The study, which is published in the scientific journal Nature Genetics, is based on blood samples from more than 59 000 individuals and provides the hitherto strongest clues to what causes schizophrenia.
Blood samples from 11 200 people in Sweden, 5000 with schizophrenia and 6 200 healthy controls, have been analyzed together with blood samples from additional 48 000 patients and controls worldwide. By investigating common DNA changes, so called single nucleotide polymorphisms (SNPs), the researchers could identify the risk genes.
“We found 22 risk variants which were more common in individuals with schizophrenia, thirteen are new discoveries and one region has been linked to bipolar disorder previously”, says study co-author Anna Kähler, researcher at the Department of Medical Epidemiology and Biostatistics.
Ten million SNPs per study participant were examined, which enabled the researchers to find the risk variants that were more common in individuals with schizophrenia compared to controls. This gives scientists an unprecedented opportunity to understand the nature of the genetic changes that increase the risk for schizophrenia and suggests new biological hypotheses to investigate further.
“The results show that genetic variation in the form of common SNPs, unlike rare mutations, constitutes a significant risk factor for schizophrenia”, says Karolinska Institutet Professor Christina Hultman, leader of the study and the last author together with Patrick Sullivan at the University of North Carolina (UNC). “Thousands of SNPs are estimated to be involved, which in turn affects a smaller number of genes important for biological and biochemical reaction chains.”
One of the two pathways identified by the study is a calcium channel pathway. This pathway includes the genes CACNA1C and CACNB2, whose proteins touch each other as part of an important process in nerve cells. The other is the ‘micro-RNA 137’ pathway. This pathway includes its namesake gene, MIR137 – which is a known regulator of neuronal development – and at least a dozen other genes regulated by MIR137.
With an increased understanding of the underlying mechanisms of schizophrenia, scientists will have opportunities to develop new therapeutic strategies and work towards the future goal of individualized treatment. There are many indications that the number of identified genetic risk variants will increase substantially in the near future.
“Successful genetic research requires large study samples with well-matched control subjects. The national registers at the Swedish National Board of Health and Welfare are unique resources which enables nation-wide collections of blood samples, which in turn allows for this type of study”, says Christina Hultman.
The study was funded by the Karolinska Institutet, Karolinska University Hospital, the Swedish Research Council, the Stockholm County Council, the Söderström Königska Foundation, NIMH and the Stanley Center for Psychiatric Research.
Anna Kähler, Christina Hultman, Patrick F Sullivan, and colleagues
Nature Genetics, online 25 August 2013, doi:10.1038/ng.2742
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