PGS Catalog - Foote IF, Nat Genet (2025) (Publication)

PGS Publication: PGP000735

Publication Information (EuropePMC)
Title	Uncovering the multivariate genetic architecture of frailty with genomic structural equation modeling
PubMed ID	40759756(Europe PMC)
doi	10.1038/s41588-025-02269-0
Publication Date	Aug. 4, 2025
Journal	*Nat Genet*
Author(s)	Foote IF, Flint JP, Fürtjes AE, Lawrence JM, Mullin DS, Fisk JD, Karakach TK, Rutenberg A, Martin NG, Lupton MK, Llewellyn DJ, Ranson JM, Cox SR, Luciano M, Rockwood K, Grotzinger AD.

Released in PGS Catalog: July 24, 2025

Associated Polygenic Score(s)

PGS Developed By This Publication

Polygenic Score ID & Name	PGS Publication ID (PGP)	Reported Trait	Mapped Trait(s) (Ontology)	Number of Variants	Ancestry distribution GWAS Dev Eval	Scoring File (FTP Link)
PGS005223 (F2_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 2 (unhealthy lifestyle) of frailty	frailty measurement	1,719,220	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005223/ScoringFiles/PGS005223.txt.gz
PGS005224 (F3_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 3 (multimorbidity) of frailty	frailty measurement	1,588,232	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005224/ScoringFiles/PGS005224.txt.gz
PGS005225 (F4_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 4 (metabolic/respiratory problems) of frailty	frailty measurement	710,413	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005225/ScoringFiles/PGS005225.txt.gz
PGS005226 (F5_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 5 (poorer cognition) of frailty	frailty measurement	1,715,891	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005226/ScoringFiles/PGS005226.txt.gz
PGS005227 (F6_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 6 (disability) of frailty	frailty measurement	1,726,064	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005227/ScoringFiles/PGS005227.txt.gz
PGS005228 (FI_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Frailty Index	frailty measurement	2,379,429	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005228/ScoringFiles/PGS005228.txt.gz
PGS005229 (FFS_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Fried Frailty Score	frailty measurement	2,761,868	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005229/ScoringFiles/PGS005229.txt.gz
PGS005221 (General_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	General factor of frailty	frailty measurement	943,126	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005221/ScoringFiles/PGS005221.txt.gz
PGS005222 (F1_Frailty)	PGP000735 \| Foote IF et al. Nat Genet (2025)	Factor 1 (social isolation) of frailty	frailty measurement	1,727,299	-	https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005222/ScoringFiles/PGS005222.txt.gz

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)	Evaluated Score	PGS Sample Set ID (PSS)	Performance Source	Trait	PGS Effect Sizes (per SD change)	Classification Metrics	Other Metrics	Covariates Included in the Model	PGS Performance: Other Relevant Information
PPM022621	PGS005222 (F1_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.0 β: 0.0021	—	R²: 0.0 FDR corrected P-value: 0.84	age, sex, PC1-PC10	—
PPM022622	PGS005223 (F2_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.05 β: 0.053	—	R²: 0.0 FDR corrected P-value: 7.50e-07	age, sex, PC1-PC10	—
PPM022623	PGS005224 (F3_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.06 β: 0.056	—	R²: 0.0034 FDR corrected P-value: 1.35e-07	age, sex, PC1-PC10	—
PPM022624	PGS005225 (F4_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.04 β: 0.037	—	R²: 0.0015 FDR corrected P-value: 0.00043	age, sex, PC1-PC10	—
PPM022625	PGS005226 (F5_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.06 β: 0.06	—	R²: 0.004 FDR corrected P-value: 1.22e-08	age, sex, PC1-PC10	—
PPM022626	PGS005227 (F6_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.05 β: 0.046	—	R²: 0.0022 FDR corrected P-value: 2e-05	age, sex, PC1-PC10	—
PPM022627	PGS005221 (General_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.09 β: 0.09	—	R²: 0.009 FDR corrected P-value: 3.29e-08	age, sex, PC1-PC10	—
PPM022628	PGS005228 (FI_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.12 β: 0.11	—	R²: 0.02 FDR corrected P-value: 2.00e-16	age, sex, PC1-PC10	—
PPM022629	PGS005229 (FFS_Frailty)	PSS012044\| European Ancestry\| 7,181 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.08 β: 0.076	—	R²: 0.0138 FDR corrected P-value: 2.48e-06	age, sex, PC1-PC10	—
PPM022630	PGS005222 (F1_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 0.99 β: -0.008	—	R²: 0.0058 FDR corrected P-value: 0.48	age, sex, PC1-PC10	—
PPM022631	PGS005223 (F2_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.03 β: 0.029	—	R²: 0.00015 FDR corrected P-value: 0.02	age, sex, PC1-PC10	—
PPM022632	PGS005224 (F3_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.03 β: 0.03	—	R²: 0.00155 FDR corrected P-value: 0.007	age, sex, PC1-PC10	—
PPM022633	PGS005225 (F4_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.04 β: 0.042	—	R²: 0.0021 FDR corrected P-value: 0.001	age, sex, PC1-PC10	—
PPM022634	PGS005226 (F5_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.01 β: 0.006	—	R²: 0.003 FDR corrected P-value: 0.62	age, sex, PC1-PC10	—
PPM022635	PGS005227 (F6_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.05 β: 0.05	—	R²: 7e-05 FDR corrected P-value: 3.91e-06	age, sex, PC1-PC10	—
PPM022636	PGS005221 (General_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.11 β: 0.1	—	R²: 0.006 FDR corrected P-value: 2.00e-16	age, sex, PC1-PC10	—
PPM022637	PGS005228 (FI_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.11 β: 0.1	—	R²: 0.021 FDR corrected P-value: 9.79e-07	age, sex, PC1-PC10	—
PPM022638	PGS005229 (FFS_Frailty)	PSS012046\| European Ancestry\| 3,265 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.08 β: 0.073	—	R²: 0.03 FDR corrected P-value: 2e-05	age, sex, PC1-PC10	—
PPM022639	PGS005222 (F1_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 0.96 β: -0.037	—	R²: 0.007 FDR corrected P-value: 0.24	age, sex, PC1-PC4	—
PPM022640	PGS005223 (F2_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.06 β: 0.06	—	R²: 0.0 FDR corrected P-value: 0.0502	age, sex, PC1-PC4	—
PPM022641	PGS005224 (F3_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.13 β: 0.12	—	R²: 0.001 FDR corrected P-value: 0.00021	age, sex, PC1-PC4	—
PPM022642	PGS005225 (F4_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.03 β: 0.03	—	R²: 0.011 FDR corrected P-value: 0.331	age, sex, PC1-PC4	—
PPM022643	PGS005226 (F5_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.09 β: 0.082	—	R²: 0.0 FDR corrected P-value: 0.082	age, sex, PC1-PC4	—
PPM022644	PGS005227 (F6_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.05 β: 0.048	—	R²: 0.005 FDR corrected P-value: 0.129	age, sex, PC1-PC4	—
PPM022645	PGS005221 (General_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.08 β: 0.08	—	R²: 0.0002 FDR corrected P-value: 0.00846	age, sex, PC1-PC4	—
PPM022646	PGS005228 (FI_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.15 β: 0.14	—	R²: 0.005 FDR corrected P-value: 3.93e-06	age, sex, PC1-PC4	—
PPM022647	PGS005229 (FFS_Frailty)	PSS012045\| European Ancestry\| 1,005 individuals	PGP000735 \| Foote IF et al. Nat Genet (2025)	Reported Trait: Frailty Index	OR: 1.16 β: 0.15	—	R²: 0.019 FDR corrected P-value: 2.48e-06	age, sex, PC1-PC4	—

Evaluated Samples

PGS Sample Set ID (PSS)	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
PSS012046	—	—	3,265 individuals, 32.0 % Male samples	Mean = 60.34 years Sd = 6.98 years	European	—	PISA	—
PSS012044	—	—	7,181 individuals, 46.0 % Male samples	Mean = 68.45 years	European	—	ELSA	—
PSS012045	—	—	1,005 individuals, 51.0 % Male samples	Mean = 69.6 years Sd = 6.98 years	European	—	LBC	—