| Title: |
A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry |
| Authors: |
Schwantes-An, Tae-Hwi; Whitfield, John; Aithal, Guruprasad P.; Atkinson, Stephen R; Bataller, Ramon; Botwin, Greg; Chalasani, Naga P; Cordell, Heather; Daly, Ann K.; Darlay, Rebecca; Day, Christopher P.; Eyer, Florian; Foroud, Tatiana; Gawrieh, Samer; Gleeson, Dermot; Goldman, David; Haber, Paul S; Jacquet, Jean-Marc; S. Lammert, Craig; Liang, Tiebing; Liangpunsakul, Suthat; Masson, Steven; Mathurin, Philippe; Moirand, Romain; Mcquillin, Andrew; Moreno, Christophe; Morgan, Marsha y; Mueller, Sebastian; Müllhaupt, Beat; Nagy, Laura; Nahon, Pierre; Nalpas, Bertrand; Naveau, Sylvie; Perney, Pascal; Pirmohamed, Munir; Seitz, Helmut K.; Soyka, Michael; Stickel, Felix; Thompson, Andrew; Thursz, Mark R; Trépo, Eric; Morgan, Timothy, R.; Seth, Devanshi |
| Contributors: |
Indiana University - Purdue University Indianapolis (IUPUI); Indiana University System; QIMR Berghofer Medical Research Institute; University of Nottingham, UK (UON); Imperial College London; University of Pittsburgh Medical Center Pittsburgh, PA, États-Unis (UPMC); Cedars-Sinai Medical Center; Veterans Affairs Long Beach Healthcare System (VA Long Beach Healthcare System); Newcastle University Newcastle; Technische Universität Munchen - Technical University Munich - Université Technique de Munich (TUM); Klinikum rechts der Isar (MRI TUM); Sheffield Teaching Hospitals NHS Foundation Trust Sheffield, Royaume-Uni; National Institute on Alcohol Abuse and Alcoholism Bethesda, MD, USA (NIAAA); The University of Sydney; Sydney Local Health District; Hôpital Universitaire Carémeau Nîmes (CHU Nîmes); Centre Hospitalier Universitaire de Nîmes (CHU Nîmes); Roudebush Veterans Administration Medical Center Indiana; Hôpital Claude Huriez Lille; Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Institute for Translational Research in Inflammation - U 1286 (INFINITE); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire CHU Lille (CHRU Lille); Centre Hospitalier Universitaire Rennes; Nutrition, Métabolismes et Cancer (NuMeCan); Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); University College of London London (UCL); Université libre de Bruxelles (ULB); Hôpital Erasme = Erasmus Hospital = Erasmus Ziekenhuis (HUB-ULB); Universität Heidelberg Heidelberg = Heidelberg University; University hospital of Zurich Zurich; Lerner Research Institute Cleveland, OH, USA; Cleveland Clinic; Hôpital Avicenne AP-HP; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP); Génomique fonctionnelle des tumeurs solides = Functional Genomics of Solid Tumors CRC (FunGeST); Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)); École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE); Université Paris Sciences et Lettres (PSL)-Université Paris Sciences et Lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité); Information Scientifique et Technique (DISC/IST); Institut National de la Santé et de la Recherche Médicale (INSERM); AP-HP - Hôpital Antoine Béclère Clamart; Royal Liverpool and Broadgreen University Hospital NHS Trust; University of Liverpool; University-Hospital Munich-Großhadern München; University of California Irvine (UC Irvine); University of California (UC); Funding for this study was provided by NIH/NIAAA UO1AA018389 and RO1AA018389 for data collection, analysis, interpretation, and patient recruitment. Suthat Liangpunsakul: U01 grant from the NIAAA and R01 AA025208, U01 AA026917, and 1I01CX000361. Mark R. Thursz: The UK Medical Research Council Stratified Medicine Award (Ref MR/R014019/1), NIHR Imperial Biomedical Research Centre and NIHR Senior Investigator Award (NIHR 200153). |
| Source: |
ISSN: 2471-254X. |
| Publisher Information: |
HAL CCSD; John Wiley & Sons Inc |
| Publication Year: |
2024 |
| Collection: |
Université de Rennes 1: Publications scientifiques (HAL) |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/38727677; PUBMED: 38727677; PUBMEDCENTRAL: PMC11093576 |
| DOI: |
10.1097/hc9.0000000000000431 |
| Availability: |
https://hal.science/hal-04574724; https://hal.science/hal-04574724v1/document; https://hal.science/hal-04574724v1/file/a_polygenic_risk_score_for_alcohol_associated.2.pdf; https://doi.org/10.1097/hc9.0000000000000431 |
| Rights: |
http://creativecommons.org/licenses/by-nc-nd/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.13B228A4 |
| Database: |
BASE |