GWAS Reveals Genetic Variance in Metabolism

By Bio-IT World Staff

September 6, 2011 | A study published last week in Nature establishes a strong association between biochemical levels and the genetics of an individual. Researchers looked at genetic variation in human metabolism and discovered 37 new variants associated with concentrations of metabolites in the blood. The Genome Wide Association Study (GWAS) was carried out by researchers at Helmholtz Zentrum Munchen Institute in Munich, Germany, the Wellcome Trust Sanger Institute, King’s College and Metabolon.   

Researchers collected serum from 2,820 individuals, and were looking for genetic influences on levels of more than 250 compounds in people's blood, including lipids, sugars, vitamins, amino acids and many others. They discovered variants that have a significant effect on the levels of these compounds, and hence on the underlying biological and disease processes.

“This is by far the most comprehensive GWAS to investigate the association of biochemical levels in blood with human genetics,” said John Ryals, president and CEO of Metabolon in a press release. “The associations uncovered in this work provide new functional insights for many disease-related associations that have been reported in previous studies, including cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, venous thromboembolism, and Crohn’s disease.”  

The researchers identified 37 genetic loci associated with blood metabolite concentrations, of which 25 exhibit effect sizes that are unusually high for GWAS, accounting for 10-60% of metabolite levels per allele copy. Further, 23 of these loci describe new genetic associations with metabolic traits and 14 replicate and extend our knowledge of known associations.  

Among the discoveries made by the team was a previously unknown association of mannose, a natural sugar, with diabetes-associated variants; this link suggests a new line of research to examine the role of mannose in diabetes, both as a diagnostic and as part of the disease process. hey also identified a possible mechanism to detoxify substances, which could affect the risk of developing kidney disease. This followed the discovery of a highly significant association with the NAT8 gene.

"These are remarkable findings powered by our method that enables researchers to identify new and potentially relevant metabolic processes and pathways," says Professor Karsten Suhre in a press release. Dr Christian Gieger added: "To improve effectively treatment through biomedicine, we need to put genetics into its biological context. In trying to do this in our study, we have identified new molecules of interest that could be clinically significant." Both are the lead authors from the Helmholtz Center Munich, German Research Centre for Environmental Health.

The Wellcome Trust reports that data will be made publicly available as a knowledge-based resource on the internet to aid future studies, and biological, as well as clinical, interpretation of genome wide association studies. The paper can be found at http://www.nature.com/nature/journal/v477/n7362/full/nature10354.html.