Trait: low density lipoprotein cholesterol measurement

Experimental Factor Ontology (EFO) Information
Identifier EFO_0004611
Description
  • The measurement of LDL cholesterol in blood used as a risk indicator for heart disease.
Trait category
Cardiovascular measurement
Lipid or lipoprotein measurement
Synonyms LDL measurement
Mapped term(s) 2 mapped terms
  • SNOMEDCT:113079009
  • NCIt:C105588

Associated Polygenic Score(s)

Polygenic Score (PGS) ID PGS Name PGS Publication (PGP) ID Reported Trait Mapped Trait(s) (Ontology) Number of Variants PGS Scoring File (FTP Link)
PGS000061 GRS_LDL PGP000045 Johnson L et al. PLoS One (2015) low-density lipoprotein (LDL) cholesterol low density lipoprotein cholesterol measurement 37 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000061/ScoringFiles/PGS000061.txt.gz
PGS000065 GLGC2017_LDL PGP000046 Kuchenbaecker K et al. Nat Commun (2019) Low density lipoprotein (HDL) cholesterol low density lipoprotein cholesterol measurement 103 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000065/ScoringFiles/PGS000065.txt.gz
PGS000115 LDL-C_20 PGP000053 Trinder M et al. JAMA Cardiol (2020) low density lipoprotein cholesterol low density lipoprotein cholesterol measurement 223 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000115/ScoringFiles/PGS000115.txt.gz
PGS000192 GS9 PGP000079 Kathiresan S et al. N Engl J Med (2008) Cholesterol high density lipoprotein cholesterol measurement
low density lipoprotein cholesterol measurement
9 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000192/ScoringFiles/PGS000192.txt.gz
PGS000310 GRS194_LDL PGP000092 Xie T et al. Circ Genom Precis Med (2020) Low-density lipoprotein low density lipoprotein cholesterol measurement 194 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000310/ScoringFiles/PGS000310.txt.gz
PGS000340 LDL-Cpsp PGP000107 Trinder M et al. Circ Genom Precis Med (2020) Low-density lipoprotein cholesterol levels low density lipoprotein cholesterol measurement 28 http://ftp.ebi.ac.uk/pub/databases/spot/pgs/scores/PGS000340/ScoringFiles/PGS000340.txt.gz

PGS 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 ID)
Evaluated Score PGS Sample Set ID
(PSS ID)
Performance Source Trait PGS Effect Sizes
(per SD change)
PGS Classification Metrics Other Metrics Covariates Included in the Model PGS Performance: Other Relevant Information
PPM000155 PGS000061 (GRS_LDL) PSS000098 PGP000045
Johnson L et al. (2015)
Reported Trait: Serum low-density lipoprotein (LDL) levels β: 15.0 Beta (p-value): 0.0352 age, age^2, sex, GRS_HDL, GRS_TC, GRS_TG Association (p-value; unadjusted for covariates) < 0.001
PPM000156 PGS000061 (GRS_LDL) PSS000097 PGP000045
Johnson L et al. (2015)
Reported Trait: Serum low-density lipoprotein (LDL) levels β: 5.58 Beta (p-value): 0.697 age, age^2, sex, GRS_HDL, GRS_TC, GRS_TG Association (p-value; unadjusted for covariates) < 0.001
PPM000157 PGS000061 (GRS_LDL) PSS000096 PGP000045
Johnson L et al. (2015)
Reported Trait: Serum low-density lipoprotein (LDL) levels β: 30.04 Beta (p-value): 0.00282 age, age^2, sex, GRS_HDL, GRS_TC, GRS_TG Association (p-value; unadjusted for covariates) < 0.001
PPM000158 PGS000061 (GRS_LDL) PSS000099 PGP000045
Johnson L et al. (2015)
Reported Trait: Serum low-density lipoprotein (LDL) levels β: 42.86 Beta (p-value): 2e-05 age, age^2, sex, GRS_HDL, GRS_TC, GRS_TG Association (p-value; unadjusted for covariates) < 0.001
PPM000168 PGS000065 (GLGC2017_LDL) PSS000104 PGP000046
Kuchenbaecker K et al. (2019)
Reported Trait: Serum low-density lipoprotein (LDL) levels correlation (r): 0.274[0.254, 0.294] age, sex Relatedness and population structure were accounted for using a linear mixed model with random polygenic effect implemented in GEMMA
PPM000171 PGS000065 (GLGC2017_LDL) PSS000102 PGP000046
Kuchenbaecker K et al. (2019)
Reported Trait: Serum low-density lipoprotein (LDL) levels correlation (r): 0.229[0.172, 0.286] age, sex Relatedness and population structure were accounted for using a linear mixed model with random polygenic effect implemented in GEMMA
PPM000174 PGS000065 (GLGC2017_LDL) PSS000103 PGP000046
Kuchenbaecker K et al. (2019)
Reported Trait: Serum low-density lipoprotein (LDL) levels correlation (r): 0.29[0.231, 0.349] age, sex Relatedness and population structure were accounted for using a linear mixed model with random polygenic effect implemented in GEMMA
PPM000177 PGS000065 (GLGC2017_LDL) PSS000100 PGP000046
Kuchenbaecker K et al. (2019)
Reported Trait: Serum low-density lipoprotein (LDL) levels correlation (r): 0.28[0.257, 0.304] age, sex Relatedness and population structure were accounted for using a linear mixed model with random polygenic effect implemented in GEMMA
PPM000180 PGS000065 (GLGC2017_LDL) PSS000101 PGP000046
Kuchenbaecker K et al. (2019)
Reported Trait: Serum low-density lipoprotein (LDL) levels correlation (r): 0.198[0.161, 0.235] age, sex, region, 20 PCs of genetic ancestry Relatedness and population structure were accounted for using a linear mixed model with random polygenic effect implemented in GEMMA
PPM000563 PGS000192 (GS9) PSS000292 PGP000079
Kathiresan S et al. (2008)
Reported Trait: Incident cardiovascular event AUROC: 0.8 Hazard Ratio (HR; per allele): 1.15[1.07, 1.24] age, sex, family history of MI, LDL cholesterol, HDL cholesterol, triglycerides, blood pressure, body mass index, diabetes status, smoking status, CRP, lipid lowering medication
PPM000780 PGS000310 (GRS194_LDL) PSS000376 PGP000092
Xie T et al. (2020)
Reported Trait: Low-density lipoprotein (mmol/l) : 0.1849 Sex, age, age^2
PPM000264 PGS000115 (LDL-C_20) PSS000184 PGP000053
Trinder M et al. (2020)
Reported Trait: Serum low density lipoprotein cholesterol (LDL-C) levels β: 28.01 : 0.09 age, sex, 4 PCs of genetic ancestry, genotyping method (array and batch)
PPM000265 PGS000115 (LDL-C_20) PSS000183 PGP000053
Trinder M et al. (2020)
Reported Trait: Serum low density lipoprotein cholesterol (LDL-C) levels β: 21.73 : 0.06 age, sex, 4 PCs of genetic ancestry, genotyping method (array and batch)
PPM000266 PGS000115 (LDL-C_20) PSS000181 PGP000053
Trinder M et al. (2020)
Reported Trait: Serum low density lipoprotein cholesterol (LDL-C) levels β: 17.4 : 0.04 age, sex, 4 PCs of genetic ancestry, genotyping method (array and batch)
PPM000267 PGS000115 (LDL-C_20) PSS000185 PGP000053
Trinder M et al. (2020)
Reported Trait: Serum low density lipoprotein cholesterol (LDL-C) levels β: 27.78 : 0.09 age, sex, 4 PCs of genetic ancestry, genotyping method (array and batch)
PPM000268 PGS000115 (LDL-C_20) PSS000182 PGP000053
Trinder M et al. (2020)
Reported Trait: Cardiovascular disease events Hazard Ratio (HR; top vs. bottom decile of risk): 1.35[1.3, 1.4] age, sex, 4 PCs of genetic ancestry, genotyping method (array and batch)
PPM000562 PGS000192 (GS9) PSS000292 PGP000079
Kathiresan S et al. (2008)
Reported Trait: High-density lipoprotein (HDL) levels Association p-value: 2.00e-18
PPM000561 PGS000192 (GS9) PSS000292 PGP000079
Kathiresan S et al. (2008)
Reported Trait: Low-density lipoprotein (LDL) levels Association p-value: 3.00e-24
PPM000924 PGS000340 (LDL-Cpsp) PSS000466 PGP000107
Trinder M et al. (2020)
Reported Trait: Low-density lipoprotein cholesterol levels β: 0.82 : 0.074 Age, sex
PPM000923 PGS000340 (LDL-Cpsp) PSS000465 PGP000107
Trinder M et al. (2020)
Reported Trait: Low-density lipoprotein cholesterol levels in familial hypercholesterolemia mutation carriers Beta (per 20% increase in PGS): 0.13[0.072, 0.19]
PPM000925 PGS000340 (LDL-Cpsp) PSS000465 PGP000107
Trinder M et al. (2020)
Reported Trait: Atherosclerotic cardiovascular disease in familial hypercholesterolemia mutation carriers Odds Ratio (OR; top 20% vs. rest): 1.48[1.02, 2.14] sex

Evaluated Samples

PGS Sample Set ID
(PSS ID)
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
PSS000465 Individuals ≥18 years with clinically diagnosed heterozygous familial hypercholesterolemia (FH) from the BCFH cohort. Individuals who were positive for the common French Canadian variant in the LDLR gene including del.15 kb of the promoter and exon 1, del.5 kb of exons 2 and 3, p.W66G (exon 3), p.E207K (exon 4), p.Y468X (exon 10), or p.C646Y (exon 14) in this study. Fasting clinical lipid profiles were obtained following a 4-week washout of any cholesterol-lowering medications from the CNMA cohort. Individuals who were positive for a LDLR, APOB, or PCSK9 variant that was deemed to cause FH in the UKB cohort.Any atherosclerotic cardiovascular disease (ASCVD) event, which was defined as myocardial infarction, coronary artery disease or carotid revascularization, transient ischemic attack or stroke. For the UK Biobank, retrospecitvie ASCVD was self reported and prospective ASCVD were defined using hospital episode statistics and 10th revision of the International Statistical Classification of Diseases and Related Health Problems diagnosis codes and OPCS Classification of Interventions and Procedures version 4 procedure codes 1,120 individuals,
40.4 % Male samples
Mean = 41.36 years European, NR European (94%), Not reported (6%) BCFH, CNMA, UKB
PSS000466 Any atherosclerotic cardiovascular disease (ASCVD) event, which was defined as myocardial infarction, coronary artery disease or carotid revascularization, transient ischemic attack or stroke. For the UK Biobank, retrospecitvie ASCVD was self reported and prospective ASCVD were defined using hospital episode statistics and 10th revision of the International Statistical Classification of Diseases and Related Health Problems diagnosis codes and OPCS Classification of Interventions and Procedures version 4 procedure codes 389,127 individuals European UKB
PSS000292 Composite end point of cardiovascular events was defined as myocardial infarction, ischemic stroke, and death from coronary heart disease. Death from coronary heart disease was defined on the basis of codes 412 and 414 (ICD-9) or I22–I23 and I25 (ICD-10) in the Swedish Cause of Death Register. Myocardial infarction was defined on the basis of codes 410 and I21 in the International Classification of Diseases, 9th Revision and 10th Revision (ICD-9 and ICD-10), respectively. Ischemic stroke was defined on the basis of codes 434 or 436 (ICD-9) and I63 or I64 (ICD-10). Median = 10.6 years
[
  • 238 cases
  • , 3,994 controls
]
European MDC
PSS000376 We measured weight and height using regularly calibrated equipment (scales and stadiometer models 770 and 214, respectively; Seca, Hamburg, Germany). Body mass index (BMI; in kg/m2) was also calculated. We measured waist circumference at the midpoint between the lower costal margin and the iliac crest. The hip circumference was measured over both trochanter majores (tangible bone on the outside of the hip joint). Waist to hip ratio was also calculated. We performed all measurements in duplicate, and, if the difference between these measurements exceeded a predefined value, a third measurement was performed. All available measurements were used to calculate means. Heart rate, systolic (SBP) and diastolic (DBP) blood pressure were measured in duplicate with a Dinamap Critikon 1846SX (Critikon Inc, Tampa, FL), from which we calculated means. At the third visit, fasting blood sample of participants were drawn for the measurement of glucose (Roche Diagnostics, Basel, Switzerland), insulin (Diagnostic Systems Laboratories Inc, Webster, TX), HbA1c (high performance liquid chromatography, Variant, Bio-Rad), triglycerides, total cholesterol, HDL cholesterol (Roche Diagnostics) and LDL cholesterol (calculated according to Friedewald’s equation5), as well as alanine transaminase (Photometric determination according to the reference method of the International Federation of Clinical Chemistry (IFCC)6) and lipoprotein(a) (Nephelometric method, BN2, DadeBehring). Serum creatinine was measured by photometric determination with the Jaffé method without deproteinisation (Ecoline® MEGA, DiaSys Diagnostic Systems GmbH. Merck). eGFR for adolescents who were younger than 18 years old was calculated using the Schwartz formula.7 High‐sensitivity C‐reactive protein (hsCRP) was determined using an immunonephelometric method, BN2 (CardioPhase hsCRP, Siemens) with a lower detection limit of 0.175 mg/L. Total IgE measurements were performed using the Phadia Immunocap 100 system with fluoroenzyme immunoassay (FEIA). 1,354 individuals,
47.56 % Male samples
Mean = 16.22 years
Sd = 0.66 years
European TRAILS
PSS000096 Lipid levels are represented in mg/dL, individuals on any lipid-lowering medication (n = 1,018) were omitted from all analyses. 1,355 individuals,
46.2 % Male samples
Mean = 61.68 years African American or Afro-Caribbean MESA MESA Classic Cohort
PSS000097 Lipid levels are represented in mg/dL, individuals on any lipid-lowering medication (n = 1,018) were omitted from all analyses. 666 individuals,
50.15 % Male samples
Mean = 61.5 years East Asian MESA MESA Classic Cohort
PSS000098 Lipid levels are represented in mg/dL, individuals on any lipid-lowering medication (n = 1,018) were omitted from all analyses. 2,063 individuals,
46.78 % Male samples
Mean = 62.09 years European MESA MESA Classic Cohort
PSS000099 Lipid levels are represented in mg/dL, individuals on any lipid-lowering medication (n = 1,018) were omitted from all analyses. 1,256 individuals,
48.89 % Male samples
Mean = 60.65 years Hispanic or Latin American MESA MESA Classic Cohort
PSS000100 Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides (TG) 6,407 individuals,
44.0 % Male samples
Mean = 34.0 years Sub-Saharan African APCDR APCDR-Uganda study
PSS000101 Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides (TG) 21,295 individuals,
38.0 % Male samples
Mean = 60.0 years East Asian
(Chinese)
CKB - 20810 samples had HDL measurements - 17662 samples had LDL measurements - 20222 samples had triglyceride measurements
PSS000102 Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides (TG) 1,641 individuals,
58.0 % Male samples
Mean = 62.0 years European
(Greek)
Population isolate from the Pomak villages in the North of Greece HELIC - 1186 samples had HDL measurements - 1186 samples had LDL measurements - 1176 samples had triglyceride measurements
PSS000103 Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides (TG) 1,945 individuals,
66.0 % Male samples
Mean = 45.0 years European
(Greek)
Population isolate from the Mylopotamos villages in Crete HELIC - 1078 samples had HDL measurements - 1075 samples had LDL measurements - 1066 samples had triglyceride measurements
PSS000104 Serum levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol and triglycerides (TG) 9,962 individuals,
56.0 % Male samples
Mean = 52.0 years European UKHLS - 9706 samples had HDL measurements - 9767 samples had LDL measurements - 9635 samples had triglyceride measurements
PSS000181 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 4,680 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
African unspecified UKB Genotyping Array Cohort
PSS000182 Cardiovascular disease events were defined as coronary and carotid revascularization, myocardial infarction, ischemic stroke, and all-cause mortality. The CVD events occurring before and after enrollment were included. Events occurring prior to enrollment were identified by either self-reported medical history and/or previous hospital admission documented in an electronic health record.
[
  • 5,397 cases
  • , 42,448 controls
]
,
43.36 % Male samples
Mean = 56.64 years
Sd = 7.99 years
Other Combined analysis of European, East Asian and African unspecified  UKB Genotyping Array & Exome Sequencing Cohort
PSS000183 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 10,640 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
East Asian UKB Genotyping Array Cohort
PSS000184 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 439,871 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
European UKB Genotyping Array Cohort
PSS000185 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 439,871 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
European UKB Genotyping Array Cohort
PSS000185 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 10,640 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
East Asian UKB Genotyping Array Cohort
PSS000185 LDL-C serum biochemistry was desribed previously (http://biobank.ndph.ox.ac.uk/showcase/showcase/docs/serum_biochemistry.pdf). 4,680 individuals,
45.8 % Male samples
Mean = 56.6 years
Sd = 8.1 years
African unspecified UKB Genotyping Array Cohort