Published: 26-08-2013 00:00 | Updated: 14-02-2014 16:27

New risk genes for schizophrenia discovered

Research on the underlying causes of schizophrenia are now taking a big leap forward, when scientists at Karolinska Institutet and colleagues in the United States have identified 13 new genetic variants that increase the risk for schizophrenia. 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. 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.


Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
Ripke S, O'Dushlaine C, Chambert K, Moran J, Kähler A, Akterin S, et al
Nat. Genet. 2013 Oct;45(10):1150-9