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Mendelian randomization study on amino acid metabolism suggests tyrosine as causal trait for type 2 diabetes.
Nutrients 12:3890 (2020)
Postprint
Forschungsdaten
DOI
PMC
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Amino Acids ; Gwas ; Mendelian Randomization ; Type 2 Diabetes ; Tyrosine; Genome-wide Association; Genetic-variants; Insulin-resistance; Risk; Metaanalysis; Imputation; Loci
ISSN (print) / ISBN
2072-6643
e-ISSN
2072-6643
Zeitschrift
Nutrients
Quellenangaben
Band: 12,
Heft: 12,
Artikelnummer: 3890
Verlag
MDPI
Verlagsort
Basel
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Molekulare Endokrinologie und Metabolismus (MEM)
Förderungen
State of Brandenburg (DZD)
German Ministry of Education and Research (BMBF)
German Cancer Aid
Federal Ministry of Science, Germany
German Ministry of Education and Research (BMBF) and the State of Brandenburg
European Community
European Union
German Ministry of Education and Research (BMBF)
German Cancer Aid
Federal Ministry of Science, Germany
German Ministry of Education and Research (BMBF) and the State of Brandenburg
European Community
European Union