'Genome-wide association' throws up new genetic markers - but drug development remains some way off
A multi-centre genome scanning project that has analysed half a million genetic markers in thousands of healthy people and people with a range of common diseases (including diabetes and hypertension) has revealed previously unknown genetic variants of the diseases. It is likely to be some time, however, before these findings are translated into new therapies.
The Wellcome Trust Case Control Consortium, comprising more than 50 research teams, used gene chip technology to analyse 500 000 genetic markers in 2000 cases each of seven common diseases: 14 000 individuals in total. These findings were compared with data with 3000 healthy control patients.
The study revealed 24 genetic variants - many of which had been previously unknown - associated with the diseases, which included types 1 and 2 diabetes, coronary heart disease, rheumatoid arthritis and hypertension.
’For many common diseases we know that there are genetic components but we do not know what they are,’ Peter Donnelly, chairman of the consortium, told Chemistry World. ’People have tried a number of approaches to find the relevant genetic markers but with only sporadic success. Our approach was to use genome-wide association and we have demonstrated that this is a reliable new method for studying the genetics of common diseases. We have been able to do this because of microarray technology which enabled us to look at half a million genetic locations affordably, plus the fact that we have extensive collections of DNA from patients and we have sequenced the human genome.’
Donnelly added, ’This is just the tip of a wave. Over the next couple of years there will be enormous advances in our understanding of common diseases.’
But it is likely to be some time before new therapies emerge from such findings. Andy Merritt of the pharmaceutical company GlaxoSmithKline said, ’This approach is exciting and has a lot of potential, but there is a lot of work between now and the development of small-molecule targeted drugs.’
Research will need to be done to pinpoint precisely which genes are involved in the diseases; the specific proteins that the genes encode; and how these operate within a given biochemical pathway.
’What is interesting about this genome-wide approach is that it might identify genes that we would not have necessarily thought to look at in relation to a particular disease,’ Merritt said. ’Furthermore, we know that there can be a lot of genetic variability within a given class of disease and this type of analysis should ultimately help us match our therapies more closely with a given individual’s disease type.’
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The Wellcome Trust Case Control Consortium, Nature, 2007, 447, 661