EBioMedicine (Feb 2023)

Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation studyResearch in context

  • Jian Zhao,
  • Isobel D. Stewart,
  • Denis Baird,
  • Dan Mason,
  • John Wright,
  • Jie Zheng,
  • Tom R. Gaunt,
  • David M. Evans,
  • Rachel M. Freathy,
  • Claudia Langenberg,
  • Nicole M. Warrington,
  • Deborah A. Lawlor,
  • Maria Carolina Borges

Journal volume & issue
Vol. 88
p. 104441

Abstract

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Summary: Background: 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. Methods: 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. Findings: 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. Interpretation: Our findings strengthen evidence for key roles of maternal circulating amino acids during pregnancy in healthy fetal growth. Funding: A full list of funding bodies that contributed to this study can be found under Acknowledgments.

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