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Institute of Psychiatry researchers find new genetic clues to causes of schizophrenia

01 July 2009

Results from the largest study of genetics of schizophrenia ever undertaken were published today in the journal Nature and include work by researchers from the Institute of Psychiatry at King’s, as part of a multinational consortium.  The findings expand knowledge of the biology of the disease and provide potential new drug targets.

Schizophrenia, which affects about 1 per cent of adults, tends to run in families. This tripartite study has uncovered a vast array of genetic variation that is estimated to account for about a third of the disease's total heritability.  One of the studies, by the International Schizophrenia Consortium, also found genetic correlations between schizophrenia and bipolar.

The Institute of Psychiatry was part of a team led by deCODE genetics in Iceland.  Funded by the European Commission, the study reveals several new common single-letter variants in the sequence of the human genome (SNPs) linked to risk of the disease.  Researchers analyzed the genomes of more than 50,000 patients and control participants from 14 countries. The work utilised local participants from existing studies such as the Maudsley family Study, the Psychosis twin studies, and the Genetics and Psychosis (GAP) study.

One of the genes identified by the Institute of Psychiatry study, neurogranin (NRGN), appears to play an important role in regulating both memory and cognition, a feature debilitated in schizophrenia. Another gene is the transcription factor 4 (TCF4), involved in brain development.  Some of the polymorphisms most strongly associated with schizophrenia were found in The Major Histocompatibility Complex, a region with genes which regulate the immune response. This lends support to previous research suggesting a possible link between schizophrenia and environmental factors such as infections. It has long been known, for example, that there is a small increase in the number of schizophrenics born in the winter and spring. All of the variants found in this study are very common and each is associated with a modest increase in risk.

'The underlying causes of schizophrenia are poorly understood and this study of schizophrenia genetics was a spectacular success because scientists pooled their resources to create a research project of unprecedented size using advanced ‘gene-chip’ technology to search the genome. This approach paves the way for finding many additional genes associated with the disease and helps identify new biological pathways associated with its development.  These findings have the potential to lead to novel treatments.' said David Collier, Professor of Neuropsychiatric Genetics at the Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London and last author on the paper.

The deCODE genetics study core partners were the National University Hospital Reykjavik, University of Aberdeen, National Publish Health Institute in Helsinki, the Ludwig Maximilians University Munich and the Institute of Psychiatry at King’s College London.  The research team from the Institute of Psychiatry included David Collier, Elvira Bramon, Evangelos Vassos, Ulrich Ettinger, Marco Picchioni,Timi Toulopoulou and Robin Murray. 

A copy of their paper Common variants conferring risk of schizophrenia and the consortium companion papers Common polygenic variation contributes to risk of schizophrenia and bipolar disorder  and Common variants on chromosome 6p22.1 are associated with schizophrenia, can be found here:



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