Polygenic Score (PGS) ID: PGS000865

Predicted Trait
Reported Trait Hepatic fat content
Mapped Trait(s) liver fat measurement (EFO_0010821)
Released in PGS Catalog: Aug. 26, 2021
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Score Details

Score Construction
PGS Name PRS-HFC
Development Method
Name Variants with validated effects on hepatic fat accumulation and/or nonalcoholic fatty liver disease severity and with experimental data supporting the casuality of the association
Parameters NR
Variants
Original Genome Build NR
Number of Variants 4
Effect Weight Type beta
PGS Source
PGS Catalog Publication (PGP) ID PGP000212
Citation (link to publication) Dongiovanni P et al. J Intern Med (2017)
Ancestry Distribution
Source of Variant
Associations (GWAS)
European: 65.2%
African: 19.9%
East Asian: 7.6%
Hispanic or Latin American: 6.5%
Not Reported: 0.8%
17,458 individuals (100%)
Score Development/Training
Multi-ancestry (including European): 100%
  • European
  • African
  • Hispanic or Latin American
2,736 individuals (100%)
PGS Evaluation
European: 81.8%
Not Reported: 9.1%
Multi-ancestry (including European): 9.1%
  • European
  • African
  • Hispanic or Latin American
  • Not Reported
11 Sample Sets

Development Samples

Source of Variant Associations (GWAS)
Study Identifiers Sample Numbers Sample Ancestry Cohort(s)
Europe PMC: 18820647
1,032 individuals African American or Afro-Caribbean DaHS
Europe PMC: 18820647
696 individuals European DaHS
Europe PMC: 18820647
383 individuals Hispanic or Latin American DaHS
GWAS Catalog: GCST001008
Europe PMC: 21423719
7,176 individuals European AGES, AMISH, FHS, FamHS
GWAS Catalog: GCST010096
Europe PMC: 24531328
2,448 individuals African American or Afro-Caribbean DaHS
GWAS Catalog: GCST010096
Europe PMC: 24531328
1,365 individuals European DaHS
GWAS Catalog: GCST010096
Europe PMC: 24531328
753 individuals Hispanic or Latin American DaHS
GWAS Catalog: GCST010096
Europe PMC: 24531328
141 individuals Not reported DaHS
GWAS Catalog: GCST003153
Europe PMC: 26482880
2,138 individuals European NR
GWAS Catalog: GCST001928
Europe PMC: 23535911
1,326 individuals East Asian NR
Score Development/Training
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
2,736 individuals European, African American or Afro-Caribbean, Hispanic or Latin American DaHS

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
PPM002444 PSS001102|
European Ancestry|
356,820 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma in individuals with no cirrhosis OR: 1.8 [1.1, 3.1] AUROC: 0.55 Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre PRS-HFC was treated as a binary variable with a cutoff of ≥0.532
PPM002426 PSS001096|
European Ancestry|
364,048 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 11.1 [6.1, 20.2] Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre
PPM002427 PSS001096|
European Ancestry|
364,048 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 4.6 [2.5, 8.6] Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre, diagnosis of cirrhosis
PPM002423 PSS001096|
European Ancestry|
364,048 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Cirrhosis OR: 4.1 [3.2, 5.1]
PPM002424 PSS001100|
European Ancestry|
358,314 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 11.1 [6.1, 20.4]
PPM002425 PSS001096|
European Ancestry|
364,048 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Cirrhosis OR: 4.2 [3.3, 5.3] Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre
PPM002434 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Fatty liver disease OR: 8.4 [5.7, 12.5]
PPM002435 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Severe fibrosis in individuals within stage F3-F4 of fatty liver disease OR: 11.4 [7.4, 17.7]
PPM002436 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 9.2 [5.2, 16.3]
PPM002437 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Fatty liver disease OR: 10.1 [6.2, 16.5] Age, sex, body mass index, type 2 diabetes
PPM002438 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Severe fibrosis in individuals within stage F3-F4 of fatty liver disease OR: 7.5 [4.3, 13.0] Age, sex, body mass index, type 2 diabetes
PPM002439 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 3.0 [1.4, 6.4] Age, sex, body mass index, type 2 diabetes
PPM002441 PSS001094|
European Ancestry|
2,564 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 3.0 [2.2, 3.9] AUROC: 0.64 Age, sex, body mass index, type 2 diabetes
PPM002442 PSS001100|
European Ancestry|
358,314 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 3.3 [2.4, 4.5] AUROC: 0.63 Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre PRS-HFC was treated as a binary variable with a cutoff of ≥0.532
PPM002446 PSS001099|
European Ancestry|
86,204 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma in individuals with a body mass index ≥30 OR: 5.2 [3.4, 8.1] AUROC: 0.69 Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre PRS-HFC was treated as a binary variable with a cutoff of ≥0.532
PPM002448 PSS001104|
European Ancestry|
25,132 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma in individuals with type 2 diabetes OR: 4.4 [2.7, 6.9] AUROC: 0.7 Age, sex, body mass index, type 2 diabetes, PCs(1-10), array batch, assessment centre PRS-HFC was treated as a binary variable with a cutoff of ≥0.532
PPM002450 PSS001095|
Ancestry Not Reported|
429 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 8.68 [3.2, 23.5] AUROC: 0.64
PPM002408 PSS001089|
Multi-ancestry (including European)|
4,570 individuals
PGP000212 |
Dongiovanni P et al. J Intern Med (2017)
Reported Trait: Steatosis : 0.035 Only 4,455 of the 4,570 individuals from DaHS were utilised as they had available genotype, phenotype and covariate data.
PPM002409 PSS001089|
Multi-ancestry (including European)|
4,570 individuals
PGP000212 |
Dongiovanni P et al. J Intern Med (2017)
Reported Trait: Alanine aminotransferase levels Association p-value (<): 0.001 Age, sex, ethnicity, body mass index, statin use Only 4,455 of the 4,570 individuals from DaHS were utilised as they had available genotype, phenotype and covariate data.
PPM002473 PSS001114|
European Ancestry|
266,687 individuals
PGP000217 |
De Vincentis A et al. Clin Gastroenterol Hepatol (2021)
|Ext.
Reported Trait: Incident severe liver disease HR: 1.25 [1.16, 1.35] Hazard Ratio (HR, top 25% vs bottom 25%): 1.63 [1.28, 2.08] Age, sex
PPM002474 PSS001115|
European Ancestry|
13,268 individuals
PGP000217 |
De Vincentis A et al. Clin Gastroenterol Hepatol (2021)
|Ext.
Reported Trait: Incident severe liver disease in individuals with diabetes HR: 1.55 [1.33, 1.8] Hazard Ratio (HR, top 25% vs bottom 25%): 3.24 [1.93, 5.43] Age, sex
PPM002475 PSS001116|
European Ancestry|
64,655 individuals
PGP000217 |
De Vincentis A et al. Clin Gastroenterol Hepatol (2021)
|Ext.
Reported Trait: Incident severe liver disease in obese individuals HR: 1.4 [1.25, 1.57] Hazard Ratio (HR, top 25% vs bottom 25%): 2.29 [1.6, 3.29] Age, sex
PPM002476 PSS001114|
European Ancestry|
266,687 individuals
PGP000217 |
De Vincentis A et al. Clin Gastroenterol Hepatol (2021)
|Ext.
Reported Trait: Incident severe liver disease in individuals with a fatty liver index ≥ 60 HR: 1.34 [1.23, 1.47] Hazard Ratio (HR, top 25% vs bottom 25%): 2.13 [1.57, 2.89] Age, sex
PPM002452 PSS001095|
Ancestry Not Reported|
429 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 6.56 [1.54, 17.39] Age, sex, body mass index, type 2 diabetes
PPM002454 PSS001095|
Ancestry Not Reported|
429 individuals
PGP000215 |
Bianco C et al. J Hepatol (2020)
|Ext.
Reported Trait: Hepatocellular carcinoma OR: 2.32 [1.16, 4.66] PRS-HFC was treated as a binary variable with a cutoff of ≥0.532

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
PSS001104 All individuals had type 2 diabetes (T2D). Diabetes was defined as individuals having either of following criteria: 1) self-reported type 2 or unspecified diabetes (codes 1220 and 1223 in data-field 20002); 2) ICD10 diagnoses codes E11 and E14 (data-field 41270); 3) insulin treatment or use of oral glucose lowering drugs (data-fields 6153, 6177 and 20003); 4) serum glucose level ≥11.1 mmol/L (200mg/dL); 5) HbA1c ≥ 48 mmol/mol (6.5%). Cases were individuals with hepatocellular cancer (HCC). HCC was defined by combining International Classification of Diseases, Tenth Revision (ICD-10) code C22.0 from both UK cancer registry (data-field 40006), and hospitalization records (data-field 41270).
[
  • 81 cases
  • , 25,051 controls
]
European UKB
PSS001089 Plasma levels of lipids and lipoproteins were measured by standard enzymatic assays. Hypertension was defined as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg, or self‐reported antihypertensive treatment. Of the 4,570 individuals, 1,496 had hypertension. 4,570 individuals,
43.0 % Male samples
Mean = 45.0 years
Sd = 11.0 years
European, African American or Afro-Caribbean, Hispanic or Latin American, Not reported European = 1,351, African American or Afro-Caribbean = 2,355, Hispanic or Latin American = 743, Not reported = 121 DaHS 40.12% sample overlap with this dataset and the dataset used to develop PRS-HFC.
PSS001114 Cases were individuals with severe liver disease (SLD). SLD was defined as a composite diagnosis of cirrhosis, decompensated liver disease (i.e., esophageal varices with or without bleeding, portal hypertension, hepatorenal syndrome, liver failure), hepatocellular carcinoma and/or liver transplantation (ICD-10 C22.0, I85.0, I85.9, K70.3, K70.4, K72.1, K72.9, K74.1, K74.2, K74.6, K76.6, K76.7, Z94.4) in any of the aforementioned records. Median = 9.0 years
Iqr = [8.3, 9.7] years
[
  • 543 cases
  • , 266,144 controls
]
,
45.0 % Male samples
Mean = 56.5 years
Sd = 8.1 years
European UKB
PSS001115 All individuals had diabetes. Cases were individuals with severe liver disease (SLD). SLD was defined as a composite diagnosis of cirrhosis, decompensated liver disease (i.e., esophageal varices with or without bleeding, portal hypertension, hepatorenal syndrome, liver failure), hepatocellular carcinoma and/or liver transplantation (ICD-10 C22.0, I85.0, I85.9, K70.3, K70.4, K72.1, K72.9, K74.1, K74.2, K74.6, K76.6, K76.7, Z94.4) in any of the aforementioned records.
[
  • 125 cases
  • , 13,143 controls
]
European UKB
PSS001116 All individuals were classified as obese. Cases were individuals with severe liver disease (SLD). SLD was defined as a composite diagnosis of cirrhosis, decompensated liver disease (i.e., esophageal varices with or without bleeding, portal hypertension, hepatorenal syndrome, liver failure), hepatocellular carcinoma and/or liver transplantation (ICD-10 C22.0, I85.0, I85.9, K70.3, K70.4, K72.1, K72.9, K74.1, K74.2, K74.6, K76.6, K76.7, Z94.4) in any of the aforementioned records.
[
  • 238 cases
  • , 64,417 controls
]
European UKB
PSS001094 Cases were individuals with liver disease. Of the 1,699 cases, 1,473 had fatty liver disease (FLD) whilst 226 had hepatocellular carcinoma (HCC). Of the 1,473 individuals with FLD, 297 had severe fibrosis and were therefore classified as being within stage 3-4 of FLD. Severe fibrosis was defined in the presence of histological fibrosis F3-F4 (when liver biopsy was available) or in presence of clinical, endoscopic or radiological signs of portal hypertension or cirrhosis, or liver stiffness ≥8.4 kPa evaluated by Fibroscan. Diagnosis of HCC was based on EASL-EORTC Clinical Practice Guidelines.
[
  • 1,699 cases
  • , 865 controls
]
,
57.76 % Male samples
European NR Cases were obtained from the Nonalcoholic Fatty Liver Disease (NAFLD) Case-Control Cross-Sectional Cohort.
PSS001095 All individuals had liver disease. Of the 158 cases, 72 had cirrhosis whilst 84 had hepatocellular cancer. Diagnosis of HCC was based on EASL-EORTC Clinical Practice Guidelines
[
  • 158 cases
  • , 271 controls
]
,
43.59 % Male samples
Not reported NR
PSS001096 Cases were individuals with liver disease. Of the 1,628 cases, 1,426 individuals had cirrhosis whilst 202 had hepatocellular cancer (HCC). Cirrhosis was defined as ICD-10 codes I85.0, I85.9, K70.3, K70.4, K72.1, K74.1, K74.2, K74.6, K76.6, K76.7 using hospitalization records (data-field 41270). HCC was defined by combining International Classification of Diseases, Tenth Revision (ICD-10) code C22.0 from both UK cancer registry (data-field 40006), and hospitalization records (data-field 41270).
[
  • 1,628 cases
  • , 362,420 controls
]
,
46.22 % Male samples
European UKB
PSS001099 All individuals had a body mass index ≥30. Cases were individuals with hepatocellular cancer (HCC). HCC was defined by combining International Classification of Diseases, Tenth Revision (ICD-10) code C22.0 from both UK cancer registry (data-field 40006), and hospitalization records (data-field 41270).
[
  • 88 cases
  • , 86,116 controls
]
European UKB
PSS001100 Cases were individuals with hepatocellular cancer (HCC). HCC was defined by combining International Classification of Diseases, Tenth Revision (ICD-10) code C22.0 from both UK cancer registry (data-field 40006), and hospitalization records (data-field 41270).
[
  • 188 cases
  • , 358,126 controls
]
European UKB
PSS001102 All individuals had no diagnosis of cirrhosis. Cases were individuals with hepatocellular cancer (HCC). HCC was defined by combining International Classification of Diseases, Tenth Revision (ICD-10) code C22.0 from both UK cancer registry (data-field 40006), and hospitalization records (data-field 41270).
[
  • 95 cases
  • , 356,725 controls
]
European UKB