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Article Dans Une Revue Hepatology Communications Année : 2024

A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry

1 IUPUI - Indiana University - Purdue University Indianapolis
2 QIMR Berghofer Medical Research Institute
3 UON - University of Nottingham, UK
4 Imperial College London
5 UPMC - University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis]
6 Cedars-Sinai Medical Center
7 VA Long Beach Healthcare System - Veterans Affairs Long Beach Healthcare System
8 Newcastle University [Newcastle]
9 TUM - Technische Universität Munchen - Technical University Munich - Université Technique de Munich
10 MRI TUM - Klinikum rechts der Isar
11 Sheffield Teaching Hospitals NHS Foundation Trust [Sheffield, Royaume-Uni]
12 NIAAA - National Institute on Alcohol Abuse and Alcoholism [Bethesda, MD, USA]
13 The University of Sydney
14 Sydney Local Health District
15 CHU Nîmes - Hôpital Universitaire Carémeau [Nîmes]
16 Roudebush Veterans Administration Medical Center Indiana
17 Hôpital Claude Huriez [Lille]
18 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
19 Centre Hospitalier Universitaire [Rennes]
20 NuMeCan - Nutrition, Métabolismes et Cancer
21 UCL - University College of London [London]
22 ULB - Université libre de Bruxelles
23 Hôpital Erasme [Bruxelles]
24 Universität Heidelberg [Heidelberg] = Heidelberg University
25 University hospital of Zurich [Zurich]
26 Lerner Research Institute [Cleveland, OH, USA]
27 Hôpital Avicenne [AP-HP]
28 FunGeST - Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors [CRC]
29 DISC/IST - Information Scientifique et Technique
30 AP-HP - Hôpital Antoine Béclère [Clamart]
31 Royal Liverpool and Broadgreen University Hospital NHS Trust
32 University of Liverpool
33 University-Hospital Munich-Großhadern [München]
34 UC Irvine - University of California [Irvine]
Stephen R Atkinson
Heather Cordell
Ann K. Daly
Rebecca Darlay
Christopher P. Day
Steven Masson
Andrew Mcquillin
Marsha y Morgan
Beat Müllhaupt
Pascal Perney
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Résumé

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. 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). 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. 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.
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hal-04574724 , version 1 (24-05-2024)

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Tae-Hwi Schwantes-An, John Whitfield, Guruprasad P. Aithal, Stephen R Atkinson, Ramon Bataller, et al.. A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry. Hepatology Communications, 2024, 8 (6), pp.e0431. ⟨10.1097/hc9.0000000000000431⟩. ⟨hal-04574724⟩
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