Suhre, K, et al., Human Metabolic Individuality in Biomedical and Pharmaceutical Research. Nature, 2011. 477(7362): 54-60.
Metabolonresults led to:
Increased understanding of how genetic and environmental factors contribute to complex diseases
Deorphanizationof genes previously of unknown function
A new paradigm for strengthening genomic studies with metabolomics
37 genetic loci associated with blood metabolite concentrations with unprecedented statistical significance
Most of these associations made perfect sense in terms of metabolite and putative gene function
Association between a genetic locus and a metabolite led to identification of a transporter substrate
Genome wide association studies (GWAS) have identified many genetic loci associated with disease, but these associations reveal little about the molecular mechanism that underlies the gene-disease connection. Because genes and environmental factors impinge on metabolism, metabolomicsprovides a powerful tool to understand the molecular events that contribute to complex diseases. Metabolomicsanalysis of two large cohorts identified strong associations between abundance of plasma metabolites and 37 genetic loci, many of clinical interest because of their previously reported connection with a disease. The strong association between SLC16A9and carnitinegenerated the new hypothesis that this gene encoded a carnitinetransporter, and this hypothesis was supported with a simple validation experiment. This study shows that integration of multiple “omics” approaches, with metabolomicsas a vital link between genes/environment and phenotype, provides key insight into the molecular underpinnings of complex disease and reveals new therapeutic strategies.