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

Autor: Bertram Müller-Myhsok, Marie M. Phelan, Juhi K. Gupta, Lu-Yun Lian, Ana Alfirevic, Angharad Care, Laura Goodfellow, Zarko Alfirevic
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Magnetic Resonance Spectroscopy
Microarray
Metabolite
Physiology
Biochemistry
Molecular Bases of Health & Disease
chemistry.chemical_compound
Pregnancy
Risk Factors
biomarker discovery
Genotype
Medicine
Prospective Studies
Biomarker discovery
Research Articles
Oligonucleotide Array Sequence Analysis
integumentary system
mGWAS
Genomics
multiple omics
Phenotype
Cohort
Metabolome
Premature Birth
Gestation
Translational Science
Female
Analysis of variance
Adult
Biophysics
Gestational Age
Polymorphism
Single Nucleotide
Risk Assessment
Predictive Value of Tests
Humans
Metabolomics
SNP
Genetic Predisposition to Disease
Systems Biology & Networks
Lactic Acid
TNF Receptor-Associated Factor 1/genetics
Molecular Biology
business.industry
Premature Birth/blood
Preterm birth
Lactic Acid/blood
Cell Biology
TNF Receptor-Associated Factor 1
NMR
Metabolism
chemistry
Case-Control Studies
Neural Networks
Computer
business
Biomarkers
Biomarkers/blood
Genome-Wide Association Study
Zdroj: BIOSCIENCE REPORTS
Gupta, J, Care, A, Goodfellow, L, Alfirevic, Z, Lian, L-Y, Müller-Myhsok, B, Alfirevic, A & Phelan, MM 2021, ' Metabolic profiling of maternal serum of women at high-risk of spontaneous preterm birth using NMR and MGWAS approach ', Bioscience reports, vol. 41, no. 9, BSR20210759 . https://doi.org/10.1042/BSR20210759
Bioscience Reports
DOI: 10.1042/BSR20210759
Popis: 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.
Databáze: OpenAIRE
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