Metabolic profiling of maternal serum of women a high-risk of spontaneous preterm birth using NMR and MGWAS approach



Gupta, Juhi K ORCID: 0000-0002-8292-9846, Care, Angharad ORCID: 0000-0003-2131-0406, Goodfellow, Laura ORCID: 0000-0002-8111-5007, Alfirevic, Zarko, Lian, Lu-Yun, Mueller-Myhsok, Bertram ORCID: 0000-0002-0719-101X, Alfirevic, Ana ORCID: 0000-0002-2801-9817 and Phelan, Marie M
(2021) Metabolic profiling of maternal serum of women a high-risk of spontaneous preterm birth using NMR and MGWAS approach. BIOSCIENCE REPORTS, 41 (9). BSR20210759-.

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Abstract

Preterm birth (PTB) is a leading global cause of infant mortality. Risk factors include genetics, lifestyle choices and infection. Understanding the mechanism of PTB could aid the development of novel approaches to prevent PTB. This study aimed to investigate the metabolic biomarkers of PTB in early pregnancy and the association of significant metabolites with participant genotypes. Maternal sera collected at 16 and 20 weeks of gestation, from women who previously experienced PTB (high-risk) and women who did not (low-risk controls), were analysed using 1H nuclear magnetic resonance (NMR) metabolomics and genome-wide screening microarray. ANOVA and probabilistic neural network (PNN) modelling were performed on the spectral bins. Metabolomics genome-wide association (MGWAS) of the spectral bins and genotype data from the same participants was applied to determine potential metabolite-gene pathways. Phenylalanine, acetate and lactate metabolite differences between PTB cases and controls were obtained by ANOVA and PNN showed strong prediction at week 20 (AUC = 0.89). MGWAS identified several metabolite bins with strong genetic associations. Cis-eQTL analysis highlighted TRAF1 (involved in the inflammatory pathway) local to a non-coding SNP associated with lactate at week 20 of gestation. MGWAS of a well-defined cohort of participants highlighted a lactate-TRAF1 relationship that could potentially contribute to PTB.

Item Type: Article
Uncontrolled Keywords: Humans, Premature Birth, Genetic Predisposition to Disease, Lactic Acid, TNF Receptor-Associated Factor 1, Oligonucleotide Array Sequence Analysis, Magnetic Resonance Spectroscopy, Risk Assessment, Risk Factors, Case-Control Studies, Prospective Studies, Predictive Value of Tests, Gestational Age, Pregnancy, Phenotype, Polymorphism, Single Nucleotide, Adult, Female, Genome-Wide Association Study, Metabolomics, Metabolome, Biomarkers, Neural Networks, Computer
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 08 Oct 2021 09:24
Last Modified: 18 Jan 2023 21:27
DOI: 10.1042/BSR20210759
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3139715