A substantial long-term goal in nutritional genomics is the development of personalized dietary recommendations. In the short term, it is critical to build an understanding of the effect of genetic factors on markers of nutritional health. To gain insight on this problem, we analyzed genetic, dietary and blood metabolite markers of nutritional health from a pediatric cohort. By assessing the genetic data in the context of a metabolic/protein-interaction network, we identified regions of the network containing functionally related genetic loci that were significantly associated with blood metabolites. In particular, molecular subnetworks involved in gastrointestinal and immune function were significantly enriched in these metabolite-associated loci. Further analysis of blood proteins in the same cohort highlighted significant correlations between inflammatory proteins and metabolites central to nutritional health. The implication of these results is that individuals may carry many genetic variants that work together to produce a measurable functional effect on health.



Figure 1 Summary of approach for correlation of genotype and metabolite profile via network analysis. Metabolite data were first summarized by a single principal component and compared to each SNP (gray boxes) in the genetic dataset using generalized estimating equations (GEE). The VEGAS algorithm was then used to determine gene-level p values from SNP-level data. Significant genes were then mapped to the global interaction network to identify regions of significant enrichment.


Figure 2 Genetic association of gastric acid secretion pathway genes with blood metabolites. Rectangles represent pathway genes, and circles represent metabolites. Genes that were significantly correlated with blood metabolites are highlighted in yellow, with three representative example SNPs shown in a–c.



References

Morine, M. J., Monteiro, J. P., Wise, C., Teitel, C., Pence, L., Williams, A., Ning, B., McCabe-Sellers, B., Champagne, C., Turner, J., et al. (2014). Genetic associations with micronutrient levels identified in immune and gastrointestinal networks. Genes & nutrition 9, 408.

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