Find in Library
Search millions of books, articles, and more
Indexed Open Access Databases
Causal effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation studyResearch in context
oleh: 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
Format: | Article |
---|---|
Diterbitkan: | Elsevier 2023-02-01 |
Deskripsi
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.