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The Effect of Pre-Analytical Conditions on Blood Metabolomics in Epidemiological Studies

Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol BS8 2BN, UK
Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, 701 85 Örebro, Sweden
Bristol National Institute of Health Research Biomedical Research Centre, Bristol BS1 3NU, UK
Author to whom correspondence should be addressed.
Metabolites 2019, 9(4), 64;
Received: 11 February 2019 / Revised: 22 March 2019 / Accepted: 27 March 2019 / Published: 3 April 2019
(This article belongs to the Special Issue Metabolomics in Epidemiological Studies)
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Serum and plasma are commonly used in metabolomic-epidemiology studies. Their metabolome is susceptible to differences in pre-analytical conditions and the impact of this is unclear. Participant-matched EDTA-plasma and serum samples were collected from 37 non-fasting volunteers and profiled using a targeted nuclear magnetic resonance (NMR) metabolomics platform (n = 151 traits). Correlations and differences in mean of metabolite concentrations were compared between reference (pre-storage: 4 °C, 1.5 h; post-storage: no buffer addition delay or NMR analysis delay) and four pre-storage blood processing conditions, where samples were incubated at (i) 4 °C, 24 h; (ii) 4 °C, 48 h; (iii) 21 °C, 24 h; and (iv) 21 °C, 48 h, before centrifugation; and two post-storage sample processing conditions in which samples thawed overnight (i) then left for 24 h before addition of sodium buffer followed by immediate NMR analysis; and (ii) addition of sodium buffer, then left for 24 h before NMR profiling. We used multilevel linear regression models and Spearman’s rank correlation coefficients to analyse the data. Most metabolic traits had high rank correlation and minimal differences in mean concentrations between samples subjected to reference and the different conditions tested, that may commonly occur in studies. However, glycolysis metabolites, histidine, acetate and diacylglycerol concentrations may be compromised and this could bias results in association/causal analyses. View Full-Text
Keywords: metabolomics; serum; plasma; nuclear magnetic resonance; pre-analytical phase metabolomics; serum; plasma; nuclear magnetic resonance; pre-analytical phase

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Santos Ferreira, D.L.; Maple, H.J.; Goodwin, M.; Brand, J.S.; Yip, V.; Min, J.L.; Groom, A.; Lawlor, D.A.; Ring, S. The Effect of Pre-Analytical Conditions on Blood Metabolomics in Epidemiological Studies. Metabolites 2019, 9, 64.

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