Investigators at the Lieber Institute for Brain Development, including Director and CEO Daniel R. Weinberger, M.D., and Richard E. Straub, Ph.D.—as members of the Schizophrenia Working Group (SWG) of the Psychiatric Genomics Consortium—participated in the largest genetic study of schizophrenia to date. The mass collaborative effort of the multinational team of scientists comprising the SWG, hailing from 80 different institutions, yielded important new insights about the heritability of schizophrenia that were published on July 24, 2014 in the journal Nature.
The researchers studied DNA from over 150,000 individuals, of whom nearly 37,000 were people diagnosed with schizophrenia. The others served as control samples. They identified 108 locations throughout the human genome—so-called “genetic loci”—where DNA variations contribute to the risk of having schizophrenia. Eighty three of these loci had not been previously identified and importantly, the team showed that these variations, which are departures from the standard reference genome, are common across humans. They also found that these variations “converge upon genes that are expressed in certain tissues and cell types.”
These findings point scientists in new directions on their quest to identify diagnostic criteria for the illness and to develop more effective interventions and treatments.
Many of the genes in the 108 loci are most active in the brain. A few serve to substantiate hypotheses scientists have long had about schizophrenia. For example, one gene encodes the receptor (the D2 dopamine receptor or DRD2) that is blocked with current treatment of antipsychotic medications, medications that alleviate to a varying extent the so-called “positive symptoms” of schizophrenia such as hallucinations and delusions. Also, some genes identified are involved in the mechanism by which the neurotransmitter glutamate functions in the brain, another common therapeutic target in schizophrenia. Interestingly, the study identified variations in genes that are involved in the proper function of the immune system, supporting a speculated link between the immune system and schizophrenia. Many other findings have the potential to provide entirely new insights into the complex causes of schizophrenia.
Through this large-scale collaborative effort, after many years of exploring in smaller sample sizes, scientists have arrived at a reliable signal of common variations contributing to risk for schizophrenia. It does not paint a simple picture, but it does offer new insights and points scientists in new directions on their quest to identify diagnostic criteria for the illness (how it can be successfully predicted before it manifests) and to develop more effective interventions and treatments.