Genetic and Environmental Contributions to Variation in the Stable Urinary NMR Metabolome over Time: A Classic Twin Study

Genes, sex, age,
diet, lifestyle, gut microbiome, and multiple
other factors affect human metabolomic profiles. Understanding metabolomic
variation is critical in human nutrition research as metabolites that
are sensitive to change versus those that are more stable might be
more informative for a particular study design. This study aims to
identify stable metabolomic regions and determine the genetic and
environmental contributions to stability. Using a classic twin design, 1H nuclear magnetic resonance (NMR) urinary metabolomic profiles
were measured in 128 twins at baseline, 1 month, and 2 months. Multivariate
mixed models identified stable urinary metabolites with intraclass
correlation coefficients ≥0.51. Longitudinal twin modeling
measured the contribution of genetic and environmental influences
to variation in the stable urinary NMR metabolome, comprising stable
metabolites. The conservation of an individual’s stable urinary
NMR metabolome over time was assessed by calculating conservation
indices. In this study, 20% of the urinary NMR metabolome is stable
over 2 months (intraclass correlation (ICC) 0.51–0.65). Common
genetic and shared environmental factors contributed to variance in
the stable urinary NMR metabolome over time. Using the stable metabolome,
91% of individuals had good metabolomic conservation indices ≥0.70.
To conclude, this research identifies 20% of the urinary NMR metabolome
as stable, improves our knowledge of the sources of metabolomic variation
over time, and demonstrates the conservation of an individual’s
urinary NMR metabolome.