孟德尔随机化
内科学
2型糖尿病
内分泌学
血糖性
2型糖尿病
医学
全基因组关联研究
胰岛素抵抗
糖尿病
胰岛素
单核苷酸多态性
遗传学
生物
基因型
遗传变异
基因
作者
Yue Sun,Ya‐Ke Lu,Haoyu Gao,Yuxiang Yan
标识
DOI:10.1210/clinem/dgab581
摘要
To assess the causal associations of plasma levels of metabolites with type 2 diabetes mellitus (T2DM) and glycemic traits.Two-sample mendelian randomization (MR) was conducted to assess the causal associations. Genetic variants strongly associated with metabolites at genome-wide significance level (P < 5 × 10-8) were selected from public genome-wide association studies, and single-nucleotide polymorphisms of outcomes were obtained from the Diabetes Genetics Replication and Meta-analysis consortium for T2DM and from the Meta-Analyses of Glucose and Insulin-related Traits Consortium for fasting glucose, insulin, and glycated hemoglobin (HbA1c). The Wald ratio and inverse-variance weighted methods were used for analyses, and MR-Egger was used for sensitivity analysis.The β estimates per 1-SD increase of arachidonic acid (AA) level was 0.16 (95% CI, 0.078-0.242; P < 0.001). Genetic predisposition to higher plasma AA levels were associated with higher fasting glucose levels (β 0.10 [95% CI, 0.064-0.134], P < 0.001), higher HbA1c levels (β 0.04 [95% CI, 0.027-0.061]), and lower fasting insulin levels (β -0.025 [95% CI, -0.047 to -0.002], P = 0.033). Besides, 2-hydroxybutyric acid (2-HBA) might have a positive causal effect on glycemic traits.Our findings suggest that AA and 2-HBA may have causal associations on T2DM and glycemic traits. This is beneficial for clarifying the pathogenesis of T2DM, which would be valuable for early identification and prevention for T2DM.
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