Assessment of Analytical Reproducibility of 1H NMR Spectroscopy Based Metabonomics for Large-Scale Epidemiological Research: the INTERMAP Study

摘要

Large-scale population phenotyping for molecular epide- miological studies is subject to all the usual criteria of analytical chemistry. As part of a major phenotyping investigation we have used high-resolution ¹H NMR spectroscopy to characterize 24-h urine specimens ob- tained from population samples in Aito Town, Japan (n) 259), Chicago, IL (n) 315), and Guangxi, China (n 278). We have investigated analytical reproducibility, urine specimen storage procedures, interinstrument vari- ability, and split specimen detection. Our data show that the multivariate analytical reproducibility of the NMR screening platform was >98% and that most classification errors were due to urine specimen handling inhomoge- neity. Differences in metabolite profiles were then as- sessed for Aito Town, Chicago, and Guangxi population samples; novel combinations of biomarkers were detected that separated the population samples. These cross- population differences in urinary metabolites could be related to genetic, dietary, and gut microbial factors.