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

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-relat...

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Autores principales: Jäger, Susanne, Cuadrat, Rafael, Wittenbecher, Clemens, Floegel, Anna, Hoffmann, Per, Prehn, Cornelia, Adamski, Jerzy, Pischon, Tobias, Schulze, Matthias B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766372/
https://www.ncbi.nlm.nih.gov/pubmed/33352682
http://dx.doi.org/10.3390/nu12123890
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author Jäger, Susanne
Cuadrat, Rafael
Wittenbecher, Clemens
Floegel, Anna
Hoffmann, Per
Prehn, Cornelia
Adamski, Jerzy
Pischon, Tobias
Schulze, Matthias B.
author_facet Jäger, Susanne
Cuadrat, Rafael
Wittenbecher, Clemens
Floegel, Anna
Hoffmann, Per
Prehn, Cornelia
Adamski, Jerzy
Pischon, Tobias
Schulze, Matthias B.
author_sort Jäger, Susanne
collection PubMed
description 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.
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spelling pubmed-77663722020-12-28 Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes Jäger, Susanne Cuadrat, Rafael Wittenbecher, Clemens Floegel, Anna Hoffmann, Per Prehn, Cornelia Adamski, Jerzy Pischon, Tobias Schulze, Matthias B. Nutrients Article 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. MDPI 2020-12-19 /pmc/articles/PMC7766372/ /pubmed/33352682 http://dx.doi.org/10.3390/nu12123890 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jäger, Susanne
Cuadrat, Rafael
Wittenbecher, Clemens
Floegel, Anna
Hoffmann, Per
Prehn, Cornelia
Adamski, Jerzy
Pischon, Tobias
Schulze, Matthias B.
Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title_full Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title_fullStr Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title_full_unstemmed Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title_short Mendelian Randomization Study on Amino Acid Metabolism Suggests Tyrosine as Causal Trait for Type 2 Diabetes
title_sort mendelian randomization study on amino acid metabolism suggests tyrosine as causal trait for type 2 diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766372/
https://www.ncbi.nlm.nih.gov/pubmed/33352682
http://dx.doi.org/10.3390/nu12123890
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