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Mendelian randomization study on amino acid metabolism suggests tyrosine as causal trait for type 2 diabetes

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Item Type:Article
Title:Mendelian randomization study on amino acid metabolism suggests tyrosine as causal trait for type 2 diabetes
Creators Name:Jäger, S. and Cuadrat, R. and Wittenbecher, C. and Floegel, A. and Hoffmann, P. and Prehn, C. and Adamski, J. and Pischon, T. and Schulze, M.B.
Abstract: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 log(10)-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.
Keywords:Mendelian Randomization, Amino Acids, Tyrosine, Type 2 Diabetes, GWAS
Page Range:3890
Date:19 December 2020
Official Publication:https://doi.org/10.3390/nu12123890
PubMed:View item in PubMed

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