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Sources of variability in metabolite measurements from urinary samples.

ABSTRACT: The application of metabolomics in epidemiological studies would potentially allow researchers to identify biomarkers associated with exposures and diseases. However, within-individual variability of metabolite levels caused by temporal variation of metabolites, together with technical variability introduced by laboratory procedures, may reduce the study power to detect such associations. We assessed the sources of variability of metabolites from urine samples and the implications for designing epidemiologic studies.We measured 539 metabolites in urine samples from the Navy Colon Adenoma Study using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectroscopy (GC-MS). The study collected 2-3 samples per person from 17 male subjects (age 38-70) over 2-10 days. We estimated between-individual, within-individual, and technical variability and calculated expected study power with a specific focus on large case-control and nested case-control studies.Overall technical reliability was high (median intraclass correlation?=?0.92), and for 72% of the metabolites, the majority of total variance can be attributed to between-individual variability. Age, gender and body mass index explained only a small proportion of the total metabolite variability. For a relative risk (comparing upper and lower quartiles of "usual" levels) of 1.5, we estimated that a study with 500, 1,000, and 5,000 individuals could detect 1.0%, 4.5% and 75% of the metabolite associations.The use of metabolomics in urine samples from epidemiological studies would require large sample sizes to detect associations with moderate effect sizes.

SUBMITTER: Xiao Q

PROVIDER: S-EPMC4006796 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Sources of variability in metabolite measurements from urinary samples.

Xiao Qian Q Moore Steven C SC Boca Simina M SM Matthews Charles E CE Rothman Nathaniel N Stolzenberg-Solomon Rachael Z RZ Sinha Rashmi R Cross Amanda J AJ Sampson Joshua N JN

PloS one 20140501 5

<h4>Background</h4>The application of metabolomics in epidemiological studies would potentially allow researchers to identify biomarkers associated with exposures and diseases. However, within-individual variability of metabolite levels caused by temporal variation of metabolites, together with technical variability introduced by laboratory procedures, may reduce the study power to detect such associations. We assessed the sources of variability of metabolites from urine samples and the implicat ...[more]

PMID: 24788433

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Project description:The reproducibility of urinary phthalate metabolite concentrations has not been well characterized in non-pregnant women of reproductive age. Our primary study objectives were to describe the distribution of urinary phthalate metabolites concentrations among a population of Hmong women of reproductive age, and to evaluate intra- and inter-individual variability of phthalate metabolite concentrations. Ten phthalate metabolites were measured in first-morning urine samples collected from 45 women and 20 of their spouses, who were members of the Fox River Environment and Diet Study cohort in Green Bay, Wisconsin. Repeated first-morning urine samples were collected and analyzed from 25 women, who provided up to three samples over approximately 1 month. Measurement variability was assessed using intraclass correlations (ICCs) and surrogate category analysis. Linear mixed models were used to evaluate the associations between participant characteristics and phthalate metabolite concentrations. Nine of the 10 phthalate metabolites were detected in >80% of all analyzed samples, of which seven were detected in all samples. As a measure of reliability, ICCs were strongest for monobenzyl phthalate (0.64) and weakest for the metabolites of di(2-ethylhexyl)phthalate (DEHP) (ranging from 0.13 to 0.22). Similarly, surrogate category analysis suggested that a single urine sample characterized an average 1-month exposure with reasonable accuracy across low, medium and high tertiles for all metabolites, except the DEHP metabolites. Geometric mean concentrations of monoethyl phthalate increased with age, but patterns by education, income, body mass index, environmental tobacco smoke or season were not observed when measures were adjusted for urinary dilution. Our results suggest that the participant characteristics assessed in this study have limited influence on inter-individual variability of phthalate metabolite concentrations. With regard to intra-individual variability, our results suggest that urinary concentrations of some phthalate metabolites are more reproducible over time and are less subjected to exposure misclassification than others (e.g., metabolites of DEHP).

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Sources of variability in metabolite measurements from urinary samples.

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Sources of variability in metabolite measurements from urinary samples.

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