586Effects of maternal circulating amino acids on offspring birthweight: a Mendelian randomisation analysis. (2nd September 2021)

• Record Type: Journal Article
• Authors: Zhao, Jian; Freathy, Rachel; Evans, David; Warrington, Nicole; Langenberg, Claudia; Stewart, Isobel; Lotta, Luca; Pietzner, Maik; Borges, Maria Carolina; Lawlor, Deborah
• Is Part Of: International journal of epidemiology. Volume 50(2021)Supplement 1
• Publication Date: 2021-09-02
• Subjects: Epidemiology -- Periodicals; 614.4
• DOI: 10.1093/ije/dyab168.757
• Languages: English
• ISSNs: 0300-5771

Abstract

Abstract: Background: It is suggested amino acids are critical for fetal growth, but analyses assessing causality are lacking. Mendelian randomisation (MR) can be used to examine causal effects under instrumental variable (IV) assumptions. Methods: We conducted a two-sample MR study utilizing summary data from genome-wide association studies (GWAS) of amino acids (sample 1, n = 86, 507) and of offspring birthweight (sample 2, combined UK Biobank and Early Growth Genetics Consortium, n = 406, 063). Seventy-five independent single nucleotide polymorphisms (SNPs) robustly associated with 18 amino acids (p < 4.9 × 10 -10 ) were used as genetic instruments. Wald ratio and inverse variance weighted methods were used in MR main analysis. Sensitivity analyses were performed to explore IV assumption violations. To explore whether there was consistency between SNP-amino acid associations in pregnancy and in the GWAS, the latter were compared to associations in the Born in Bradford cohort. Results: There was evidence of positive causal effects of maternal alanine (51.9 g birthweight increase per SD increase in amino acid level, 95% CI: 24.2, 79.5), glutamine (51.3 g, 95% CI: 33.5, 69.0), glycine (10.4 g, 95% CI: 1.3, 19.6) and serine (27.1 g, 95% CI: 11.2, 43.0) on birthweight and inverse causal effects of maternal isoleucine (-109.7 g, 95% CI: -194.6, -24.9) and histidine (-41.1 g, 95% CI: -78.5, -3.7) on birthweight. Sensitivity analyses to explore reverse causality and bias due to horizontal pleiotropy supported our findings. Conclusions: Some maternal circulating amino acids have causal effects on birthweight. Key messages: MR can be extended to probe effects of maternal nutrition on offspring development.