deCODE's population approach

From target discovery through the clinical development of new drugs, deCODE's work is powered by our population approach to human genetics. deCODE is the world leader in gene discovery in the common diseases, and has isolated major genetic factors involved in eleven of the biggest public health challenges from cardiovascular disease to cancer. These genes have provided us with drug targets rooted in the basic biology of human disease, enabling us to pursue drug discovery and development work on a small number of targets with high potential therapeutic impact. We are also applying our population approach to make the clinical development process a more effective means of testing new drugs and maximizing their potential benefit to patients.

deCODE's advantage arises from the complexity of the challenge. The common diseases, such as heart attack, asthma, stroke and cancer, result from the interplay of multiple genes and environmental and health factors. Moreover, our understanding of the biological mechanisms involved in most of these diseases is limited. Genetics offers a means of unraveling this complexity, but to do so requires the ability to gather and correlate detailed information on disease and genetic variation across as large a group of people as possible: a population. To do this efficiently it is also critical to have accurate and comprehensive genealogical records, the only means for tracing how the genetic components of disease travel between generations.


A family tree of 102 Icelandic asthma patients linked together over eleven generations back to a founder couple born in the mid-17th century.

A population with all three sets of data - genetic, medical and genealogical - is the scarce resource in human genetics. In Iceland, deCODE has brought this information together. Along with its genealogy database covering the entire present day population and stretching back to the founding of the country more than 1000 years ago, deCODE has gathered genotypic and medical data from more than 100,000 volunteer participants in our gene research in Iceland - over half of the adult population. Using its unique genealogy database, deCODE clusters patients affected by any disease into large extended families. Applying its high-throughput genotyping capabilities and proprietary datamining instruments, deCODE first "maps" genes through linkage analysis, homing in on small segments of particular chromosomes that large numbers of related patients share to a much higher degree than would be expected by chance. More detailed analysis of these regions with denser sets of markers enables us to isolate the key genes conferring risk of the disease as well as the versions or haplotypes that are highly correlated with the disease.

deCODE's approach thus allows for a virtually hypothesis-free discovery process that pinpoints the key inherited causes of disease. And it does so in the biological system that matters most - in people. Following the isolation of major genes, we analyze the proteins the genes encode, the biological function of these proteins, and the interaction of these with other proteins to flesh out the biological pathway of a given disease. In most cases, the proteins encoded by the disease-genes themselves offer excellent drug targets. If they do not, other points in the disease pathway may be selected for therapeutic intervention. Our program in DG041 offers an example of how our approach has taken us in only three years from the identification of a disease gene and novel target and into mide stage human clinical trials. At the same time, as we have shown in our drug development program in heart attack, there are existing compounds developed by others for different indications that we may be able to in-license and enter directly into clinical trials, thereby leapfrogging over several years of discovery work.

In our clinical development work we are pioneering the application of population data to the drug development process, creating what we call the Information-rich Clinical TrialTM. The goal of the IRCTTM paradigm is to bring detailed genetic and phenotypic data to bear on the design, recruitment, and results analysis of the clinical development process, making trials much more sensitive instruments for gauging the effectiveness of new drugs. Because we can recruit cohorts with a detailed understanding of the pathways through which patients are susceptible to disease, the IRCT approach enables trials that are smaller, faster and more informative than traditional trials. We believe this offers an important means of better managing risk in the drug development process and of maximizing the therapeutic potential of new drugs.

Participation and Privacy Protection
Over ninety percent of people invited to take part in deCODE's research in Iceland do so. All genetic material and medical information used in our research are obtained in accordance with the most rigorous international standards for patient consent. We also utilize one of the few third-party identity encryption systems in use in medical research today. This system ensures that all information on individuals - genealogical, medical and genetic - employed in our research is anonymized, identifiable only by an encrypted ID code generated by the Icelandic government's Data Protection Authority.