Ruddy KJ, Ruebner M, Saloustros E, Sandler DP, Sawyer EJ, Schmidt DF, Schmutzler RK, Schneeweiss A, Schoemaker MJ, Schumacher F, Schürmann P, Schwentner L, Scott C, Scott RJ, Seynaeve C, Shah M, Sherman ME, Shrubsole MJ, Shu XO, Slager S, Smeets A, Sohn C, Soucy P, Southey MC, Spinelli JJ, Stegmaier C, Stone J, Swerdlow AJ, Tamimi RM, Tapper WJ, Taylor JA, Terry MB, Thöne K, Tollenaar RAEM, Tomlinson I, Truong T, Tzardi M, Ulmer HU, Untch M, Vachon CM, van Veen EM, Vijai J, Weinberg CR, Wendt C, Whittemore AS, Wildiers H, Willett W, Winqvist R, Wolk A, Yang XR, Yannoukakos D, Zhang Y, Zheng W, Ziogas A, ABCTB Investigators, kConFab/AOCS Investigators, NBCS Collaborators, Dunning AM, Thompson DJ, Chenevix-Trench G, Chang-Claude J, Schmidt MK, Hall P, Milne RL, Pharoah PDP, Antoniou AC, Chatterjee N, Kraft P, García-Closas M, Simard J, Easton DF.
Released in PGS: Oct. 14, 2019

Associated Polygenic Score(s)

PGS Developed 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)
PGS000004 PRS313_BC PGP000002 Mavaddat N et al. Am J Hum Genet (2018) Breast Cancer breast carcinoma 313 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000004/ScoringFiles/PGS000004.txt.gz
PGS000005 PRS313_ERpos PGP000002 Mavaddat N et al. Am J Hum Genet (2018) ER-positive Breast Cancer estrogen-receptor positive breast cancer 313 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000005/ScoringFiles/PGS000005.txt.gz
PGS000006 PRS313_ERneg PGP000002 Mavaddat N et al. Am J Hum Genet (2018) ER-negative Breast Cancer estrogen-receptor negative breast cancer 313 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000006/ScoringFiles/PGS000006.txt.gz
PGS000007 PRS3820_BC PGP000002 Mavaddat N et al. Am J Hum Genet (2018) Breast Cancer breast carcinoma 3,820 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000007/ScoringFiles/PGS000007.txt.gz
PGS000008 PRS3820_ERpos PGP000002 Mavaddat N et al. Am J Hum Genet (2018) ER-positive Breast Cancer estrogen-receptor positive breast cancer 3,820 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000008/ScoringFiles/PGS000008.txt.gz
PGS000009 PRS3820_ERneg PGP000002 Mavaddat N et al. Am J Hum Genet (2018) ER-negative Breast Cancer estrogen-receptor negative breast cancer 3,820 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000009/ScoringFiles/PGS000009.txt.gz

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)
PGS000001 PRS77_BC PGP000001 Mavaddat N et al. J Natl Cancer Inst (2015) Breast Cancer breast carcinoma 77 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000001/ScoringFiles/PGS000001.txt.gz
PGS000002 PRS77_ERpos PGP000001 Mavaddat N et al. J Natl Cancer Inst (2015) ER-positive Breast Cancer estrogen-receptor positive breast cancer 77 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000002/ScoringFiles/PGS000002.txt.gz
PGS000003 PRS77_ERneg PGP000001 Mavaddat N et al. J Natl Cancer Inst (2015) ER-negative Breast Cancer estrogen-receptor negative breast cancer 77 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000003/ScoringFiles/PGS000003.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
PPM000005 PGS000004 (PRS313_BC) PSS000007 PGP000002
Mavaddat N et al. (2018)
Reported Trait: Incident breast cancer cases HR: 1.59[1.54, 1.64] study, genetic PCs 1-15 Included only 306 of the 313 SNPs
PPM000004 PGS000004 (PRS313_BC) PSS000004 PGP000002
Mavaddat N et al. (2018)
Reported Trait: Invasive breast cancer OR: 1.61[1.57, 1.65] AUROC: 0.63 study, genetic PCs 1-15
PPM000006 PGS000005 (PRS313_ERpos) PSS000005 PGP000002
Mavaddat N et al. (2018)
Reported Trait: ER-positive breast cancer OR: 1.68[1.63, 1.73] AUROC: 0.641 study, genetic PCs 1-15
PPM000007 PGS000006 (PRS313_ERneg) PSS000006 PGP000002
Mavaddat N et al. (2018)
Reported Trait: ER-negative breast cancer OR: 1.45[1.37, 1.53] AUROC: 0.601 study, genetic PCs 1-15
PPM000008 PGS000007 (PRS3820_BC) PSS000004 PGP000002
Mavaddat N et al. (2018)
Reported Trait: Invasive breast cancer OR: 1.66[1.61, 1.7] AUROC: 0.636 study, genetic PCs 1-15
PPM000009 PGS000008 (PRS3820_ERpos) PSS000005 PGP000002
Mavaddat N et al. (2018)
Reported Trait: ER-positive breast cancer OR: 1.73[1.68, 1.78] AUROC: 0.647 study, genetic PCs 1-15
PPM000010 PGS000009 (PRS3820_ERneg) PSS000006 PGP000002
Mavaddat N et al. (2018)
Reported Trait: ER-negative breast cancer OR: 1.44[1.36, 1.53] AUROC: 0.6 study, genetic PCs 1-15
PPM000011 PGS000001 (PRS77_BC) PSS000004 PGP000002
Mavaddat N et al. (2018)
Ext.
Reported Trait: Invasive breast cancer OR: 1.46[1.42, 1.49] AUROC: 0.603 study, genetic PCs 1-15
PPM000012 PGS000002 (PRS77_ERpos) PSS000005 PGP000002
Mavaddat N et al. (2018)
Ext.
Reported Trait: ER-positive breast cancer OR: 1.52[1.48, 1.56] AUROC: 0.615 study, genetic PCs 1-15
PPM000013 PGS000003 (PRS77_ERneg) PSS000006 PGP000002
Mavaddat N et al. (2018)
Ext.
Reported Trait: ER-negative breast cancer OR: 1.35[1.27, 1.43] AUROC: 0.584 study, genetic PCs 1-15

Evaluated Samples

PGS Sample Set ID
(PSS ID)
Phenotype Definitions and Methods Participant Follow-up Time Sample Numbers Age of Study Participants Sample Ancestry Additional Ancestry Description Cohort(s) Additional Sample/Cohort Information
PSS000004 Invasive breast cancer-affected
[
  • 11,428 cases
  • , 18,323 controls
]
,
0.0 % Male samples
European 10 cohorts
  • AHS
  • ,BGS
  • ,EPIC
  • ,FHRISK
  • ,KARMA
  • ,NHS
  • ,NHS2
  • ,PLCO
  • ,PROCAS
  • ,SISTER
Prospective Test Set
PSS000005 ER-positive breast cancer cases
[
  • 7,992 cases
  • , 3,436 controls
]
,
0.0 % Male samples
European 10 cohorts
  • AHS
  • ,BGS
  • ,EPIC
  • ,FHRISK
  • ,KARMA
  • ,NHS
  • ,NHS2
  • ,PLCO
  • ,PROCAS
  • ,SISTER
Prospective Test Set
PSS000006 ER-negative breast cancer cases
[
  • 1,259 cases
  • , 10,169 controls
]
,
0.0 % Male samples
European 10 cohorts
  • AHS
  • ,BGS
  • ,EPIC
  • ,FHRISK
  • ,KARMA
  • ,NHS
  • ,NHS2
  • ,PLCO
  • ,PROCAS
  • ,SISTER
Prospective Test Set
PSS000007 Incident registry-confirmed invasive breast cancers developed
[
  • 3,215 cases
  • , 186,825 controls
]
,
0.0 % Male samples
European UKB Prospective Test Set (UKB)