Using Mendelian Randomisation to Prioritise Candidate Maternal Metabolic Traits Influencing Offspring Birthweight.
Using Mendelian Randomisation to Prioritise Candidate Maternal Metabolic Traits Influencing Offspring Birthweight.
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DOI：
10.3390/metabo12060537
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发表时间：
2022-06-10
期刊：
影响因子：
4.1
通讯作者：
Borges, Maria Carolina
中科院分区：
文献类型：
--
作者：
Barry, Ciarrah-Jane Shannon;Lawlor, Deborah A.;Shapland, Chin Yang;Sanderson, Eleanor;Borges, Maria Carolina
关键词：
怀孕期间显着的生理变化对于支持胎儿生长至关重要；然而，人类研究中关于特定母体代谢特征的作用的证据有限。我们整合孟德尔随机化 (MR) 和代谢组学数据，探讨 46 种母体代谢特征对后代出生体重的影响 (N = 210,267)。我们实施了单变量双样本 MR (UVMR) 来识别影响后代出生体重的候选代谢特征。然后，我们应用两个样本多变量 MR (MVMR) 来联合估计每个候选母亲代谢性状的潜在直接因果效应。在主要分析中，UVMR 表明，较高的母体血糖与较高的后代出生体重相关（每 1 SD 血糖差异，平均出生体重差异为 0.328 SD（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))。在其他分析中，当从独立数据源选择仪器时，UVMR 估计值大致一致，尽管谷氨酰胺和丙氨酸的估计值不精确，并且在使用其他 UVMR 方法时，丙氨酸的估计值有所减弱。 MVMR 结果支持这些代谢物的独立效应，效应估计与 UVMR 结果所见一致。在其余 43 个代谢性状中，UVMR 估计表明大多数脂质相关性状没有影响，而其他氨基酸和酮体则存在高度不确定性。我们的研究结果表明，母亲妊娠期葡萄糖和谷氨酰胺与后代出生体重存在因果关系。
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 (N = 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.
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影响因子：
3.5
作者：
Beaumont RN;Warrington NM;Cavadino A;Tyrrell J;Nodzenski M;Horikoshi M;Geller F;Myhre R;Richmond RC;Paternoster L;Bradfield JP;Kreiner-Møller E;Huikari V;Metrustry S;Lunetta KL;Painter JN;Hottenga JJ;Allard C;Barton SJ;Espinosa A;Marsh JA;Potter C;Zhang G;Ang W;Berry DJ;Bouchard L;Das S;Early Growth Genetics (EGG) Consortium;Hakonarson H;Heikkinen J;Helgeland Ø;Hocher B;Hofman A;Inskip HM;Jones SE;Kogevinas M;Lind PA;Marullo L;Medland SE;Murray A;Murray JC;Njølstad PR;Nohr EA;Reichetzeder C;Ring SM;Ruth KS;Santa-Marina L;Scholtens DM;Sebert S;Sengpiel V;Tuke MA;Vaudel M;Weedon MN;Willemsen G;Wood AR;Yaghootkar H;Muglia LJ;Bartels M;Relton CL;Pennell CE;Chatzi L;Estivill X;Holloway JW;Boomsma DI;Montgomery GW;Murabito JM;Spector TD;Power C;Järvelin MR;Bisgaard H;Grant SFA;Sørensen TIA;Jaddoe VW;Jacobsson B;Melbye M;McCarthy MI;Hattersley AT;Hayes MG;Frayling TM;Hivert MF;Felix JF;Hyppönen E;Lowe WL Jr;Evans DM;Lawlor DA;Feenstra B;Freathy RM
通讯作者：
Freathy RM
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
2.5
作者：
FOWDEN, AL
通讯作者：
FOWDEN, AL
影响因子：
4.6
作者：
Chia, Ai-Ru;de Seymour, Jamie, V;Baker, Philip N.
通讯作者：
Baker, Philip N.