A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry-Reference-Cited by-同舟云学术

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

Published:2024-05-10 Issue:6 Volume:8 Page:
ISSN:2471-254X
Container-title:Hepatology Communications
language:en
Short-container-title:

Author:

Schwantes-An Tae-Hwi¹,Whitfield John B.²,Aithal Guruprasad P.³,Atkinson Stephen R.⁴,Bataller Ramon⁵,Botwin Greg⁶⁷,Chalasani Naga P.⁸,Cordell Heather J.⁹,Daly Ann K.¹⁰,Darlay Rebecca⁹,Day Christopher P.¹¹,Eyer Florian¹²,Foroud Tatiana¹,Gawrieh Samer⁸,Gleeson Dermot¹³,Goldman David¹⁴,Haber Paul S.¹⁵¹⁶,Jacquet Jean-Marc¹⁷,Lammert Craig S.⁸,Liang Tiebing⁸,Liangpunsakul Suthat¹⁸,Masson Steven¹⁰,Mathurin Philippe¹⁹,Moirand Romain²⁰,McQuillin Andrew²¹,Moreno Christophe²²,Morgan Marsha Y.²³,Mueller Sebastian²⁴,Müllhaupt Beat²⁵,Nagy Laura E.²⁶,Nahon Pierre²⁷²⁸²⁹,Nalpas Bertrand¹⁷³⁰,Naveau Sylvie³¹,Perney Pascal³²,Pirmohamed Munir³³,Seitz Helmut K.²⁴,Soyka Michael³⁴,Stickel Felix²⁵,Thompson Andrew³³³⁵,Thursz Mark R.⁴,Trépo Eric²²,Morgan Timothy R.³⁶⁶,Seth Devanshi¹⁵¹⁶³⁷,

Affiliation:

1. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis IN, USA

2. Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Queensland 4029, Australia

3. NIHR Nottingham Biomedical Research Centre, Nottingham University Hospitals and the University of Nottingham, Nottingham NG7 2UH, UK

4. Department of Metabolism, Digestion & Reproduction, Imperial College London, UK

5. Center for Liver Diseases, University of Pittsburgh Medical Center, 3471 Fifth Avenue, Pittsburgh, PA 15213, USA

6. Department of Veterans Affairs, VA Long Beach Healthcare System, 5901 East Seventh Street, Long Beach, CA 90822, USA

7. F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California CA 90048, USA

8. Department of Medicine, Indiana University, Indianapolis, IN 46202-5175, USA

9. Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, International Centre for Life, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK

10. Faculty of Medical Sciences, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

11. Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK

12. Division of Clinical Toxicology, Department of Internal Medicine 2, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany

13. Liver Unit, Sheffield Teaching Hospitals, AO Floor Robert Hadfield Building, Northern General Hospital, Sheffield S5 7AU, UK

14. Office of the Clinical Director and Laboratory of Neurogenetics, NIAAA, Bethesda, MD 20952, USA

15. Edith Collins Centre (Translational Research in Alcohol Drugs and Toxicology), Sydney Local Health District, Missenden Road, Camperdown, NSW 2050, Australia

16. Faculty of Medicine and Health, the University of Sydney, Sydney, NSW 2006, Australia

17. Service Addictologie, CHRU Caremeau, 30029 Nîmes, France

18. Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University and Roudebush Veterans Administration Medical Center, Indianapolis, USA

19. CHRU de Lille, Hôpital Claude Huriez, Rue M. Polonovski CS 70001, 59 037 Lille Cedex, France

20. Univ Rennes, INRA, INSERM, CHU Rennes, Institut NUMECAN (Nutrition Metabolisms and Cancer), F-35000 Rennes, France

21. Molecular Psychiatry Laboratory, Division of Psychiatry, University College London, London WC1E 6DE, UK

22. CUB Hôpital Erasme, Université Libre de Bruxelles, clinique d’Hépatologie, Brussels, Belgium; Laboratory of Experimental Gastroenterology, Université Libre de Bruxelles, Brussels, Belgium

23. UCL Institute for Liver & Digestive Health, Division of Medicine, Royal Free Campus, University College London, London NW3 2PF, UK

24. Department of Internal Medicine, Salem Medical Center and Center for Alcohol Research, University of Heidelberg, Zeppelinstraße 11-33, 69121 Heidelberg, Germany

25. Department of Gastroenterology and Hepatology, University Hospital Zurich, Rämistrasse 100, CH-8901 Zurich, Switzerland

26. Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio, OH 44195, USA

27. Service d'Hépatologie, APHP Hôpital Avicenne et Université Paris 13, Bobigny, France

28. University Paris 13, Bobigny, France

29. Inserm U1162 Génomique fonctionnelle des tumeurs solides, Paris, France

30. DISC, Inserm, 75013 Paris, France

31. Hôpital Antoine-Béclère, 157 Rue de la Porte de Trivaux, 92140 Clamart, France

32. Hôpital Universitaire Caremeau, Place du Pr. Robert Debre, 30029 Nîmes, France

33. MRC Centre for Drug Safety Science, Liverpool Centre for Alcohol Research, University of Liverpool, The Royal Liverpool and Broadgreen University Hospitals NHS Trust, and Liverpool Health Partners, Liverpool, L69 3GL, UK

34. Psychiatric Hospital University of Munich, Nussbaumsstr.7, 80336 Munich, Germany

35. Health Analytics, Lane Clark & Peacock LLP, London, UK

36. Department of Medicine, University of California, Irvine, USA

37. Centenary Institute of Cancer Medicine and Cell Biology, the University of Sydney, Sydney, NSW 2006, Australia

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. 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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Reference34 articles.

1. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations;Khera;Nat Genet,2018

2. Polygenic risk scores: From research tools to clinical instruments;Lewis;Genome Medicine,2020

3. The personal and clinical utility of polygenic risk scores;Torkamani;Nature Reviews Genetics,2018

4. Clinical utility of polygenic risk scores for coronary artery disease;Klarin;Nat Rev Cardiol,2022

5. Towards clinical utility of polygenic risk scores;Lambert;Hum Mol Genet,2019

Cited by 1 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. Alcohol and Hepatocellular Carcinoma;Clinics in Liver Disease;2024-07