“The paper outlines how we identified a version of the Neuregulin 1 gene that confers an approximately twofold higher than average risk of developing schizophrenia.”

This is one of the most compelling studies to link the variations in a specific gene to a susceptibility to schizophrenia. The finding is particularly interesting because so little is currently understood about the causes of this disease. This study and subsequent work in mice have given us a firm foothold in what we believe is one of the basic biological perturbations underlying schizophrenia, and a promising starting point for the development of new drugs to treat it.

  Does it describe a new discovery or new methodology that's useful to others?

The correlation we have made between Neuregulin 1 and schizophrenia was a breakthrough, all the more important because other groups had previously presented evidence that suggested a possible link between schizophrenia and the region on chromosome 8 in which the gene encoding Neuregulin 1 lies. Our ability to conduct population- and genome-wide linkage studies with large cohorts and high-resolution marker sets no doubt contributed to our ability to home in efficiently on the gene itself. The publication of our findings has enabled other groups to conduct replication studies of the link between Neuregulin and schizophrenia in a number of other cohorts around the world.

The paper outlines how we identified a version of the Neuregulin 1 gene that confers an approximately twofold higher than average risk of developing schizophrenia. We did this through the analysis of genome-wide genotypic data and detailed phenotypic information from more than 800 volunteer patients and unaffected family members from across Iceland. By looking at this data in the context of our genealogical database of the entire Icelandic population, we identified a region on chromosome 8 that was shared by patients to a much higher degree than would be expected by chance. We then looked at a much denser set of genetic markers spread across this region, and found that a version of the gene encoding Neuregulin 1 was found in twice as many patients as controls. Our functional studies in mice offer compelling additional evidence for the involvement of the Neuregulin 1 pathway in some of the major biological dysfunctions in schizophrenia. Our analysis of mice in which certain segments of the Neuregulin 1 gene or of the gene encoding one of its key receptors, ErbB4, were knocked out, showed that the knockout mice exhibited behaviors and disruptions in normal neurotransmission similar to those seen in schizophrenics. The findings discussed in this paper are the foundation for our drug discovery work aimed at finding a better treatment for this disease.

  How did you become involved in this research?

We are conducting gene discovery work in 50 of the most common diseases and are applying our findings to develop better drugs. Schizophrenia, although it affects only some one percent of the population, is as such a common disease and one for which new treatments based on the biology of the disease are dearly needed. It was one of our earlier gene discovery projects and one which we are very pleased to see yield exciting results.