PGS Publication: PGP000733

Publication Information (EuropePMC)
Title Genome-wide association study and polygenic risk prediction of hypothyroidism.
PubMed ID 41238958(Europe PMC)
doi 10.1038/s41588-025-02410-z
Publication Date Nov. 14, 2025
Journal Nat Genet
Author(s) Rand SA, Ahlberg G, Tragante V, Monfort LM, Zheng C, Feldt-Rasmussen U, Klose MC, Teder-Laving M, Metspalu A, Poulsen HE, Ellervik C, Nygaard B, Erikstrup C, Bruun MT, A Jensen B, Ullum H, Brunak S, DBDS Genomic Consortium, Estonian Biobank Research Team, 23andMe Research Team, Schwinn M, Ostrowski SR, Pedersen OB, Sørensen E, Jonsdottir I, Gudbjartsson DF, Thorleifsson G, Holm H, Saevarsdottir S, Stefansson K, Salling Olesen M, Bundgaard H, Ghouse J.
Released in PGS Catalog: Nov. 10, 2025

Associated Polygenic Score(s)

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Individuals included in:
G - Source of Variant Associations (GWAS)
D - Score Development/Training
E - PGS Evaluation
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Not Reported

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)
PGS005218
(prsweights_hypothyroidism_excl23)
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Hypothyroidism hypothyroidism 1,110,091
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005218/ScoringFiles/PGS005218.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
PPM022615 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Incident hypothyroidism — AUROC: 0.698 [0.693, 0.703] — age, sex, PC1, PC2, PC3, PC4 Evaluated in UKB for only incident hypothyroidism
PPM022613 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Hypothyroidism OR: 2.01 [1.99, 2.03] — — age, sex, PC1, PC2, PC3, PC4 Evaluated in UKB for both incident and prevalent hypothyroidism
PPM022614 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Hypothyroidism OR: 2.0 [1.95, 2.17] — — age, sex, PC1, PC2, PC3, PC4 Evaluated in GESUS for both incident and prevalent hypothyroidism
PPM022617 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Incident hypothyroidism — AUROC: 0.859 [0.821, 0.897] — age, sex, TSH, T4, anti-TPO, PC1, PC2, PC3, PC4 Evaluated in GESUS which measured anti-TPO and thyroid hormones at baseline. Prevalent hypothyroidism was excluded
PPM022618 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Incident hypothyroidism among anti-TPO negative individuals (anti-TPO < 100 U/mL) — — Hazard ratio (HR, high vs middle percentile): 1.97 [1.06, 3.68] age, sex, PC1, PC2, PC3, PC4 Evaluated in GESUS which measured anti-TPO and thyroid hormones at baseline. Only individuals with anti-TPO < 100 u/mL were considered for this analysis. Prevalent hypothyroidism was excluded
PPM022616 PGS005218
(prsweights_hypothyroidism_excl23)
 PSS012042|
European Ancestry|
441,692 individuals
 PGP000733 |
Rand SA et al. Nat Genet (2025)
 Reported Trait: Progression from subclinical to overt hypothyroidism — — Hazard ratio (HR, high vs middle percentile): 1.43 [1.37, 1.61] age, sex, PC1, PC2, PC3, PC4 Evaluated in UKB primary care date, only in individuals that developed subclinical hypothyroidism after enrollment to UKB. Prevalent hypothyroidism was excluded

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
PSS012042 ICD10: E038, E039, E063 Self-reported hypothyroidism ATC: H03A or dnd codes for levothyroxine Cases excluded ICD10:DE05[0-9] —
[
  • 32,304 cases
  • , 399,000 controls
]
 — European
(White British)		 — UKB —
PSS012042 ICD10: E038, E039, E063 ATC: H03A Excluded individuals with ICD10: E05[0-9] —
[
  • 760 cases
  • , 9,628 controls
]
 — European
(Danish)		 — GESUS —