| Title: | A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry |
| Journal: | Hepatology Communications |
| Published: | 10 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38727677/ |
| DOI: | https://doi.org/10.1097/hc9.0000000000000431 |
| Citations: | 1 (1 in last 2 years) as of 8 Aug 2024 |
Publication 12110
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Abstract
BACKGROUND: Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.</p>
METHODS: Using a data-driven approach, a PRS for ALC was generated using a meta-genome-wide association study of ALC (N=4305) and an independent cohort of heavy drinkers with ALC and without significant liver disease (N=3037). It was validated in 2 additional independent cohorts from the UK Biobank with diagnosed ALC (N=467) and high-risk drinking controls (N=8981) and participants in the Indiana Biobank Liver cohort with alcohol-associated liver disease (N=121) and controls without liver disease (N=3239).</p>
RESULTS: A 20-single-nucleotide polymorphisms PRS for ALC (PRSALC) was generated that stratified risk for ALC comparing the top and bottom deciles of PRS in the 2 validation cohorts (ORs: 2.83 [95% CI: 1.82 -4.39] in UK Biobank; 4.40 [1.56 -12.44] in Indiana Biobank Liver cohort). Furthermore, PRSALC improved the prediction of ALC risk when added to the models of clinically known predictors of ALC risk. It also stratified the risk for metabolic dysfunction -associated steatotic liver disease -cirrhosis (3.94 [2.23 -6.95]) in the Indiana Biobank Liver cohort -based exploratory analysis.</p>
CONCLUSIONS: PRSALC incorporates 20 single-nucleotide polymorphisms, predicts increased risk for ALC, and improves risk stratification for ALC compared with the models that only include clinical risk factors. This new score has the potential for early detection of heavy drinking patients who are at high risk for ALC.</p>
43 Authors
- Tae-Hwi Schwantes-An
- John B. Whitfield
- Guruprasad P. Aithal
- Stephen R. Atkinson
- Ramon Bataller
- Greg Botwin
- Naga P. Chalasani
- Heather J. Cordell
- Ann K. Daly
- Rebecca Darlay
- Christopher P. Day
- Florian Eyer
- Tatiana Foroud
- Samer Gawrieh
- Dermot Gleeson
- David Goldman
- Paul S. Haber
- Jean-Marc Jacquet
- Craig S. Lammert
- Tiebing Liang
- Suthat Liangpunsakul
- Steven Masson
- Philippe Mathurin
- Romain Moirand
- Andrew McQuillin
- Christophe Moreno
- Marsha Y. Morgan
- Sebastian Mueller
- Beat Müllhaupt
- Laura E. Nagy
- Pierre Nahon
- Bertrand Nalpas
- Sylvie Naveau
- Pascal Perney
- Munir Pirmohamed
- Helmut K. Seitz
- Michael Soyka
- Felix Stickel
- Andrew Thompson
- Mark R. Thursz
- Eric Trépo
- Timothy R. Morgan
- Devanshi Seth
1 Application
| Application ID | Title |
|---|---|
| 18870 | Genetics of alcoholic liver cirrhosis |
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