PGS Publication: PGP000182

Publication Information (EuropePMC)
Title Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect.
PubMed ID 33495596(Europe PMC)
doi 10.1038/s41588-020-00762-2
Publication Date Jan. 25, 2021
Journal Nat Genet
Author(s) Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, Kelu Bisabu K, Walsh R, Hoorntje ET, Te Rijdt WP, Buchan RJ, van Velzen HG, van Slegtenhorst MA, Vermeulen JM, Offerhaus JA, Bai W, de Marvao A, Lahrouchi N, Beekman L, Karper JC, Veldink JH, Kayvanpour E, Pantazis A, Baksi AJ, Whiffin N, Mazzarotto F, Sloane G, Suzuki H, Schneider-Luftman D, Elliott P, Richard P, Ader F, Villard E, Lichtner P, Meitinger T, Tanck MWT, van Tintelen JP, Thain A, McCarty D, Hegele RA, Roberts JD, Amyot J, Dubé MP, Cadrin-Tourigny J, Giraldeau G, L'Allier PL, Garceau P, Tardif JC, Boekholdt SM, Lumbers RT, Asselbergs FW, Barton PJR, Cook SA, Prasad SK, O'Regan DP, van der Velden J, Verweij KJH, Talajic M, Lettre G, Pinto YM, Meder B, Charron P, de Boer RA, Christiaans I, Michels M, Wilde AAM, Watkins H, Matthews PM, Ware JS, Bezzina CR.
Released in PGS Catalog: May 28, 2021

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:
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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 PGS Scoring File (FTP Link)
PGS000778
(PRSHCM)
PGP000182 |
Tadros R et al. Nat Genet (2021)
Hypertrophic cardiomyopathy hypertrophic cardiomyopathy 20
-
http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000778/ScoringFiles/PGS000778.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 PGS Scoring File (FTP Link)
PGS000016
(GPS_AF)
PGP000006 |
Khera AV et al. Nat Genet (2018)
Atrial fibrillation atrial fibrillation 6,730,541
http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000016/ScoringFiles/PGS000016.txt.gz - Check Terms/Licenses

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
PPM002016 PGS000778
(PRSHCM)
PSS000999|
Ancestry Not Reported|
368 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Clinical events in individuals with a pathogenic or likely pathogenic sarcomeric variant HR: 1.28 [1.06, 1.54]
β: 0.247 (0.095)
Genetic relatedness matrix, sex Clinical events includes time to septal reduction therapy, cardiac transplantation, sustained ventricular arrhythmia, sudden cardiac death, appropriate ICD therapy or atrial fibrillation/flutter.
PPM002017 PGS000778
(PRSHCM)
PSS001000|
Ancestry Not Reported|
368 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Major clinical events in individuals with a pathogenic or likely pathogenic sarcomeric variant HR: 1.29 [1.04, 1.59]
β: 0.255 (0.108)
Genetic relatedness matrix, sex Major clinical events includes time to septal reduction therapy, cardiac transplantation, sustained ventricular arrhythmia, sudden cardiac death or appropriate ICD therapy.
PPM002018 PGS000778
(PRSHCM)
PSS001004|
Ancestry Not Reported|
368 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Septal reduction therapy in individuals with a pathogenic or likely pathogenic sarcomeric variant HR: 1.36 [1.06, 1.74]
β: 0.304 (0.127)
Genetic relatedness matrix, sex Septal reduction therapy includes time time to septal myectomy or alcohol septal ablation.
PPM002019 PGS000016
(GPS_AF)
PSS000998|
Ancestry Not Reported|
368 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
|Ext.
Reported Trait: Atrial fibrillation or atrial flutter in individuals with a pathogenic or likely pathogenic sarcomeric variant HR: 1.5 [1.17, 1.91]
β: 0.402 (0.124)
Genetic relatedness matrix, sex
PPM002020 PGS000778
(PRSHCM)
PSS001003|
Ancestry Not Reported|
194 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Maximal left ventricular wall thickness indexed to body surface area (mm/m^2) in individuals with a pathogenic or likely pathogenic sarcomeric variant β: 0.731 (0.238) Genetic relatedness matrix Each standard deviation increase in the polgyenic risk score is associated with 0.7 mm m^-2 increase in maximal left ventricular wall thickness.
PPM002021 PGS000778
(PRSHCM)
PSS001002|
Ancestry Not Reported|
214 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Clinical events in in individuals with a pathogenic or likely pathogenic sarcomeric variant HR: 1.53 [1.05, 2.22]
β: 0.422 (0.193)
Genetic relatedness matrix, sex Clinical events includes time to septal reduction therapy, cardiac transplantation, sustained ventricular arrhythmia, sudden cardiac death, appropriate ICD therapy or atrial fibrillation/flutter.
PPM002015 PGS000778
(PRSHCM)
PSS001001|
Ancestry Not Reported|
322 individuals
PGP000182 |
Tadros R et al. Nat Genet (2021)
Reported Trait: Maximal left ventricular wall thickness indexed to body surface area (mm/m^2) in individuals with a pathogenic or likely pathogenic sarcomeric variant β: 0.726 (0.188) Genetic relatedness matrix Each standard deviation increase in the polgyenic risk score is associated with 0.7 mm m^-2 increase in maximal left ventricular wall thickness.

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
PSS000998 All individuals were carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). Cases included individuals who had experienced atrial fibrillation, defined as: time to atrial fibrillation or flutter.
[
  • 70 cases
  • , 298 controls
]
Not reported ERSPC
PSS000999 All individuals were carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). Cases included individuals who had experienced a clinical event, defined as: time to septal reduction therapy, cardiac transplantation, sustained ventricular arrhythmia, sudden cardiac death, appropriate ICD therapy or atrial fibrillation/flutter.
[
  • 122 cases
  • , 246 controls
]
Not reported ERSPC
PSS001000 All individuals were carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). Cases included individuals who had experienced a major ventricular arrhythmia, defined as: time to sustained ventricular arrhythmia, appropriate ICD therapy or sudden cardiac death.
[
  • 30 cases
  • , 338 controls
]
Not reported ERSPC
PSS001001 All individuals were carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). The primary outcome of maximal left ventricular wall thickness is defined as maxLVWT indexed to body surface area (BSA) on last available CMR or TTE prior to septal reduction therapy and cardiac transplantation. LVWT from CMR used whenever available unless TTE performed more than 5 years after last CMR. 322 individuals Not reported ERSPC
PSS001002 All individuals were non-proband carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). Cases included individuals who had experienced a clinical event, defined as: time to septal reduction therapy, cardiac transplantation, sustained ventricular arrhythmia, sudden cardiac death, appropriate ICD therapy or atrial fibrillation/flutter.
[
  • 33 cases
  • , 181 controls
]
Not reported ERSPC
PSS001003 All individuals were non-proband carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). The primary outcome of maximal left ventricular wall thickness (maxLVWT) is defined as maxLVWT indexed to body surface area (BSA) on last available CMR or TTE prior to septal reduction therapy and cardiac transplantation. LVWT from CMR used whenever available unless TTE performed more than 5 years after last CMR. 194 individuals Not reported ERSPC
PSS001004 All individuals were carriers of a pathogenic or likely pathogenic variant (MYBPC3 truncating variant, MYBPC3 non-truncating variant, MYH7 variant, MYL2 variant, other genetic variant). Cases included individuals who had experienced septal reduction therapy, defined as: time to septal myectomy or alcohol septal ablation.
[
  • 66 cases
  • , 302 controls
]
Not reported ERSPC