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Background & Aims: Only a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.
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).
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.
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.
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.
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http://dx.doi.org/10.1016/j.jhep.2021.10.005 | DOI Listing |
J Anim Sci
December 2024
TERRA Teaching and Research Center, University of Liège, Gembloux Agro-Bio Tech (ULiège-GxABT), 5030 Gembloux, Belgium.
Using genetic selection for raising intact boars, which improves growth and feed efficiency, is a promising alternative to castration for mitigating boar taint. Selective breeding has the potential to help to identify and select for genetic lines with a reduced risk of boar taint. Common phenotypes are laboratory measurements of skatole (SKA) and androstenone (ANON) i.
View Article and Find Full Text PDFEur J Pediatr
December 2024
Department of Pathology, Children's Hospital of Nanjing Medical University, Nanjing, 210008, Jiangsu, China.
Unlabelled: Neuroblastoma, " a malignancy originating from neural crest cells, is most commonly diagnosed in children and adolescents. Polymorphisms within the long noncoding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) are believed to have the capacity to alter an individual's susceptibility to various cancers. This study aimed to investigate the link between HOTTIP gene polymorphisms and neuroblastoma susceptibility.
View Article and Find Full Text PDFEur J Nutr
December 2024
Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, 07747, Jena, Germany.
Background: Excessive intake of fatty acids is a key factor contributing to metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effects of saturated fatty acids (SFA) and unsaturated fatty acids (UFA) on the development of MASLD are uncertain. Therefore, we conducted two-sample Mendelian randomization studies and animal experiments to explore the effects of SFA, monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on the risk of developing MASLD.
View Article and Find Full Text PDFCurr Microbiol
December 2024
School of Bio Science and Technology, VIT University, Vellore, Tamil Nadu, 632014, India.
Pseudomonas aeruginosa is a prevalent nosocomial pathogen and a significant reservoir of antimicrobial resistance genes in residential and built environments. It is also widespread in various indoor and outdoor settings, including sewage, surface waters, soil, recreational waters (both treated and untreated), and industrial effluents. Surveillance efforts for P.
View Article and Find Full Text PDFArch Dermatol Res
December 2024
Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, Shannxi, China.
Lipid metabolism disorders are frequently noted in atopic dermatitis (AD) patients, prompting the long-term use of lipid-lowering drugs. However, the causal effects of circulating lipids and different lipid-lowering drugs on the risk of AD are not thoroughly understood. Using publicly available genome-wide association studies (GWAS) summary data from two different cohorts, a series of Mendelian randomization (MR) analyses were conducted to explore the causal effects of genetically proxied circulating lipids and lipid-lowering drugs on the risk of AD.
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