PGS Publication: PGP000333

Publication Information (EuropePMC)
Title Stroke genetics informs drug discovery and risk prediction across ancestries
PubMed ID 36180795(Europe PMC)
doi 10.1038/s41586-022-05165-3
Publication Date Sept. 30, 2022
Journal Nature
Author(s) Mishra A, Malik R, Hachiya T, Jürgenson T, Namba S, Posner DC, Kamanu FK, Koido M, Le Grand Q, Shi M, He Y, Georgakis MK, Caro I, Krebs K, Liaw YC, Vaura FC, Lin K, Winsvold BS, Srinivasasainagendra V, Parodi L, Bae HJ, Chauhan G, Chong MR, Tomppo L, Akinyemi R, Roshchupkin GV, Habib N, Jee YH, Thomassen JQ, Abedi V, Cárcel-Márquez J, Nygaard M, Leonard HL, Yang C, Yonova-Doing E, Knol MJ, Lewis AJ, Judy RL, Ago T, Amouyel P, Armstrong ND, Bakker MK, Bartz TM, Bennett DA, Bis JC, Bordes C, Børte S, Cain A, Ridker PM, Cho K, Chen Z, Cruchaga C, Cole JW, de Jager PL, de Cid R, Endres M, Ferreira LE, Geerlings MI, Gasca NC, Gudnason V, Hata J, He J, Heath AK, Ho YL, Havulinna AS, Hopewell JC, Hyacinth HI, Inouye M, Jacob MA, Jeon CE, Jern C, Kamouchi M, Keene KL, Kitazono T, Kittner SJ, Konuma T, Kumar A, Lacaze P, Launer LJ, Lee KJ, Lepik K, Li J, Li L, Manichaikul A, Markus HS, Marston NA, Meitinger T, Mitchell BD, Montellano FA, Morisaki T, Mosley TH, Nalls MA, Nordestgaard BG, O’Donnell MJ, Okada Y, Onland-Moret NC, Ovbiagele B, Peters A, Psaty BM, Rich SS, Rosand J, Sabatine MS, Sacco RL, Saleheen D, Sandset EC, Salomaa V, Sargurupremraj M, Sasaki M, Satizabal CL, Schmidt CO, Shimizu A, Smith NL, Sloane KL , Sutoh Y, Sun YV, Tanno K, Tiedt S, Tatlisumak T, Torres-Aguila NP, Tiwari HK, Trégouët DA, Trompet S, Tuladhar AM, Tybjærg-Hansen A, van Vugt M, Vibo R, Verma SS, Wiggins KL, Wennberg P, Woo D, Wilson PWF, Xu H, Yang Q, Yoon K, The COMPASS Consortium, The INVENT Consortium, The Dutch Parelsnoer Initiative (PSI) Cerebrovascular Disease Study Group, The Estonian Biobank, The PRECISEQ Consortium, The FinnGen Consortium, The NINDS Stroke Genetics Network (SiGN), The MEGASTROKE Consortium, The SIREN Consortium, The China Kadoorie Biobank Collaborative Group, The VA Million Veteran Program, The International Stroke Genetics Consortium (ISGC), The Biobank Japan, The CHARGE Consortium, The GIGASTROKE Consortium, Millwood IY, Gieger C, Ninomiya T, Grabe HJ, Jukema JW, Rissanen IL, Strbian D, Kim YJ, Chen PH, Mayerhofer E, Howson JMM, Irvin MR, Adams H, Wassertheil-Smoller S, Christensen K, Ikram MA, Rundek T, Worrall BB, Lathrop M, Riaz M, Simonsick EM, Kõrv J, França PHC, Zand R, Prasad K, Frikke-Schmidt R, de Leeuw FE, Liman T, Haeusler KG, Ruigrok YM, Heuschmann PU, Longstreth WT, Jung KJ, Bastarache L, Paré G, Damrauer SM, Chasman DI, Rotter JI, Anderson CD, Zwart JA, Niiranen TJ, Fornage M, Liaw YP, Seshadri S, Fernández-Cadenas I, Walters RG, Ruff CT, Owolabi MO, Huffman JE, Milani L, Kamatani Y, Dichgans M, Debette S.
Released in PGS Catalog: Sept. 29, 2022

Associated Polygenic Score(s)

Filter PGS by Participant Ancestry
Individuals included in:
G - Source of Variant Associations (GWAS)
D - Score Development/Training
E - PGS Evaluation
List of ancestries includes:
Display options:
Ancestry legend
Multi-ancestry (including European)
Multi-ancestry (excluding European)
African
East Asian
South Asian
Additional Asian Ancestries
European
Greater Middle Eastern
Hispanic or Latin American
Additional Diverse Ancestries
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)
PGS002725
(GIGASTROKE_iPGS_EAS)
 PGP000333 |
Mishra A et al. Nature (2022)
 Ischemic stroke stroke,
Ischemic stroke		 6,010,730
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS002725/ScoringFiles/PGS002725.txt.gz
PGS002724
(GIGASTROKE_iPGS_EUR)
 PGP000333 |
Mishra A et al. Nature (2022)
 Ischemic stroke stroke,
Ischemic stroke		 1,213,574
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS002724/ScoringFiles/PGS002724.txt.gz

External PGS Evaluated 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)
PGS000039
(metaGRS_ischaemicstroke)
 PGP000027 |
Abraham G et al. Nat Commun (2019)
 Ischemic stroke stroke,
Ischemic stroke		 3,225,583
https://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000039/ScoringFiles/PGS000039.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
PPM014736 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009879|
European Ancestry|
403,489 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: incident ischemic stroke cases HR: 1.19 [1.16, 1.21] C-index: 0.645 ∆C-index (improvement in C-index over covariates-only model): 0.01 age, sex, 5 PCs —
PPM014747 PGS002725
(GIGASTROKE_iPGS_EAS)
 PSS009881|
East Asian Ancestry|
87,682 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: prevalent ischemic stroke cases OR: 1.18 [1.12, 1.25] AUROC: 0.765 ∆AUROC (improvement in AUROC over covariates-only model): 0.003 age, sex, 5 PCs —
PPM014737 PGS000039
(metaGRS_ischaemicstroke)
 PSS009879|
European Ancestry|
403,489 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: incident ischemic stroke cases HR: 1.13 [1.1, 1.15] C-index: 0.64 ∆C-index (improvement in C-index over covariates-only model): 0.006 age, sex, 5 PCs —
PPM014738 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009876|
European Ancestry|
51,288 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: incident ischemic stroke cases HR: 1.19 [1.11, 1.27] C-index: 0.644 ∆C-index (improvement in C-index over covariates-only model): 0.008 age, sex, 5 PCs —
PPM014739 PGS000039
(metaGRS_ischaemicstroke)
 PSS009876|
European Ancestry|
51,288 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: incident ischemic stroke cases HR: 1.14 [1.06, 1.21] C-index: 0.641 ∆C-index (improvement in C-index over covariates-only model): 0.006 age, sex, 5 PCs —
PPM014740 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009878|
African Ancestry|
107,343 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: incident ischemic stroke cases HR: 1.11 [1.06, 1.17] C-index: 0.653 ∆C-index (improvement in C-index over covariates-only model): 0.003 age, sex, 5 PCs —
PPM014741 PGS000039
(metaGRS_ischaemicstroke)
 PSS009878|
African Ancestry|
107,343 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: incident ischemic stroke cases HR: 1.09 [1.04, 1.14] C-index: 0.652 ∆C-index (improvement in C-index over covariates-only model): 0.002 age, sex, 5 PCs —
PPM014742 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009880|
African Ancestry|
3,434 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: prevalent ischemic stroke cases OR: 1.09 [1.02, 1.17] AUROC: 0.548 ∆AUROC (improvement in AUROC over covariates-only model): 0.007 age, sex, 5 PCs —
PPM014744 PGS002725
(GIGASTROKE_iPGS_EAS)
 PSS009875|
East Asian Ancestry|
41,929 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: prevalent ischemic stroke cases OR: 1.33 [1.26, 1.4] AUROC: 0.653 ∆AUROC (improvement in AUROC over covariates-only model): 0.019 age, sex, 5 PCs —
PPM014745 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009875|
East Asian Ancestry|
41,929 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: prevalent ischemic stroke cases OR: 1.18 [1.12, 1.25] AUROC: 0.643 ∆AUROC (improvement in AUROC over covariates-only model): 0.009 age, sex, 5 PCs —
PPM014748 PGS000039
(metaGRS_ischaemicstroke)
 PSS009881|
East Asian Ancestry|
87,682 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: prevalent ischemic stroke cases OR: 1.1 [1.04, 1.16] AUROC: 0.763 ∆AUROC (improvement in AUROC over covariates-only model): 0.001 age, sex, 5 PCs —
PPM014734 PGS002724
(GIGASTROKE_iPGS_EUR)
 PSS009877|
European Ancestry|
102,099 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
 Reported Trait: incident ischemic stroke cases HR: 1.26 [1.19, 1.34] C-index: 0.631 ∆C-index (improvement in C-index over covariates-only model): 0.027 age, sex, 5 PCs —
PPM014735 PGS000039
(metaGRS_ischaemicstroke)
 PSS009877|
European Ancestry|
102,099 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: incident ischemic stroke cases HR: 1.19 [1.12, 1.26] C-index: 0.618 ∆C-index (improvement in C-index over covariates-only model): 0.014 age, sex, 5 PCs —
PPM014743 PGS000039
(metaGRS_ischaemicstroke)
 PSS009880|
African Ancestry|
3,434 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: prevalent ischemic stroke cases OR: 1.07 [1.0, 1.15] AUROC: 0.547 ∆AUROC (improvement in AUROC over covariates-only model): 0.006 age, sex, 5 PCs —
PPM014746 PGS000039
(metaGRS_ischaemicstroke)
 PSS009875|
East Asian Ancestry|
41,929 individuals
 PGP000333 |
Mishra A et al. Nature (2022)
|Ext.		 Reported Trait: prevalent ischemic stroke cases OR: 1.17 [1.11, 1.23] AUROC: 0.641 ∆AUROC (improvement in AUROC over covariates-only model): 0.007 age, sex, 5 PCs —

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
PSS009879 Ischemic stroke —
[
  • 8,392 cases
  • , 395,097 controls
]
 — European
(European)		 — MVP —
PSS009880 Ischemic stroke —
[
  • 1,691 cases
  • , 1,743 controls
]
 — Sub-Saharan African
(Nigerian)		 — NR Stroke Investigative Research & Educational Network (SIREN)
PSS009881 Ischemic stroke —
[
  • 1,399 cases
  • , 86,283 controls
]
 — East Asian
(Taiwanese)		 — TWB —
PSS009875 Ischemic stroke —
[
  • 1,470 cases
  • , 40,459 controls
]
 — East Asian
(Japanese)		 — BBJ % Male: 70.0% for cases and 53.1% for controls. Age information: Mean (cases) = 69.2 years, sd (cases) = 10.8; Mean (controls) = 66.5 years, sd (controls) = 12.5
PSS009876 Ischemic stroke —
[
  • 960 cases
  • , 50,328 controls
]
 — European — NR ClinicalTrials_EUR
PSS009877 Ischemic stroke Mean = 4.6 years
Sd = 4.8 years
[
  • 1,128 cases
  • , 100,971 controls
]
,
37.8 % Male samples
 Mean = 44.0 years
Sd = 15.7 years		 European
(Estonian)		 — EB —
PSS009878 Ischemic stroke —
[
  • 2,227 cases
  • , 105,116 controls
]
 — African American or Afro-Caribbean
(African American)		 — MVP —