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Mendelian Randomization Analysis Identifies Blood Tyrosine Levels as a Biomarker of Non-Alcoholic Fatty Liver Disease

Authors :
Erik Abner
Nele Taba
Éloi Gagnon
André Tchernof
Jacques Corbeil
Marie-Claude Vohl
Émilie Gobeil
Ina Maltais-Payette
François Julien
Patrick Mathieu
Hasanga D. Manikpurage
Christian Couture
Francis Briere
Tõnu Esko
Jérôme Bourgault
Benoit J. Arsenault
Nooshin Ghodsian
Patricia L. Mitchell
Sébastien Thériault
Source :
Metabolites; Volume 12; Issue 5; Pages: 440
Publication Year :
2022
Publisher :
Multidisciplinary Digital Publishing Institute, 2022.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a complex cardiometabolic disease associated with premature mortality. The diagnosis of NAFLD is challenging and the identification of biomarkers causally influenced by NAFLD may be clinically useful. We aimed at identifying blood metabolites causally impacted by NAFLD using two-sample Mendelian randomization (MR) with validation in a population-based biobank and a cohort of patients undergoing bariatric surgery. Our instrument for genetically-predicted NAFLD (the study exposure) included all independent genetic variants (n=7 SNPs) from a recent genome-wide association study on NAFLD. The study outcomes included 123 blood lipids, lipoproteins and metabolites measured in 24,925 individuals from 10 European cohorts. After correction for multiple testing, we identified a positive effect of NAFLD on plasma tyrosine levels but not on other metabolites. The association between NAFLD and tyrosine levels was consistent across MR methods and robust to outliers and pleiotropy. In observational analyses performed in the Estonian Biobank (10,809 individuals including 359 patients with NAFLD), after multivariable adjustment, tyrosine levels were positively associated with the presence of NAFLD (odds ratio per 1-SD increment = 1.23 (95% confidence interval = 1.12-1.36, p = 2.19e-05). In a sample of 138 patients undergoing bariatric surgery, compared to patients without NAFLD, blood tyrosine levels were higher in those with NAFLD, but were comparable among patients with or without non-alcoholic steatohepatitis. This analysis revealed a potentially causal effect of NAFLD on blood tyrosine levels, suggesting that blood tyrosine levels may represent a new biomarker of NAFLD.Graphical abstract

Details

Language :
English
ISSN :
22181989
Database :
OpenAIRE
Journal :
Metabolites; Volume 12; Issue 5; Pages: 440
Accession number :
edsair.doi.dedup.....6a0cdb3e1c5d8fb09688514e0527f403
Full Text :
https://doi.org/10.3390/metabo12050440