Some questions in science are solved by a few pioneers toiling in their laboratories, but others depend on huge international teams. In the past several years, Big Science has come to schizophrenia research in the form of large "genome-wide association studies" (GWAS). In the latest news from this effort, published online today in the journal Nature, more than 100 regions of the genome show "association" with schizophrenia, the genetic version of smoke indicating the strong likelihood of fire. In genetic terms, the smoke could signal a genetic variation that changes a person's odds of developing schizophrenia.
More than 80 institutions participating in the Psychiatric Genomics Consortium (PGC) contributed blood samples from nearly 37,000 people with schizophrenia and more than 113,000 control subjects without mental illness, making this one of the largest biomedical experiments ever, and certainly the largest in mental illness. “The fact that we were able to detect genetic risk factors on this massive scale shows that schizophrenia can be tackled by the same approaches that have already transformed our understanding of other diseases,” said the paper’s senior author and 2012 Foundation Lieber Prizewinner for Outstanding Achievement in Schizophrenia Research Michael O’Donovan, M.D., Ph.D., of Cardiff University in the United Kingdom.
The research team identified 128 independent genetic associations spanning 108 different “loci,” or areas of the genome where variations in sequence were associated with schizophrenia. Eighty three of these loci had not been previously identified. Greater association was found with genes that are expressed in the brain and also among genes with important roles in the functioning of the immune system. This work confirms some previous hypotheses about genetic associations and also offers some entirely new insights.
National Institute of Mental Health Director Thomas Insel, M.D. (Foundation 2014 Productive Lives Awardee) wrote in a blog post today: "This recent progress is indeed a giant step forward for the field, but it is one step on a long journey. In truth, we do not have a rapid means to pivot from a genomic association to a target for treatment development. And complex genetic disorders, by definition, will not yield a simple genetic test for diagnosis. But these findings do suggest a way forward. By identifying the molecular pathways of risk, using cell-based studies with those pathways manipulated, and filling in the gap between molecular neuroscience and brain function, these new findings become part of the foundation for translational science.”
The work was done by the Schizophrenia Working Group of the PGC, which was set up to conduct these sorts of collaborations. Although hundreds of researchers contributed their work to the project, of special note are the senior authors Dr. O'Donovan, who led the group that managed the study; 2010 NARSAD Distinguished Investigator Grantee Patrick Sullivan, M.D., of the University of North Carolina, who has spearheaded the PGC; and Mark Daly, M.D., whose team at the Broad Institute, including first author Stephan Ripke, M.D., did most of the statistical analysis. In addition to these researchers, a number of other NARSAD Grantees and Foundation Scientific Council Members were involved in this large study.