Metabolon Blog

Exploring Human Metabolism to Map Genetic Influences

The metabolome describes all the small molecule metabolites in a single organism or biological sample and provides a snapshot of metabolic status at that particular moment. Combining the power of metabolomics with the genetic blueprint created by genome-wide association studies (GWAS) has allowed Metabolon and its collaborators to create an atlas of genetic influences on human blood metabolites.

This atlas will allow researchers to understand more about the impact of genetic polymorphisms on inherited metabolic disorders and metabolically-related genetic disorders, potentially leading to new diagnostics and treatments and new applications for existing drugs.

Metabolomics & Genomics: Making the Links

Metabolomics uses sensitive screening platforms, such as liquid-phase chromatography and gas chromatography-coupled mass spectrometry (LC/MS and GC/MS), to measure all the metabolites present in a biological sample. The resulting metabolic profile can provide a wide variety of information about the system under study, since metabolites change in response to environmental stimuli, lifestyle changes, diseases and drug treatments. 


Metabolomics can also identify changes derived from genetic polymorphisms. In fact, there is a clear link between genomics and metabolomics, because genes code for proteins, many of which have metabolic roles in the cell. As such, the metabolic profile can be seen as a set of surrogate markers of an individual's genotype and phenotype.

Focusing on changes in metabolites based on genetic polymorphisms can help researchers find biomarkers that are important in pharmaceutical drug discovery and development. These biomarkers are also important in diagnostics, as the changes in the metabolic profile caused by the polymorphisms may be detected before symptoms develop.

While genetic testing may just provide a yes or no answer, metabolic profiles yield a fuller picture, potentially giving more detail about prognosis and opening up a route to precision medicine. This could be particularly useful in population screening and patient categorization. 

Integrating metabolomics with other 'omics' technologies, including genomics, transcriptomics and proteomics, can provide in-depth information where the whole is greater than the sum of its parts. This is the rationale behind the creation of the atlas of the genetic influences on human metabolism. 

Creating the Atlas

The atlas was created to help to gain a better understanding of the role of inherited genetic changes in metabolism. These findings could help researchers learn more about metabolic disease and lead to the development of novel treatments. 

A team of researchers from universities, hospitals and pharmaceutical companies combined Metabolon's high-throughput, metabolic profiling platforms and data expertise from a genome-wide association study (GWAS) on thousands of healthy individuals. This project is believed to be the most comprehensive investigation of genetic influences on human metabolism to date.

Using LC/MS and GC/MS, the researchers characterized metabolic profiles from 7,824 European adults from the KORA (Kooperative Gesundheitsforschung in der Region Augsburg) and TwinsUK datasets. The profiles included 529 metabolites, with most representing eight key metabolic pathway groups (amino acids, carbohydrates, cofactors and vitamins, energy, lipids, nucleotides, peptides and xenobiotic metabolism). 

The team then created genetic maps of the areas of the genome that had already been linked with a wide range of metabolic traits. By analyzing around 2.1 million SNPs (single nucleotide polymorphisms; changes of a single nucleotide of the genetic code) and combining genetic and metabolite information using mathematical modelling, the GWAS meta-analysis created a network view of genetic-metabolic interactions and linked 145 SNPs with metabolism, including 90 previously undescribed interactions. 

This is the first comprehensive, high-resolution reference map of human metabolic relationships and their genetic influences. It will help scientists and researchers visualize the important genetic associations between metabolites and SNPs. The atlas is available for online viewing and download, along with extensive biochemical and biological annotations and a database of genetic associations and their biological, medical and pharmacological annotations. 

Key Discoveries & Take-Aways

•The contribution of metabolic loci to variance in metabolite concentrations is high. Understanding the links between genetic loci and metabolite levels will help identify new biomarkers that could expedite clinical trials by helping pharmaceutical R&D scientists select better drug candidates and advance precision medicine.

•The atlas can be used to improve understanding of how complex metabolic systems and pathways and are linked with diseases, potentially identifying new targets for drug and gene therapy.

•The study suggests that blood metabolites might represent the activity of gene products expressed in the brain, as the enzymes associated with the metabolites were widely expressed, potentially allowing researchers to derive more information about patients’ health conditions using less-invasive methods such as blood draws. 

Metabolon: Mapping the Metabolome

Metabolon is a pioneer and leader in metabolomics with more than 15 years’ experience in the field. Our comprehensive technology platform is backed by an extensive chemical reference library and has been used to rapidly identify biomarkers and elucidate biological pathways and processes in both complex and rare diseases. 

Metabolomics unlocks the full potential of genomics data by connecting the dots between the genome and the phenotype. Download our free eBook Bringing the Genome to Life with Metabolomics to learn more.

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