期刊
NUTRIENTS
卷 12, 期 12, 页码 -出版社
MDPI
DOI: 10.3390/nu12123890
关键词
Mendelian randomization; amino acids; tyrosine; type 2 diabetes; GWAS
资金
- Federal Ministry of Science, Germany [01 EA 9401]
- European Union [SOC 95201408 05F02]
- German Cancer Aid [70-2488-Ha I]
- European Community [SOC 98200769 05F02]
- German Ministry of Education and Research (BMBF)
- State of Brandenburg (DZD) [82DZD00302]
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据