New complex gene atlas to help battle human diseases

Researchers have provided insights into how genetic variants influence complex disease and drug response through metabolic pathways.

The team 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.

The team measured the levels of a large number of metabolites, both those already known and many as yet uncharacterised, from many different metabolic pathways.

They found 90 new genetic associations, trebling the figure of known genetic associations with metabolites. In many of the cases where metabolites were known, the team 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 programmes. 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.

Dr Eric Fauman, study co-author and Associate Research Fellow from Pfizer Inc said this work provides an important new window into the genetic variation underlying human metabolism.

He said through targeted Precision Medicine and by linking human disease genes to in vivo biological markers, they are hope to enhance their ability to deliver impactful new medicines for patients across a variety of disorders.