Common disease genes identified
19 February 2008
The past couple of decades have seen enormous efforts made to identify genes increasing our susceptibility to common diseases. Whole-genome scans now enable the entire genome to be screened for possible contributory factors. Unfortunately, the field has been blighted by ‘false positives’ - statistical associations discovered in one population but not apparent in another. Now, though, an approach spearheaded by the Wellcome Trust Case Control Consortium is finally generating robust data.
The Consortium is making use of the dense map of genetic markers produced by the SNP Consortium and its follow-up, the International HapMap Project. Advances in technology have enabled high-throughput analysis of hundreds of thousands of such markers in large numbers of individuals.
The Consortium also depended on coordination among the UK’s leading researchers (and groups abroad). Crucially, genetic associations identified in one population could be tested in other, increasing confidence that an association is real.
In essence, case-control approaches look for genetic variations that are more common in people with a given condition than in matched healthy individuals. The Consortium used the approach on a variety of conditions. This work, and follow-up by individual disease groups and collaborators, has now identified more than 30 genetic factors contributing to diseases including heart disease, type 1 and type 2 diabetes, Crohn’s disease, rheumatoid arthritis and ankylosing spondylitis. The number continues to increase with more detailed analysis and follow-up of the data.
Interestingly, the approach also led to the identification of genes associated with other characteristics, such as weight and height.
Because so many factors affect common diseases, and a single gene will generally have only a small effect, the identification of susceptibility genes will have limited value in the prediction of disease in individuals. Far more important is the insight provided into mechanisms of disease, opening up new avenues of research into causes and possible treatments.
Further reading
- Wellcome Trust Case Control Consortium. Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature 2007;447(7145):661-78.
- Weedon MN et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat Genet 2007;39(10):1245-50.
- Samani NJ et al. Genomewide association analysis of coronary artery disease. N Engl J Med 2007;357(5):443-53.
- Parkes M et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nat Genet 2007;39(7):830-2.
- Zeggini E et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007;316(5829):1336-41.
- Frayling TM et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. 2007;316(5826):889-94.
- Todd JA et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet 2007;39(7):857-64.