The largest ever study of the genetics behind seven of the world’s most common yet complex diseases is being hailed as a new dawn in medical research.
The £9 million Wellcome Trust Case Control Consortium (WTCCC) is one of the UK's largest and most successful academic collaborations to date. It has examined DNA samples from 17,000 people across the UK, bringing together 50 leading research groups and 200 scientists in the field of human genetics. Over two years, they have analysed a staggering 10 billion pieces of genetic information, looking at the genetic variations that underlie seven common diseases – bipolar disorder, coronary artery disease, Crohn’s disease, hypertension, rheumatoid arthritis, and types 1 and 2 diabetes – and the results have been published in the journals Nature and Nature Genetics.
Gene linking type 1 diabetes and Crohn’s disease
Among the most significant new findings in the study are four chromosome regions containing genes that can predispose to type 1 diabetes and three new genes for Crohn's disease. Importantly, for the first time, the researchers have found a gene linking these two autoimmune diseases, known as PTPN2.
The study has also confirmed the importance of autophagy in the development of Crohn's disease. Autophagy, or 'self-eating', is responsible for clearing unwanted material, such as bacteria, from within cells and this may be key to the interaction of gut bacteria in health and in inflammatory bowel disease, and could have clinical significance in the future, say the researchers.
Research from the WTCCC has already played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes, published in April in advance of the main study, and it has also found a major gene region on chromosome 9, identified by independent studies on coronary heart disease.
Peter Donnelly, chair of the WTCCC, said that “many of the most common diseases are very complex, part 'nature' and 'nurture', with genes interacting with our environment and lifestyles," so 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." His enthusiasm was echoed by Mark Walport, director of the Wellcome Trust, which funded the study, who noted that "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."
He noted that “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 ten genes that predispose to common diseases.” Dr Walport added that the research reveals “ that it is possible to analyse human variation in health and disease on an enormous scale” and shows the importance of studies such as UK Biobank, which is looking for half a million volunteers aged between 40 and 69, with the aim of understanding the links between health, the environment and genetic variation.
"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," concluded Prof Donnelly. "This approach will undoubtedly herald major advances in how we understand and tackle disease in the future."
The WTCCC also noted that further analysis will look at tuberculosis, breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis and the results are expected later this year.
