Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.
Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation study.
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母体循环氨基酸对后代出生体重的因果影响：孟德尔随机化研究。
DOI：
10.1016/j.ebiom.2023.104441
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发表时间：
2023-02
期刊：
影响因子：
11.1
通讯作者：
Borges, Maria Carolina
中科院分区：
文献类型：
--
作者：
Zhao, Jian;Stewart, Isobel D.;Baird, Denis;Mason, Dan;Wright, John;Zheng, Jie;Gaunt, Tom R.;Evans, David M.;Freathy, Rachel M.;Langenberg, Claudia;Warrington, Nicole M.;Lawlor, Deborah A.;Borges, Maria Carolina
氨基酸是蛋白质合成、能量代谢、细胞信号传导和基因表达的关键;然而，特定母体氨基酸对胎儿生长的贡献尚不清楚。我们采用两样本孟德尔随机化（MR）和血清氨基酸水平全基因组关联研究（GWAS）的汇总数据，以出生体重为代表，探讨母体循环氨基酸对胎儿生长的影响（样本1，n = 86，507）和英国生物库和早期生长遗传学联盟中后代出生体重的母体GWAS，调整胎儿基因型效应（样品2，n = 406，063，具有母体和/或胎儿基因型效应估计）。共有106个独立的单核苷酸多态性与19个氨基酸（p < 4.9 × 10−10）密切相关，被用作遗传工具变量（IV）。MR主成分分析采用Wald比法和方差倒数加权法。进行了一系列敏感性分析，以探讨IV假设违反。我们的研究结果提供了证据表明，母体循环谷氨酰胺（母体氨基酸水平每增加一个标准差，后代出生体重增加59 g，95% CI：7，110）和丝氨酸（27 g，95% CI：9，46）增加，而亮氨酸（-59 g，95% CI：-106，-11）和苯丙氨酸（-25 g，95% CI：-47，-4）降低后代出生体重。这些发现得到了敏感性分析的支持。我们的研究结果加强了怀孕期间母体循环氨基酸在健康胎儿生长中的关键作用的证据。对本研究做出贡献的资助机构的完整列表可以在致谢中找到。
Amino acids are key to protein synthesis, energy metabolism, cell signaling and gene expression; however, the contribution of specific maternal amino acids to fetal growth is unclear. We explored the effect of maternal circulating amino acids on fetal growth, proxied by birthweight, using two-sample Mendelian randomisation (MR) and summary data from a genome-wide association study (GWAS) of serum amino acids levels (sample 1, n = 86,507) and a maternal GWAS of offspring birthweight in UK Biobank and Early Growth Genetics Consortium, adjusting for fetal genotype effects (sample 2, n = 406,063 with maternal and/or fetal genotype effect estimates). A total of 106 independent single nucleotide polymorphisms robustly associated with 19 amino acids (p < 4.9 × 10−10) were used as genetic instrumental variables (IV). Wald ratio and inverse variance weighted methods were used in MR main analysis. A series of sensitivity analyses were performed to explore IV assumption violations. Our results provide evidence that maternal circulating glutamine (59 g offspring birthweight increase per standard deviation increase in maternal amino acid level, 95% CI: 7, 110) and serine (27 g, 95% CI: 9, 46) raise, while leucine (−59 g, 95% CI: −106, −11) and phenylalanine (−25 g, 95% CI: −47, −4) lower offspring birthweight. These findings are supported by sensitivity analyses. Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth. A full list of funding bodies that contributed to this study can be found under Acknowledgments.
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影响因子：
2
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan N;Thompson J
通讯作者：
Thompson J
影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
DOI：
10.2741/s162
发表时间：
2011-01-01
期刊：
Frontiers in bioscience (Scholar edition)
影响因子：
--
作者：
Brown LD;Green AS;Limesand SW;Rozance PJ
通讯作者：
Rozance PJ
影响因子：
4.4
作者：
Huang X;Anderle P;Hostettler L;Baumann MU;Surbek DV;Ontsouka EC;Albrecht C
通讯作者：
Albrecht C
影响因子：
7.1
作者：
Huxley, Rachel;Owen, Christopher G.;Collins, Rory
通讯作者：
Collins, Rory