Polygenic Score (PGS) ID: PGS000814

Predicted Trait
Reported Trait Low-density lipoprotein cholesterol
Mapped Trait(s) low density lipoprotein cholesterol measurement (EFO_0004611)
Released in PGS Catalog: July 2, 2021
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Score Details

Score Construction
PGS Name GRS12_LDLc
Development Method
Name Lead genome-wide significant SNPs from each locus, 6 APOE diplotypes
Parameters P < 5e-8, SNPs where the lead trait is Low density lipoprotein cholesterol.
Variants
Original Genome Build NR
Number of Variants 12
Effect Weight Type beta
PGS Source
PGS Catalog Publication (PGP) ID PGP000200
Citation (link to publication) Talmud PJ et al. Lancet (2013)
Ancestry Distribution
Source of Variant
Associations (GWAS)
European: 100%
95,454 individuals (100%)
PGS Evaluation
European: 75%
Not Reported: 25%
4 Sample Sets

Development Samples

Source of Variant Associations (GWAS)
Study Identifiers Sample Numbers Sample Ancestry Cohort(s)
GWAS Catalog: GCST000759
Europe PMC: 20686565
95,454 individuals European 23 cohorts
  • AGES
  • ,ARIC
  • ,B58C
  • ,BLSA
  • ,BRIGHT
  • ,CHS
  • ,CoLaus
  • ,DGI
  • ,EPIC-Norfolk
  • ,FHS
  • ,FINRISK
  • ,FUSION
  • ,Fenland
  • ,GENMETS
  • ,GenomEUtwin
  • ,InCHIANTI
  • ,KORA
  • ,LOLIPOP
  • ,MedSTAR
  • ,NFBC
  • ,PennCATH
  • ,RS
  • ,SUVIMAX

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)
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
PPM002503 PSS001124|
European Ancestry|
4,787 individuals
PGP000221 |
Leal LG et al. Mol Genet Genomic Med (2020)
|Ext.
Reported Trait: Low-density lipoprotein cholesterol AUROC: 0.65
PPM002169 PSS001058|
European Ancestry|
3,020 individuals
PGP000200 |
Talmud PJ et al. Lancet (2013)
Reported Trait: Low-density lipoprotein (LDL) cholesterol β: 0.34 [0.31, 0.38] Sex, age, lipid-lowering drug use, body-mass index, diabetes status, smoking status, blood pressure
PPM002168 PSS001058|
European Ancestry|
3,020 individuals
PGP000200 |
Talmud PJ et al. Lancet (2013)
Reported Trait: Low-density lipoprotein (LDL) cholesterol β: 0.33 [0.3, 0.37] : 0.11
PPM002171 PSS001059|
European Ancestry|
3,660 individuals
PGP000200 |
Talmud PJ et al. Lancet (2013)
Reported Trait: Low-density lipoprotein cholesterol level >4.9mmol/L in individuals who have familial hypercholestrolaemia and no known mutation AUROC: 0.65 [0.62, 0.68]
PPM002170 PSS001058|
European Ancestry|
3,020 individuals
PGP000200 |
Talmud PJ et al. Lancet (2013)
Reported Trait: Low-density lipoprotein cholesterol level >4.9mmol/L Risk Ratio (RR, top 10% vs bottom 10%): 4.17 [3.01, 5.78]
PPM002201 PSS001072|
Ancestry Not Reported|
967 individuals
PGP000205 |
Rimbert A et al. Arterioscler Thromb Vasc Biol (2020)
|Ext.
Reported Trait: Hypobetalipoproteinemia Percentage of cases with polygenic etiology (%): 34.0 Polygenic etiology = PRS<10th percentile
PPM002202 PSS001072|
Ancestry Not Reported|
967 individuals
PGP000205 |
Rimbert A et al. Arterioscler Thromb Vasc Biol (2020)
|Ext.
Reported Trait: Liver steatosis Odds Ratio (OR, polygenic vs monogenic hypobetalipoproteinemia cases): 0.13 [0.1, 1.16] Age, sex

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
PSS001124 Individuals with severe hypercholesterolemia (HC) had a LDL-C level > 4.9 mmol/L. 124 individuals had severe HC, based on this criteria. Individuals with intermediate HC had a LDL-C level 3.0 ≤ LDL‐C ≤ 4.9 mmol/L. 1927 individuals had intermediate HC, based on this criteria. Individuals classified as having normal LDL-C levels had LDL-C levels < 3.0 mmol/L. 2733 individuals had normal LDL-C levels, based on this criteria. 4,787 individuals,
48.0 % Male samples
Mean = 31.0 years
Sd = 0.2 years
European NFBC
PSS001058 3,020 individuals,
76.0 % Male samples
Mean = 49.0 years
Sd = 6.0 years
European Whitehall
PSS001059 Cases are individuals with familial hypercholesterolaemia (FH). For the Simon Broome British Heart Foundation Study (SBFH), the diagnostic criteria for FH were defined by the Simon Broome Register criteria as an untreated total cholesterol above 7.5mmol/L or an LDL-C above 4.9mmol/L, and a family history of hypercholesterolaemia and/or early coronary heart disease for “possible FH”, and when together with the presence of tendon xanthomas either in the patient or in a first degree relative, as “definite FH”. Of the 640 FH individuals, 321 have FH with no known mutation, whilst 319 have FH with a known mutation.
[
  • 640 cases
  • , 3,020 controls
]
European Whitehall Cases from the Oxford FH study (OXFH) and the Simon Broome British Heart Foundation Study (SBFH)
PSS001072 Cases were individuals with hypobetalipoproteinemia (HBL). Of the 111 individuals with HBL, 38 had polygenic HBL, 40 had monogenic HBL and 33 had HBL from an unknown cause. Polgenic HBL was defined by a polygenic risk score (PRS) < 10th percentile of controls (PRS < 0.5925). For the 40 monogenic HBL individuals, 38 carried heterozygous APOB loss of fucntion variants and 2 carried heterozygous PCSK9 loss of function variants. In a subset of HBL cases, 7 polygenic cases , 26 monogenic cases and 13 uknown cause cases had liver steatosis. Whilst 17, 6 and 9 individuals did not have liver steatosis, respectively. Liver steatosis was diagnosed by abdominal ultrasonography. Alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transpeptidase were determined by IFCC-standardized enzymatic methods using dedicated commercial kits. Individuals with ALT >1 upper limit of normal (>97.5th percentile) were considered to likely have liver injury.
[
  • 111 cases
  • , 856 controls
]
Not reported NR Cases were obtained from the HYPOCHOL and GENLIP studies. Controls were obtained from the PREGO and GAZEL cohorts and the Finstère area, which are part of the FranceGenRef Consortium.