The research has revealed eleven new genetic regions associated with the blood levels of the metabolites, including new loci affecting well-established risk markers for cardiovascular disease and potential biomarkers for type 2 diabetes.
In a study to the genetic variance of human metabolism, specialists have identified thirty one regions of the genome that were related with levels of circulating metabolites, i.e., small molecules that take part in different chemical reactions of human body. Many of the studied metabolites are biomarkers for cardiovascular disease or related disorders, accordingly the loci uncovered may provide valuable insight into the biological processes leading to common diseases.
Lab tests used in the clinic typically monitor one or few circulating metabolites. The researchers used a high throughput method called nuclear magnetic resonance that can measure more than hundred different metabolites in one assay. This provides a considerably more in-depth picture of circulating metabolic compounds.
The group assayed 117 detailed metabolic markers, including amino acids, lipids and lipoprotein subclasses, and conducted the largest genome-wide association analysis of this type, in terms of study sample size of 8330 individuals and 7.7 million genomic markers studied. They revealed, in total, 31 genetic regions related with the blood levels of the metabolites.
Among the discoveries were two new loci influencing serum cholesterol subclass measures, well-established risk markers for cardiovascular disease, and five new loci affecting levels of amino acids recently discovered to be potential biomarkers for type 2 diabetes. The found variants have significant effects on the metabolite levels, the effect sizes being in general considerably larger than the known common variants for complex disease have.
Additionally, using twin pair samples, the scientists indicated that the metabolite levels show a high degree of heritability. This result suggests that the studied metabolites are describing better the underlying biology than the routinely used lab tests. In this way, the examination provides further support for the use of detailed data on multitude of metabolites in genetic studies to provide novel biological insights and to help in elucidating the processes leading to common diseases.