New atlas of molecules paves the way for improved understanding of metabolic diseases

May 11, 2014, Wellcome Trust Sanger Institute

In the most comprehensive exploration of the association between genetic variation and human metabolism, researchers have provided unprecedented 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 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.

Metabolic molecules, known as metabolites, include a wide range of different molecules such as vitamins, lipids, carbohydrates and nucleotides. They make up parts of, or are the products of, all biological pathways. 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 sheer wealth of biological information we have uncovered is extraordinary," says Dr Nicole Soranzo, senior author from the Wellcome Trust Sanger Institute. "It's exciting to think that researchers can now take this freely available information forward to better understand the molecular underpinnings of a vast range of metabolic associations."

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

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 map preferentially to genes that are currently targeted in drug-development programmes. This provides new opportunities to assess genetic influences on , and to assess the potential for existing drugs to treat a wide range of diseases.

"We developed an open-access database that allows researchers to easily search through the findings, to understand genetic variants associated with metabolism one metabolite at a time and in the context of the complete metabolic network," says Dr Gabi Kastenmüller, co-senior author from the Helmholtz Center Munich, Germany. "This database will facilitate drug discovery for and also help researchers to understand the biology behind disease."

Other associations suggest tantalising possibilities for further study. For instance, a number of the identified involved aromatic acids, such as tryptophan, which are important for brain function. 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 , such as antidepressants.

"This work provides an important new window into the underlying human metabolism," said Dr Eric Fauman, study co-author and Associate Research Fellow from Pfizer Inc. "Through targeted Precision Medicine and by linking human disease genes to in vivo biological markers, we hope to enhance our ability to deliver impactful new medicines for patients across a variety of disorders."

Explore further: Genetics meets metabolomics

More information: Shin S-Y et al (2014) An atlas of genetic influences on human blood metabolites. Nature Genetics. DOI: 10.1038/ng.2982

Related Stories

Genetics meets metabolomics

September 1, 2011
Scientists at Helmholtz Zentrum Munich and LMU Munich, in cooperation with Wellcome Trust Sanger Institute and King's College London (KCL), have identified several associations between genetic variants and specific metabolic ...

Statistical test increases power of genetic studies of complex disease

May 7, 2014
The power of genome-wide association studies (GWAS) to detect genetic influences on human disease can be substantially increased using a statistical testing framework reported in the May issue of the journal Genetics.

Genetic regulation of metabolomic biomarkers -- paths to cardiovascular diseases and type 2 diabetes

January 29, 2012
In a study to the genetic variance of human metabolism, researchers have identified thirty one regions of the genome that were associated with levels of circulating metabolites, i.e., small molecules that take part in various ...

New biochemical discoveries into developing disease

August 31, 2011
Researchers have undertaken the most comprehensive investigation of genetic variance in human metabolism and discovered new insights into a range of common diseases. Their work has revealed 37 new variants that are associated ...

Study identifies genetic basis of human metabolic individuality

October 26, 2011
In what is so far the largest investigation of its kind, researchers uncovered a wide range of new insights about common diseases and how they are affected by differences between two persons' genes. The results from this ...

Lifestyle influences metabolism via DNA methylation

September 20, 2013
An unhealthy lifestyle leaves traces in the DNA. These may have specific effects on metabolism, causing organ damage or disease. Scientists of Helmholtz Zentrum München have now identified 28 DNA alterations associated with ...

Recommended for you

Shared genetics may shape treatment options for certain brain disorders

June 20, 2018
Symptoms of schizophrenia and bipolar disorder, including psychosis, depression and manic behavior, have both shared and distinguishing genetic factors, an international consortium led by researchers from Vanderbilt University ...

Simple sugar delays neurodegeneration caused by enzyme deficiency

June 20, 2018
A new therapeutic approach may one day delay neurodegeneration typical of a disease called mucopolysaccharidoses IIIB (MPS IIIB). Neurodegeneration in this condition results from the abnormal accumulation of essential cellular ...

Scientists unravel DNA code behind rare neurologic disease

June 20, 2018
Scientists conducting one of the largest full DNA analyses of a rare disease have identified a gene mutation associated with a perplexing brain condition that blinds and paralyzes patients.

Targeting the engine room of the cancer cell

June 18, 2018
Researchers at Columbia University Irving Medical Center (CUIMC) have developed a highly innovative computational framework that can support personalized cancer treatment by matching individual tumors with the drugs or drug ...

Scientists learn more about how gene linked to autism affects brain

June 18, 2018
New preclinical research shows a gene already linked to a subset of people with autism spectrum disorder is critical to healthy neuronal connections in the developing brain, and its loss can harm those connections to help ...

161 genetic factors for myopia identified

June 15, 2018
The international Consortium for Refractive Error and Myopia (CREAM) recently published the largest-ever genetic study of myopia in Nature Genetics. Researchers from the Gutenberg Health Study at the Medical Center of Johannes ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.