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

Authors
  • Gupta, Juhi K.1, 2
  • Care, Angharad2
  • Goodfellow, Laura2
  • Alfirevic, Zarko2
  • Lian, Lu-Yun3
  • Müller-Myhsok, Bertram1, 4
  • Alfirevic, Ana1, 2
  • Phelan, Marie M.3
  • 1 verpool, Liverpool, L69 3GL, UK
  • 2 Harris-Wellbeing Research Centre, University Department, Liverpool Women’s Hospital, Liverpool, L8 7SS, UK
  • 3 NMR Centre for Structural Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, L69 7ZB, UK
  • 4 Max Planck Institute of Psychiatry, Munich 80804, Germany
Type
Published Article
Journal
Bioscience Reports
Publisher
Portland Press
Publication Date
Aug 31, 2021
Volume
41
Issue
9
Identifiers
DOI: 10.1042/BSR20210759
PMID: 34402867
PMCID: PMC8415214
Source
PubMed Central
Keywords
Disciplines
  • Research Articles
License
Unknown

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.

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