MRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK.
MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
Nat Commun. 2019 Mar 5;10(1):1060. doi: 10.1038/s41467-019-08936-1.
Circulating levels of glycine have previously been associated with lower incidence of coronary heart disease (CHD) and type 2 diabetes (T2D) but it remains uncertain if glycine plays an aetiological role. We present a meta-analysis of genome-wide association studies for glycine in 80,003 participants and investigate the causality and potential mechanisms of the association between glycine and cardio-metabolic diseases using genetic approaches. We identify 27 genetic loci, of which 22 have not previously been reported for glycine. We show that glycine is genetically associated with lower CHD risk and find that this may be partly driven by blood pressure. Evidence for a genetic association of glycine with T2D is weaker, but we find a strong inverse genetic effect of hyperinsulinaemia on glycine. Our findings strengthen evidence for a protective effect of glycine on CHD and show that the glycine-T2D association may be driven by a glycine-lowering effect of insulin resistance.
先前的研究表明，循环甘氨酸水平与冠心病（CHD）和 2 型糖尿病（T2D）的发病率降低有关，但甘氨酸是否发挥病因作用仍不确定。我们对 80003 名参与者的甘氨酸全基因组关联研究进行了荟萃分析，并利用遗传方法研究了甘氨酸与心血管代谢疾病之间的因果关系和潜在机制。我们确定了 27 个遗传位点，其中 22 个以前没有报道过与甘氨酸有关。我们表明，甘氨酸与较低的 CHD 风险存在遗传相关性，并且发现这可能部分是由血压驱动的。甘氨酸与 T2D 的遗传相关性证据较弱，但我们发现高胰岛素血症对甘氨酸有很强的负向遗传效应。我们的研究结果进一步证实了甘氨酸对 CHD 的保护作用，并表明甘氨酸与 T2D 的关联可能是由胰岛素抵抗导致甘氨酸降低所驱动的。
