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Article

Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes

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Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany
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German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany
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Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
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Leibniz Institute for Prevention Research and Epidemiology-BIPS, 28359 Bremen, Germany
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Human Genomics Research Group, Department of Biomedicine, University of Basel, 4031 Basel, Switzerland
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Institute of Human Genetics, Division of Genomics, Life & Brain Research Centre, University Hospital of Bonn, 53105 Bonn, Germany
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Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany
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Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85354 Freising-Weihenstephan, Germany
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Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore
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Molecular Epidemiology Research Group, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC), 13125 Berlin, Germany
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Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health (BIH), 10117 Berlin, Germany
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MDC/BIH Biobank, Max Delbrueck Center for Molecular Medicine in the Helmholtz Association (MDC) and Berlin Institute of Health (BIH), 13125 Berlin, Germany
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Institute of Nutritional Science, University of Potsdam, 14558 Nuthetal, Germany
*
Author to whom correspondence should be addressed.
Nutrients 2020, 12(12), 3890; https://doi.org/10.3390/nu12123890
Received: 24 November 2020 / Revised: 14 December 2020 / Accepted: 16 December 2020 / Published: 19 December 2020
(This article belongs to the Special Issue Amino Acid Nutrition and Metabolism Related to Health and Well Being)
Circulating levels of branched-chain amino acids, glycine, or aromatic amino acids have been associated with risk of type 2 diabetes. However, whether those associations reflect causal relationships or are rather driven by early processes of disease development is unclear. We selected diabetes-related amino acid ratios based on metabolic network structures and investigated causal effects of these ratios and single amino acids on the risk of type 2 diabetes in two-sample Mendelian randomization studies. Selection of genetic instruments for amino acid traits relied on genome-wide association studies in a representative sub-cohort (up to 2265 participants) of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study and public data from genome-wide association studies on single amino acids. For the selected instruments, outcome associations were drawn from the DIAGRAM (DIAbetes Genetics Replication And Meta-analysis, 74,124 cases and 824,006 controls) consortium. Mendelian randomization results indicate an inverse association for a per standard deviation increase in ln-transformed tyrosine/methionine ratio with type 2 diabetes (OR = 0.87 (0.81–0.93)). Multivariable Mendelian randomization revealed inverse association for higher log10-transformed tyrosine levels with type 2 diabetes (OR = 0.19 (0.04–0.88)), independent of other amino acids. Tyrosine might be a causal trait for type 2 diabetes independent of other diabetes-associated amino acids. View Full-Text
Keywords: Mendelian randomization; amino acids; tyrosine; type 2 diabetes; GWAS Mendelian randomization; amino acids; tyrosine; type 2 diabetes; GWAS
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MDPI and ACS Style

Jäger, S.; Cuadrat, R.; Wittenbecher, C.; Floegel, A.; Hoffmann, P.; Prehn, C.; Adamski, J.; Pischon, T.; Schulze, M.B. Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes. Nutrients 2020, 12, 3890. https://doi.org/10.3390/nu12123890

AMA Style

Jäger S, Cuadrat R, Wittenbecher C, Floegel A, Hoffmann P, Prehn C, Adamski J, Pischon T, Schulze MB. Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes. Nutrients. 2020; 12(12):3890. https://doi.org/10.3390/nu12123890

Chicago/Turabian Style

Jäger, Susanne, Rafael Cuadrat, Clemens Wittenbecher, Anna Floegel, Per Hoffmann, Cornelia Prehn, Jerzy Adamski, Tobias Pischon, and Matthias B. Schulze. 2020. "Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes" Nutrients 12, no. 12: 3890. https://doi.org/10.3390/nu12123890

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