Paper of the year 2007

O The Lancet desta semana atribui o prémio Paper of the year 2007 ao trabalho "Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls" publicado na revista Nature.

"After ranking the papers, more than half of The Lancet‘s editors had the same first choice: The Wellcome Trust Case Control Consortium’s Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.5 Indeed, as soon as this study was published, the fi ndings created repercussions in the medical,6 scientifi c, and popular press. The American Association for the Advancement of Science cited human genetic variation as Science’s breakthrough of the year."

Fica o Abstract como motivação para todos os cientistas e curiosos que visitam este espaço (Nature. 2007 Jun 7;447(7145):661-78).

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls

The Wellcome Trust Case Control Consortium*

There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWAstudy (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined ,2,000 individuals for each of 7 major diseases and a shared set of ,3,000 controls. Case-control comparisons identified 24 independent association signals at P,531027: 1 in bipolar disorder, 1 in coronary artery disease, 9 in Crohn’s disease, 3 in rheumatoid arthritis, 7 in type 1 diabetes and 3 in type 2 diabetes. On the basis of prior findings and replication studies thus-far completed, almost all of these signals reflect genuine susceptibility effects. We observed association at many previously identified loci, and found compelling evidence that some loci confer risk for more than one of the diseases studied. Across all diseases, we identified a large number of further signals (including 58 loci with single-point P values between 1025 and 531027) likely to yield additional susceptibility loci. The importance of appropriately large samples was confirmed by the modest effect sizes observed at most loci identified. This study thus represents a thorough validation of the GWA approach. It has also demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; has generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in the British population is generally modest. Our findings offer new avenues for exploring the pathophysiology of these important disorders. We anticipate that our data, results and software, which will be widely available to other investigators, will provide a powerful resource for human genetics research.