Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics

Tuulia Tynkkynen, Qin Wang, Jussi Ekholm, Olga Anufrieva, Pauli Ohukainen, Jouko Vepsäläinen, Minna Männikkö, Sirkka Keinänen-Kiukaanniemi, Michael V Holmes, Matthew Goodwin, Susan Ring, John C Chambers, Jaspal Kooner, Marjo-Riitta Järvelin, Johannes Kettunen, Michael Hill, George Davey Smith, Mika Ala-Korpela

Research output: Contribution to journalArticle (Academic Journal)peer-review

9 Citations (Scopus)
336 Downloads (Pure)


Background: Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high-throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available.
Methods: We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative lineshape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1,004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n=995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n=578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n= 4,548).
Results: Intra-assay metabolite variations were mostly <5% indicating high robustness and accuracy of the urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance.
Conclusions: Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided.
Original languageEnglish
Pages (from-to)978-993
Number of pages16
JournalInternational Journal of Epidemiology
Issue number3
Early online date25 Jan 2019
Publication statusPublished - 1 Jun 2019


  • genome-wide analyses
  • Metabolomics
  • multicentre
  • open access
  • serum
  • urine

Fingerprint Dive into the research topics of 'Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics'. Together they form a unique fingerprint.

Cite this