| Title: | A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers |
| Journal: | Journal of Hepatology |
| Published: | 14 Oct 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34656649/ |
| DOI: | https://doi.org/10.1016/j.jhep.2021.10.005 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8803006 |
| Citations: | 46 (29 in last 2 years) as of 8 Aug 2024 |
Publication 3877
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Abstract
BACKGROUND & AIMS: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.</p>
METHODS: Three cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC).</p>
RESULTS: A combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption.</p>
CONCLUSIONS: A risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions.</p>
LAY SUMMARY: Excessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.</p>
14 Keywords
- Adult
- Alcohol Drinking
- Case-Control Studies
- Cohort Studies
- Diabetes Mellitus
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Liver Cirrhosis, Alcoholic
- Male
- Middle Aged
- Polymorphism, Single Nucleotide
- Risk Assessment
42 Authors
- John B. Whitfield
- Tae-Hwi Schwantes-An
- Rebecca Darlay
- Guruprasad P. Aithal
- Stephen R. Atkinson
- Ramon Bataller
- Greg Botwin
- Naga P. Chalasani
- Heather J. Cordell
- Ann K. Daly
- Christopher P. Day
- Florian Eyer
- Tatiana Foroud
- Dermot Gleeson
- David Goldman
- Paul S. Haber
- Jean-Marc Jacquet
- 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
- GenomALC Consortium
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