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Article

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

by
Émilie Gobeil
1,
Ina Maltais-Payette
1,
Nele Taba
2,3,
Francis Brière
4,
Nooshin Ghodsian
1,
Erik Abner
2,
Jérôme Bourgault
1,
Eloi Gagnon
1,
Hasanga D. Manikpurage
1,
Christian Couture
1,
Patricia L. Mitchell
1,
Patrick Mathieu
1,5,
François Julien
1,
Jacques Corbeil
4,6,
Marie-Claude Vohl
7,8,
Sébastien Thériault
1,9,
Tõnu Esko
2,
André Tchernof
1,8 and
Benoit J. Arsenault
1,10,*
1
Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, Québec, QC G1V 4G5, Canada
2
Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, Estonia
3
Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 51010 Tartu, Estonia
4
Centre de Recherche du CHU de Québec, Québec, QC G1V 4G2, Canada
5
Department of Surgery, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
6
Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
7
Centre NUTRISS, Institut sur la Nutrition et les Aliments Fonctionnels, Université Laval, Québec, QC G1V 0A6, Canada
8
School of Nutrition, Université Laval, Québec, QC G1V 0A6, Canada
9
Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
10
Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC G1V 0A6, Canada
*
Author to whom correspondence should be addressed.
Metabolites 2022, 12(5), 440; https://doi.org/10.3390/metabo12050440
Submission received: 23 March 2022 / Revised: 2 May 2022 / Accepted: 11 May 2022 / Published: 13 May 2022
(This article belongs to the Special Issue The Intersection of Metabolomics and Genomics and Their Role in Human Health)
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a complex disease associated with premature mortality. Its diagnosis 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. Our instrument for genetically predicted NAFLD included all independent genetic variants from a recent genome-wide association study. The outcomes included 123 blood metabolites from 24,925 individuals. After correction for multiple testing, a positive effect of NAFLD on plasma tyrosine levels but not on other metabolites was identified. This association was consistent across MR methods and was 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 = 2.19 × 10−5). In a small proof-of-concept study on bariatric surgery patients, blood tyrosine levels were higher in patients with NAFLD than without. This study revealed a potentially causal effect of NAFLD on blood tyrosine levels, suggesting it may represent a new biomarker of NAFLD.
Keywords: non-alcoholic fatty liver disease; tyrosine; biomarker; metabolites; obesity; Mendelian randomization non-alcoholic fatty liver disease; tyrosine; biomarker; metabolites; obesity; Mendelian randomization

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MDPI and ACS Style

Gobeil, É.; Maltais-Payette, I.; Taba, N.; Brière, F.; Ghodsian, N.; Abner, E.; Bourgault, J.; Gagnon, E.; Manikpurage, H.D.; Couture, C.; et al. Mendelian Randomization Analysis Identifies Blood Tyrosine Levels as a Biomarker of Non-Alcoholic Fatty Liver Disease. Metabolites 2022, 12, 440. https://doi.org/10.3390/metabo12050440

AMA Style

Gobeil É, Maltais-Payette I, Taba N, Brière F, Ghodsian N, Abner E, Bourgault J, Gagnon E, Manikpurage HD, Couture C, et al. Mendelian Randomization Analysis Identifies Blood Tyrosine Levels as a Biomarker of Non-Alcoholic Fatty Liver Disease. Metabolites. 2022; 12(5):440. https://doi.org/10.3390/metabo12050440

Chicago/Turabian Style

Gobeil, Émilie, Ina Maltais-Payette, Nele Taba, Francis Brière, Nooshin Ghodsian, Erik Abner, Jérôme Bourgault, Eloi Gagnon, Hasanga D. Manikpurage, Christian Couture, and et al. 2022. "Mendelian Randomization Analysis Identifies Blood Tyrosine Levels as a Biomarker of Non-Alcoholic Fatty Liver Disease" Metabolites 12, no. 5: 440. https://doi.org/10.3390/metabo12050440

APA Style

Gobeil, É., Maltais-Payette, I., Taba, N., Brière, F., Ghodsian, N., Abner, E., Bourgault, J., Gagnon, E., Manikpurage, H. D., Couture, C., Mitchell, P. L., Mathieu, P., Julien, F., Corbeil, J., Vohl, M.-C., Thériault, S., Esko, T., Tchernof, A., & Arsenault, B. J. (2022). Mendelian Randomization Analysis Identifies Blood Tyrosine Levels as a Biomarker of Non-Alcoholic Fatty Liver Disease. Metabolites, 12(5), 440. https://doi.org/10.3390/metabo12050440

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