期刊
METABOLITES
卷 12, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/metabo12060537
关键词
Mendelian randomisation; offspring; birthweight; genetics; maternal; metabolites; glucose; amino acids; lipids; nuclear magnetic resonance
资金
- Wellcome Trust [218495/Z/19/Z]
- University of Bristol Vice-Chancellor's Fellowship
- UK Medical Research Council (MRC) Skills Development Fellowship [MR/P014054/1]
- British Heart Foundation [AA/18/7/34219]
- European Research Council (ERC) under the European Union [101021566]
- British Heart Foundation Chair [CH/F/20/90003]
- US National Institute for Health [R01 DK10324]
- Medical Research Council [MR/P014054/1, MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6]
- University of Bristol
- European Research Council (ERC) [101021566] Funding Source: European Research Council (ERC)
- Wellcome Trust [218495/Z/19/Z] Funding Source: Wellcome Trust
This study investigated the effects of 46 maternal metabolic traits on offspring birthweight using Mendelian randomisation and metabolomics data. The findings suggest that maternal gestational glucose and glutamine are causally related to offspring birthweight.
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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