Mendelian randomization study on amino acid metabolism suggests tyrosine as causal trait for type 2 diabetes
| Autor: | Jerzy Adamski, Susanne Jäger, Anna Floegel, Rafael R. C. Cuadrat, Matthias B. Schulze, Per Hoffmann, Clemens Wittenbecher, Cornelia Prehn, Tobias Pischon |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male 0301 basic medicine Glycine 030209 endocrinology & metabolism Genome-wide association study lcsh:TX341-641 Type 2 diabetes Biology GWAS Mendelian randomization Tyrosine Amino acids Article Amino Acids Aromatic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Aromatic amino acids Humans Genetic Predisposition to Disease Prospective Studies Genetic association chemistry.chemical_classification Genetics amino acids Nutrition and Dietetics Methionine Amino Acids Gwas Mendelian Randomization Type 2 Diabetes Mendelian Randomization Analysis Middle Aged medicine.disease Amino acid 030104 developmental biology Diabetes Mellitus Type 2 chemistry Cardiovascular and Metabolic Diseases Case-Control Studies Female type 2 diabetes lcsh:Nutrition. Foods and food supply Amino Acids Branched-Chain tyrosine Genome-Wide Association Study Food Science |
| Zdroj: | Nutrients 12:3890 (2020) Nutrients, Vol 12, Iss 3890, p 3890 (2020) Nutrients Volume 12 Issue 12 Nutrients, 12(12):3890 |
| Popis: | 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&ndash 0.93)). Multivariable Mendelian randomization revealed inverse association for higher log10-transformed tyrosine levels with type 2 diabetes (OR = 0.19 (0.04&ndash 0.88)), independent of other amino acids. Tyrosine might be a causal trait for type 2 diabetes independent of other diabetes-associated amino acids. |
| Databáze: | OpenAIRE |
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