| Publication Information (EuropePMC) | |
| Title | Genomic and transcriptomic analyses of aortic stenosis enhance therapeutic target discovery and disease prediction. |
| PubMed ID | 41419686(Europe PMC) |
| doi | 10.1038/s41588-025-02417-6 |
| Publication Date | Dec. 19, 2025 |
| Journal | Nat Genet |
| Author(s) | Small AM, Yang TY, Itoh S, Thériault S, Dufresne L, Kurosawa R, Komuro I, Matsuda K, Vy HMT, Farber-Eger EH, Shaffer LL, Boulier KM, Corey KM, Ramaker ME, Laporte F, Schott JJ, Le Scouarnec S, Singh SA, Sonawane AR, Smith HA, Rafaels N, Colorado Center for Personalized Medicine, Ghouse J, Raja AA, Ostrowski SR, Sørensen E, Mikkelsen C, Pedersen OB, Erikstrup C, Ullum H, DBDS Genomic Consortium, Sveinbjornsson G, Gudbjartsson DF, Abner E, Estonian Biobank Research Team, Lee J, Ganna A, Nowak-Göttl U, Finer S, Genes & Health Research Team, Schumacher J, Maj C, Al-Kassou B, Nickenig G, Trenkwalder T, Dreβen M, Krane M, Nöthen MM, Moksnes MR, Brumpton BM, Knight S, Knowlton KU, Nadauld L, Debiec R, Musameh MD, Braund PS, Nelson CP, Czuba T, Melander O, Selvaraj MS, Koyama S, Bhukar R, Ruan Y, Ljungberg J, Damrauer SM, Levin MG, Franke A, Berger K, Ruff CT, Melloni GEM, Kamanu FK, Ito K, Do R, Loos RJF, Schunkert H, Wells QS, Shah SH, Le Tourneau T, Messika-Zeitoun D, Gignoux C, Bundgaard H, Larsson SC, Michaëlsson K, Holm H, Helgadottir A, Esko T, van Heel DA, Mathieu P, Samani NJ, Smith JG, Söderberg S, Rader DJ, Marston NA, Sabatine MS, Pasaniuc B, Cho K, Wilson PWF, O'Donnell CJ, Stefansson K, Bossé Y, Aikawa E, Engert JC, Peloso GM, Natarajan P, Thanassoulis G. |
| 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) |
|---|---|---|---|---|---|---|
| PGS005252 (IAVGC_AS_PRS) |
PGP000745 | Small AM et al. Nat Genet (2025) |
Aortic stenosis | aortic stenosis | 1,119,377 | - |
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS005252/ScoringFiles/PGS005252.txt.gz |
|
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 |
|---|---|---|---|---|---|---|---|---|---|
| PPM022733 | PGS005252 (IAVGC_AS_PRS) |
PSS012066| European Ancestry| 446,895 individuals |
PGP000745 | Small AM et al. Nat Genet (2025) |
Reported Trait: Incident aortic stenosis cases | HR: 1.92 | C-index: 0.87 | — | age, sex, genetic ancestry principal components 1-5, type 2 diabetes, hypertension, coronary artery disease, hyperlipidemia, body mass index, current smoking, renal failure. | — |
| PPM022734 | PGS005252 (IAVGC_AS_PRS) |
PSS012065| European Ancestry| 34,024 individuals |
PGP000745 | Small AM et al. Nat Genet (2025) |
Reported Trait: Any aortic stenosis | OR: 1.43 | — | — | age, sex, genetic ancestry principal components 1-5, type 2 diabetes, hypertension, coronary artery disease, hyperlipidemia, body mass index, current smoking, renal failure. | — |
| PPM022735 | PGS005252 (IAVGC_AS_PRS) |
PSS012064| European Ancestry| 59,866 individuals |
PGP000745 | Small AM et al. Nat Genet (2025) |
Reported Trait: Incident aortic stenosis cases | HR: 1.8 | C-index: 0.76 | — | age, sex, genetic ancestry principal components 1-5, type 2 diabetes, hypertension, coronary artery disease, hyperlipidemia, body mass index, current smoking, renal failure. | — |
|
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 |
|---|---|---|---|---|---|---|---|---|
| PSS012064 | The aortic stenosis PRS was tested for its association with aortic stenosis using safety data from the TIMI trials. Aortic stenosis was called for any adverse event referencing aortic stenosis, including new or worsening aortic stenosis. | — | [
|
— | European (European) |
— | ENGAGE_AF-TIMI_48, FOURIER, PEGASUS-TIMI_54, SAVOR-TIMI_53, SOLID-TIMI_52 | These data also include samples from DECLARE-TIMI 58 (not in the cohort refr. List) |
| PSS012065 | IAVGC phenotype definition (see detailed description in manuscript) | — | [
|
— | European (European) |
— | UCLA | — |
| PSS012066 | IAVGC phenotype definition (see detailed description in manuscript) | — | [
|
Mean = 62.1 years | European (European) |
— | UKB | — |