Assessment of analytical reproducibility of 1H NMR spectroscopy based metabonomics for large-scale epidemiological research: the INTERMAP Study.
Large-scale population phenotyping for molecular epidemiological 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 obtained 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 variability, 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 inhomogeneity. Differences in metabolite profiles were then assessed 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.
Biological Chemistry, Biomedical Sciences Division, Imperial College London, Sir Alexander Fleming Building, South Kensington, London UK. m.dumas@imperial.ac.uk
Marc-Emmanuel
ME
Dumas
Elaine C
EC
Maibaum
Claire
C
Teague
Hirotsugu
H
Ueshima
Beifan
B
Zhou
John C
JC
Lindon
Jeremy K
JK
Nicholson
Jeremiah
J
Stamler
Paul
P
Elliott
Queenie
Q
Chan
Elaine
E
Holmes
D015415:Biomarkers / Q000652:urine; D002681:China; D002947:Cities; D003430:Cross-Sectional Studies; D005819:Genetic Markers / Q000235:genetics / Q000502:physiology; D006801:Humans; D007564:Japan; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards; D015999:Multivariate Analysis; D010641:Phenotype; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013048:Specimen Handling / Q000379:methods* / Q000592:standards; D013997:Time Factors; D014481:United States; D016482:Urinalysis
D015415:Biomarkers; D005819:Genetic Markers