New biochemical discoveries into developing disease
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 with concentrations of metabolites in the blood. Many of these match variants associated with diseases such as chronic kidney disease, type 2 diabetes and blood clotting.
The team conducted the largest ever study of the human genome for genetic variants associated with metabolites - the biochemical compounds representing the start or end of metabolic reactions - using genome wide association analysis. They were searching 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.
"Our findings provide new insights for many disease-related associations that have been reported in previous studies, including cardiovascular and kidney disorders, type 2 diabetes, cancer, gout, thrombosis and Crohn's disease," says Dr Nicole Soranzo, one of the study's researchers from the Wellcome Trust Sanger Institute. "Often the effects of variants discovered in genome wide association analyses are modest and we perhaps have a poor understanding of the biologic mechanism behind the association. Our approach can overcome these problems and possibly inform individualized therapy/treatment."
In previous studies, scientists have looked at the levels of one or a few metabolic traits; for example, cholesterol levels, or sugar in the blood, that is investigated in the doctor's surgery to help to diagnose disease. The new approach in this work was to assay a much wider range of smaller biochemical compounds, to give as complete a picture as possible of the molecules that are symptoms of disease and those that might contribute to disease.
The hope was that this more complete picture would allow researchers to better understand the function of genetic variants responsible for driving disease. This was the case.
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.
They 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. Dr Christian Gieger adds: "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.
Their study also discovered variants associated with blood clotting and thrombosis.
"We were able to show that variants in or near three genes are associated with a biochemical modification to peptides, a small protein that controls blood clotting. These same variants are variously associated with an increased risk for heart disease, thrombosis and other similar conditions," says Professor Tim Spector, Director of the TwinsUK twin cohort at the Department of Twin Research and Genetic Epidemiology, King's College London, which provided one of the two study samples. "We speculate that this is a new example of a mechanism that alters blood clotting. This discovery could one day lead to improved treatments."
Additionally, the researchers investigated the association of metabolite levels with drug response and treatment, including statins and thalidomide. They showed that in one case, a variant in a gene called ACE, associated with blood pressure control, could undermine treatment effects. The novel biochemical basis could help to identify possible side effects in drug trials and support development of new formulations to reduce side effects.
The 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.
More information: Suhre K, Shin S-Y, Petersen A-K et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature Published online 31 August 2011. doi: 10.1038/Nature10354
Provided by Wellcome Trust Sanger Institute
- Genetic causes identified for disturbances in lipid metabolism Dec 28, 2009 | not rated yet | 0
- Scientists identify 95 genetic variants associated with cholesterol, triglycerides Aug 04, 2010 | not rated yet | 0
- Blood counts are clues to human disease Oct 11, 2009 | not rated yet | 0
- Genes for 9 health indicators Dec 07, 2008 | not rated yet | 0
- Researchers identify gene that regulates glucose levels Jun 03, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Classical and Quantum Mechanics via Lie algebras
Apr 15, 2011 I'd like to open a discussion thread for version 2 of the draft of my book ''Classical and Quantum Mechanics via Lie algebras'', available online at http://lanl.arxiv.org/abs/0810.1019 , and for the...
- More from Physics Forums - Independent Research
More news stories
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
Genetics May 22, 2013 | 4.5 / 5 (4) | 0 |
University of Minnesota Medical School researchers from the Masonic Cancer Center, University of Minnesota, in partnership with the University's Brain Tumor Program, have developed a new mouse model of malignant peripheral ...
Genetics May 20, 2013 | 5 / 5 (1) | 0 |
Northwestern University scientists have shown a gene involved in neurodegenerative disease also plays a critical role in the proper function of the circadian clock.
Genetics May 16, 2013 | 3 / 5 (1) | 1 |
Informed consent is the backbone of patient care. Genetic testing has long required patient consent and patients have had a "right not to know" the results. However, as 21st century medicine now begins to use the tools of ...
Genetics May 16, 2013 | 5 / 5 (1) | 3 |
Ethicists provide framework supporting new recommendations on reporting incidental findings in gene sequencing
In a paper published in Science Express, a group of experts led by bioethicists in the Center for Medical Ethics and Health Policy at Baylor College of Medicine provide a framework for the new American College of Medical Geneti ...
Genetics May 16, 2013 | not rated yet | 0
The World Health Organization voiced deep concern Thursday over the SARS-like virus that has killed 22 people in less than a year, saying it might potentially spread more widely between humans.
59 minutes ago | 5 / 5 (1) | 0
(AP)—Researchers examining the incidence of brain cancer at jet engine manufacturer Pratt & Whitney in Connecticut say they have found no statistically significant elevations in the rate of cancer among workers.
49 minutes ago | not rated yet | 0
(Medical Xpress)—Regulating the distribution of power in neurons is done by a system that makes the national electric grid look simple by comparison. Each neuron has several thousand mitochondria confined ...
13 hours ago | 4.8 / 5 (6) | 0 |
Artemio Martinez balanced his corpulent frame on a stool in a Mexico City street taco stand, downing a sweet soda and eating a final pork-filled corn tortilla.
1 hour ago | not rated yet | 0
The British Menopause Society and Women's Health Concern have today released updated guidelines on Hormone Replacement Therapy (HRT) to provide clarity around the role of HRT, the benefits and the risks. The new guidelines ...
2 hours ago | not rated yet | 0
A brief visual task can predict IQ, according to a new study. This surprisingly simple exercise measures the brain's unconscious ability to filter out visual movement. The study shows that individuals whose ...
19 hours ago | 4.5 / 5 (10) | 1 |