In a comprehensive exploration of the association between genetic variation and human metabolism, researchers have provided new insights into how genetic variants influence complex disease and drug response through metabolic pathways. A team from the Wellcome Trust Sanger Institute has linked 145 genetic regions with more than 400 molecules involved in human metabolism in human blood. This atlas of genetic associations with metabolism provides many new opportunities to understand the molecular pathways underlying associations with common complex diseases. This new compendium of associations between genetic regions and metabolite levels provides a powerful tool to identify genes that could be used in drug and diagnostic tests for a wide range of metabolic disorders.
The team measured the levels of a large number of metabolites, both those already known and many as yet uncharacterized, from many different metabolic pathways. Researchers found 90 new genetic associations, tripling the figure of known genetic associations with metabolites. In many of the cases where metabolites were known, they were able to link the molecule to gene function. They mapped genes to their likely substrates or products and linked these to a number of conditions, including hypertension, cardiovascular disease, and diabetes. They further found that these genetic regions map preferentially to genes that are currently targeted in drug-development programs. This provides new opportunities to assess genetic influences on drug response, and to assess the potential for existing drugs to treat a wide range of diseases.
While this study did not measure association of metabolites in the brain, these genetic findings open new avenues to assess potential genetic influences on brain function and responses to drugs that affect brain function, such as antidepressants. The study appears in Nature Genetics; read the article preview.
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