Large study links genes to 7 serious diseases

[Al-khiyal]

LONDON, June 6, 2007: The largest ever study of genes in disease has found 24 genetic risk factors - half of them completely new - linked to seven common conditions, British scientists said Wednesday.

It represents the biggest single haul of disease-associated genes so far, underlining an accelerating pace of discovery that will help researchers unpick the fundamental biology of major illnesses and may lead to more effective drugs.

Last week, researchers found a big batch of breast cancer genes, and two months ago scientists identified a gene that contributes to obesity.

"We are just scratching the surface," said Peter Donnelly of the University of Oxford, who led the Wellcome Trust Case Control Consortium behind the project.

"What will happen over the next couple of years, as these sorts of studies are extended, is that our understanding of the genetics of common diseases will change enormously," he added.

Scientists have known for years that genes, along with environmental factors, play a role in increasing the risk that people will develop problems like heart disease.

But they are still trying to work out which parts of the genome - the 3 billion subunits of DNA in our cells - are actually responsible.

To find out more, Donnelly and colleagues from 50 research groups examined 500,000 genetic markers from each of 17,000 individuals, comparing the genomes of diseased and healthy volunteers.

Their findings, published in the journals Nature and Nature Genetics, included the discovery of four new chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn's disease, the most common form of inflammatory bowel disease.

They also found genetic links to coronary artery disease and hypertension, rheumatoid arthritis, bipolar disorder and type 2 diabetes.

Significantly, many of the genes found were in areas of the genome not previously thought to have been related to the conditions, opening up completely new options for treatment.

Scientists also, for the first time, found a gene linking Crohn's and type 1 diabetes.

The overall increase in risk of disease conferred by the various genetic risk factors was between 1.2 and 1.5 times, suggesting routine testing is not worthwhile.

But Mark Walport, director of the Wellcome Trust medical charity, said there was a clear need for more research in even bigger projects, such as the U.K. Biobank program, which aims to test the DNA of half a million volunteers.

Large study links genes to 7 serious diseases

[Al-khiyal]

7 June 2007 -- A groundbreaking study into the genetic basis of disease has opened the door to new ways of understanding and treating common illnesses affecting millions of people - from manic depression to heart disease.

Scientists have announced the first results of the biggest and most comprehensive investigation into the genes behind seven medical disorders, using a revolutionary approach for analysing vast tracts of the human genome.

The findings have been described as an unprecedented tour de force for British science involving 50 research groups and 200 scientists who pioneered the approach of studying common diseases by analysing the DNA of thousands of people.

The two-year, £9m study took DNA samples from 17,000 people across the UK and built up a database handling 10 billion items of genetic information. It will lead to a new understanding of illnesses as varied as high blood pressure, bipolar disorder and rheumatoid arthritis.

Initial findings from the study released yesterday identified a dozen genes or tiny "point mutations" in the human genome that appear to increase the risk of someone developing a particular disorder during his or her lifetime.

One unexpected result was finding the first genetic link between type 1 diabetes and a bowel condition called Crohn's disease * both were associated with a gene known as PTPN2.

Scientists involved in the study said the research promised to open the way to an era of "personalised" medicine in which doctors routinely analyse the DNA of patients to find out which drugs their genes are best suited for * rather than the existing approach of "one size fits all".

In addition, the methodology of the study could ultimately tease apart the role of nature and nurture in the creation of a person's psyche, making it possible to understand why some people are prone to developing mental illness such as manic depression or schizophrenia.

"Many of the most common diseases are very complex, part of 'nature' and 'nurture', with genes interacting with our environment and lifestyles," said Professor Peter Donnelly of Oxford University, the leader of the scientific consortium behind the study.

"By identifying the genes underlying these conditions, our study should enable scientists to understand better how disease occurs, which people are most at risk and, in time, to produce more effective, more personalised treatments.

"The new approach works well and reliably. Our understanding of the genetics of common diseases will change enormously over the coming years. I think we are just scratching the surface."

The study, published in the journal Nature, came out of the mammoth effort during the 1990s to decode the entire three billion "letters" of the human genome. It was co-ordinated by the Wellcome Trust Case Control Consortium, and funded by the Wellcome Trust, the world's biggest medical research charity.

By analysing the smallest differences in the genetic sequences of patients with a disease and comparing them to the DNA of healthy people, the scientists were able to identify point mutations strongly associated with increasing someone's risk of that illness. The scientists found, for instance, three new genes that each appeared to increase the risk of someone developing Crohn's disease by between 20 and 40 per cent, compared with the risk within the general population.

Thousands of people affected by at least one of the seven diseases gave blood samples that were analysed by sophisticated DNA "chips". These can rifle through huge regions of a person's genome to locate point mutations that are different from the general population.

Mark Walport, director of the Wellcome Trust, said: "Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people.

"What has been achieved in this research is the analysis of half a million genetic variants in each of 17,000 individuals, with the discovery of more than 10 genes that predispose to common diseases."

Britain is in the process of establishing a vast databank of human DNA called UK Biobank * the biggest of its kind in the world * which will store the genes of half a million people who will be closely monitored for the rest of their lives for correlations between genes and disease.

Dr Walport said the findings of the latest study were proof that the UK Biobank approach of analysing DNA on such a large scale will work in terms of finding out why some people fall seriously ill. "This research shows it is possible to analyse human variation in health and disease on an enormous scale," Dr Walport said.

"It shows the importance of studies such as the UK Biobank, which is seeking half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation," he said.

The latest findings come just weeks after scientists used a similar approach to identify four new genes that play a small but significant role in increasing a woman's risk of developing breast cancer, and an earlier discovery of a gene that confers a 70 per cent higher risk of becoming obese.

Professor Donnelly said that it was possible to search for the genetic basis of disease in a fundamentally different way than in the past when the emphasis was on finding the cause of single-gene disorders in families affected by disorders such as cystic fibrosis and Huntington's chorea.

"We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedly herald major advances in how we understand and tackle disease in the future," Professor Donnelly said.

Treatable illnesses...

Bipolar disorder

Also known as manic depression, it affects 100 million people around the world

Coronary heart disease

The most frequent cause of death in Britain, with 100,000 victims every year. By 2020, it will be the biggest killer in the world

Hypertension

High blood pressure affects 16 million people in Britain. Can lead to stroke, heart disease and kidney failure

Rheumatoid arthritis

Nearly 400,000 people in Britain are afflicted with this auto-immune disease of the joints

Type 1 diabetes

Diabetic condition in which sufferers have to inject insulin. Affects 350,000 people in UK

Type 2 diabetes

Almost 2 million Britons are affected by this late-onset disease, which is linked with the growing obesity epidemic

Crohn's disease

Up to 60,000 people are affected by this debilitating bowel condition which can cause distress and pain for a lifetime

The genetic revolution