| Predicted Trait | |
| Reported Trait | Cirrhosis |
| Mapped Trait(s) | cirrhosis of liver (EFO_0001422) |
| Score Construction | |
| PGS Name | GRS9_Cirr |
| Development Method | |
| Name | Variants significantly associated with alcohol-related cirrhosis |
| Parameters | FDR < 20% |
| Variants | |
| Original Genome Build | NR |
| Number of Variants | 9 |
| Effect Weight Type | beta |
| PGS Source | |
| PGS Catalog Publication (PGP) ID | PGP000180 |
| Citation (link to publication) | Innes H et al. Gastroenterology (2020) |
| Study Identifiers | Sample Numbers | Sample Ancestry | Cohort(s) |
|---|---|---|---|
GWAS Catalog: GCST90011734 Europe PMC: 32561361 |
33,437 individuals | European | UKB |
GWAS Catalog: GCST90011735 Europe PMC: 32561361 |
33,330 individuals | European | UKB |
GWAS Catalog: GCST90011736 Europe PMC: 32561361 |
33,324 individuals | European | UKB |
GWAS Catalog: GCST90011737 Europe PMC: 32561361 |
34,101 individuals | European | UKB |
GWAS Catalog: GCST90011738 Europe PMC: 32561361 |
34,238 individuals | European | UKB |
| Study Identifiers | Sample Numbers | Sample Ancestry | Cohort(s) | Phenotype Definitions & Methods | Age of Study Participants | Participant Follow-up Time | Additional Ancestry Description | Additional Sample/Cohort Information |
|---|---|---|---|---|---|---|---|---|
| — | 2,068 individuals | European | NR | Cases were individuals with alcohol-related cirrhosis. Participants were defined as cases if they fulfilled one of the following criteria: (1) presence of cirrhosis on liver biopsy specimen (Ishak’s fibrosis stage 5 or 6) or (2) unequivocal clinical and laboratory evidence for the presence of cirrhosis as reflected by a combination of (a) abnormal standard liver function tests (serum transaminases, γ-glutamyl transpeptidase, albumin, prothrombin time, international normalized ratio, and platelet count), (b) cirrhosis-related complications, including encephalopathy or ascites, (c) findings on imaging compatible with a diagnosis of cirrhosis (distorted liver surface, ascites, splenomegaly, collateral circulation), and (d) detection of esophageal varices on upper gastrointestinal endoscopy. | — | — | — | Phase 2 replication analysis dataset used to select SNPs for GRS. Case/control breakdown not provided. |
| — | 2,545 individuals | European (British, English, Scottish, Welsh, Irish, German) |
UKB | Cases were individuals with alcohol-related cirrhosis. For participants from Buch et al's UK cohort cases had evidence of cirrhosis on histologic examination of liver biopsy tissue. From Buch et al's German cohort, participants were defined as cases if they fulfilled one of the following criteria: (1) presence of cirrhosis on liver biopsy specimen (Ishak’s fibrosis stage 5 or 6) or (2) unequivocal clinical and laboratory evidence for the presence of cirrhosis as reflected by a combination of (a) abnormal standard liver function tests (serum transaminases, γ-glutamyl transpeptidase, albumin, prothrombin time, international normalized ratio, and platelet count), (b) cirrhosis-related complications, including encephalopathy or ascites, (c) findings on imaging compatible with a diagnosis of cirrhosis (distorted liver surface, ascites, splenomegaly, collateral circulation), and (d) detection of esophageal varices on upper gastrointestinal endoscopy. Participants from Germany and Switzerland were independently diagnosed as alcohol dependent, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria by 2 psychiatrists. For the UKB cohort, cases were defined with (a) ≥2 hospital admissions for alcohol-related cirrhosis before or after inclusion in the UKB study, (defined as International Classification of Diseases 10th Revision [ICD 10]: K70.3 in any diagnostic position); or (b) death from alcohol-related cirrhosis (defined as ICD 10: K703 in any cause-of-death position). | — | — | — | Phase 1 replication/validation analysis dataset used to obtain weights for each SNP within the GRS. Additional cases and controls were obtained from a UK cohort and a German cohort described by Buch et al (PMID: 26482880). Case/control breakdown not provided. |
|
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 |
|---|---|---|---|---|---|---|---|---|
| PPM002011 | PSS000996| Ancestry Not Reported| 107,014 individuals |
PGP000180 | Innes H et al. Gastroenterology (2020) |
Reported Trait: Incident liver cirrhosis in individuals at-risk for nonalcoholic fatty liver disease (time to first hospitilisation) | — | C-index: 0.62 [0.59, 0.64] | Hazard Ratio (HR, top 20% vs bottom 20%): 3.12 [2.37, 4.12] | — | — |
| PPM002012 | PSS000996| Ancestry Not Reported| 107,014 individuals |
PGP000180 | Innes H et al. Gastroenterology (2020) |
Reported Trait: Incident liver cirrhosis in individuals at-risk for nonalcoholic fatty liver disease (time to first hospitilisation) | — | — | Hazard Ratio (HR, top 20% vs bottom 20%): 3.16 [2.38, 4.21] | Age, sex, BMI, diabetes, units of alcohol consumed per week | — |
| PPM002013 | PSS000996| Ancestry Not Reported| 107,014 individuals |
PGP000180 | Innes H et al. Gastroenterology (2020) |
Reported Trait: Incident liver cirrhosis in individuals at-risk for nonalcoholic fatty liver disease (time to first hospitilisation) | — | C-index: 0.677 [0.653, 0.7] | — | Age, sex | — |
|
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 |
|---|---|---|---|---|---|---|---|---|
| PSS000996 | All individuals (cases and controls) met the at-risk criteria for nonalcoholic fatty liver disease (NAFLD) defined as a BMI ≥30 kg/m2 or diagnosis of type 2 diabetes, or both, without evidence of any other cause of liver disease including excess alcohol . Cases were individuals who had been hospitalised with cirrhosis for the first time. A hospital admission for cirrhosis was defined according to the Ratib et al (PMID: 24419483) validated algorithm incorporating appropriate ICD discharge codes and OPCS Classification of Interventions and Procedures version 4 codes. | Mean = 7.9 years | [ ,
43.0 % Male samples |
Median = 59.0 years Range = [52.0, 64.0] years |
Not reported | — | UKB | GRS dataset used to test/ evaluate performance of GRS. The GRS dataset is independent of the discovery analysis datasets containing UKB participants. Possible sample overlap between the GRS dataset and the phase 1 replication/validation analysis and phase 2 replication analysis datasets containing UKB participants. |