Human metabolic individuality in biomedical and pharmaceutical research.

Abstract

### Study Hypothesis Although genome-wide association studies have discovered candidate loci for hundreds of human traits, from height to lipid concentrations, the relationships between genetic variants and the phenotypes that they influence often remain unclear. In many cases, the functions of candidate genes are not previously known or discoverable by use of standard techniques. Suhre et al hypothesized that biochemical analysis of serum metabolites can provide an important new resource to determine how some of these risk alleles may promote disease. They leveraged an extensive library of metabolites obtained by profiling human serum from 2 large European cohorts to discover previously unsuspected networks of regulatory genes, metabolites, and diseases. In combination with known human disease associations and biochemical pathways, they extracted novel gene-disease associations that merit testing in follow-up studies. ### How Was the Hypothesis Tested? Metabolites were measured in fasting serum on the Metabolon platform with 2 separate ultra-high-performance liquid chromatography/tandem mass spectrometry injections and 1 gas chromatography/mass spectrometry injection per sample. In the first phase of the analysis, the concentrations of 258 …