Genetic vulnerability to schizophrenia can be explained by the combined effect of a large number of common genes, according to a new study published in the prominent journal Nature. These genes are also linked to bipolar disorder.
"As well as the connection between schizophrenia and the combined effect of a large number of genes, we have also obtained some indications that individual genes which form part of the immune system may provide protection against schizophrenia," says Christina Hultman, Professor of psychiatric epidemiology at Karolinska Institutet. "This is something that we will now be investigating more closely."
The newly-published study is the result of collaboration between a large number of researchers across Europe and the US, through the International Schizophrenia Consortium. Over the last three years, the research group at Karolinska Institutet has contacted almost 3,500 people with schizophrenia and 3,500 people who do not have the illness. The study in question includes 560 of these Swedish patients and 400 Swedish control cases, as well as approximately 6,000 more patients and control cases from Bulgaria, the UK, Portugal and Ireland.
The researchers have found that schizophrenia - which occurs in just under 1% of the population - seems to be the result of a large number of genes, each of which has a small effect. These genes are thought to explain a third of the overall genetic vulnerability, and are largely shared with bipolar disorder. However, there is no connection with non-psychiatric diseases such as cardiovascular disease, rheumatism and diabetes. In a study published in The Lancet earlier this year, the same group of researchers demonstrated that the risk of developing bipolar disorder is increased if someone in the family has schizophrenia, and vice versa.
A new strategy used by the researchers in the study involved investigating the combined effect of a large number of genetic variants which together represent half of the common genetic variants in the gene pool. Each genetic variant was assigned a risk score based on how its incidence differs between the group with schizophrenia and the control group. These ratings were then added up for all variants, and a combined overall rating was calculated for each participant in the study.
In order to verify the results, the participants were divided up into two groups: one in which the risk rating was derived, and one in which it was applied. In order to rule out the increased risk of schizophrenia being due to other factors, the groups were divided up in a number of different ways, according to factors such as gender and nationality.
"Regardless of the way in which the groups were divided up, we can see that the cumulative risk rating is related to schizophrenia," adds Professor Hultman. "Computer simulations were then carried out to estimate the proportion of the genetic vulnerability contributed by these combined variants."
Christina M. Hultman, Paul Lichtenstein and other researchers from the International Schizophrenia Consortium"Common polygenic variation contributes to risk of schizophrenia that overlaps with bipolar disorder"
Nature, online publication 1 juli 2009, DOI: 10.1038/nature08185.