Barry Ciarrah-Jane Shannon, Lawlor Deborah A, Shapland Chin Yang, Sanderson Eleanor, Borges Maria Carolina
MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 2BN, UK.
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK.
Metabolites. 2022 Jun 10;12(6):537. doi: 10.3390/metabo12060537.
Marked physiological changes in pregnancy are essential to support foetal growth; however, evidence on the role of specific maternal metabolic traits from human studies is limited. We integrated Mendelian randomisation (MR) and metabolomics data to probe the effect of 46 maternal metabolic traits on offspring birthweight ( = 210,267). We implemented univariable two-sample MR (UVMR) to identify candidate metabolic traits affecting offspring birthweight. We then applied two-sample multivariable MR (MVMR) to jointly estimate the potential direct causal effect for each candidate maternal metabolic trait. In the main analyses, UVMR indicated that higher maternal glucose was related to higher offspring birthweight (0.328 SD difference in mean birthweight per 1 SD difference in glucose (95% CI: 0.104, 0.414)), as were maternal glutamine (0.089 (95% CI: 0.033, 0.144)) and alanine (0.137 (95% CI: 0.036, 0.239)). In additional analyses, UVMR estimates were broadly consistent when selecting instruments from an independent data source, albeit imprecise for glutamine and alanine, and were attenuated for alanine when using other UVMR methods. MVMR results supported independent effects of these metabolites, with effect estimates consistent with those seen with the UVMR results. Among the remaining 43 metabolic traits, UVMR estimates indicated a null effect for most lipid-related traits and a high degree of uncertainty for other amino acids and ketone bodies. Our findings suggest that maternal gestational glucose and glutamine are causally related to offspring birthweight.
孕期显著的生理变化对于支持胎儿生长至关重要；然而，来自人类研究的关于特定母体代谢特征作用的证据有限。我们整合了孟德尔随机化（MR）和代谢组学数据，以探究46种母体代谢特征对后代出生体重（n = 210,267）的影响。我们实施单变量双样本MR（UVMR）来识别影响后代出生体重的候选代谢特征。然后应用双样本多变量MR（MVMR）来联合估计每个候选母体代谢特征的潜在直接因果效应。在主要分析中，UVMR表明母体葡萄糖水平较高与后代出生体重较高相关（葡萄糖每增加1个标准差，平均出生体重差异为0.328个标准差（95%CI：0.104，0.414）），母体谷氨酰胺（0.089（95%CI：0.033，0.144））和丙氨酸（0.137（95%CI：0.036，0.239））也如此。在额外分析中，从独立数据源选择工具变量时，UVMR估计结果大致一致，尽管谷氨酰胺和丙氨酸的结果不精确，并且使用其他UVMR方法时丙氨酸的估计值有所衰减。MVMR结果支持这些代谢物的独立效应，效应估计与UVMR结果一致。在其余43种代谢特征中，UVMR估计表明大多数脂质相关特征无效应，其他氨基酸和酮体的不确定性较高。我们的研究结果表明，母体孕期葡萄糖和谷氨酰胺与后代出生体重存在因果关系。
