Large Genome Study Finds Genes Behind Common Diseases

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Main Category: Genetics
Also Included In: Crohn's / IBD;  Diabetes
Article Date: 07 Jun 2007 - 0:00 PST

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In the largest ever study published to date, a consortium of UK scientists has discovered over 20 genes and regions of the human genome that contribute to diseases such as diabetes, rheumatoid arthritis and coronary heart disease.

The Wellcome Trust Control Consortium's 9 million pound study is a collaboration of 200 UK scientists from 50 teams at dozens of UK institutions. Between them they have analysed nearly 10 billion pieces of genetic information from 17,000 people throughout the UK in two years.

Their work comprises the largest ever study on the genetic origins of disease and is published this week in the journals Nature and Nature Genetics.

The human genome is made up of a long sequence of more than 3 million base pairs of four DNA building blocks with the chemical names adenine (A), thymine (T), guanine (G) and cytosine (C). Every now and again there occurs a disruption to the order of a group of the building blocks, a mutation, and these are called single nucleotide polymorphisms (SNPs, pronounced "snips" for short).

People who share the same ethnic lineage often share the same SNPs. For instance, most Europeans share about 8 million of them. In this study, the scientists examined half a million SNPs and found more than 10 genes plus fragments of DNA that appear to be linked to elevated risk of some common diseases.

Chair of the Consortium, Professor Peter Donnelly from the University of Oxford said that:

"Many of the most common diseases are very complex, part 'nature' and 'nurture', with genes interacting with our environment and lifestyles."

"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," he added.

Many of the discoveries were a surprise; scientists had not thought them to be related to disease. As more large scale studies complete their work, it is likely that more such surprises could be waiting to be discovered.

Dr Mark Walport, Director of the Wellcome Trust explained:

"This research shows that it is possible to analyse human variation in health and disease on an enormous scale. 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."

Of particular significance is the discovery of a link between the autoimmune diseases type 1 diabetes and Crohn's disease which causes inflammatory bowel. A gene called PTPN2 appears to link the two conditions.

Also, in the case of Crohn's, the study has confirmed the importance of the role of autophagy in the development of the disease. Autophagy (literally self- eating) is a cellular process for clearing cells of rubbish like unwanted bacteria. In Crohn's disease the immune system reacts to normal gut bacteria, and more understanding of autophagy and how it deals with bacteria could have clinical significance.

Professor John Todd from the University of Cambridge, who led this part of the study said:

"The link between type 1 diabetes and Crohn's disease is one of the most exciting findings to come out of the Consortium."

"It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn's disease are increasingly well understood and we hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future," he added.

The Consortium scientists analysed DNA samples from 2,000 patients for each of seven major diseases (bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes) and 3,000 healthy controls. The next stage will be to get samples from larger populations to confirm the results.

Professor Donnelly summed up the contribution this study has made:

"Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works."

"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," he concluded.

However, the researchers are cautious when it comes to suggesting how soon genetic screening could be used to help individuals find out if whether they are going to develop a disease.

Having a predisposition is no longer seen as a matter of a particular gene. It could be a complex pattern of several genes acting together, and a tipping point that is decided by environment and lifestyle factors. However, the knowledge of whether they have one or both genes that predisposes an illness could help people make informed decisions about lifestyle and reduce the risk of that condition being triggered.

The Consortium is also looking into the genes behind tuberculosis (TB), breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis and will be publishing their findings later this year.

UK Biobank is a registered charity and major UK medical research project that aims to improve the prevention, diagnosis and treatment of a wide range of serious and life-threatening illnesses. These illnesses include cancer, heart diseases, diabetes, arthritis and forms of dementia.

The project is currently recruiting 500,000 people aged 40 to 69 from across the UK to be assessed and give blood samples.

The UK Biobank is funded by the Wellcome Trust, the Medical Research Council, the Department of Health, the Scottish Executive and the Northwest Regional Development Agency. It is also backed by the National Health Service and many of the UK's major medical research charities, including the British Heart Foundation and Cancer Research UK.

Click here for Nature.

Click here for Nature Genetics.

Click here for UK Biobank.

Written by: Catharine Paddock
Writer: Medical News Today
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

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