Schizophrenia is a serious mental illness affecting 1 in every 100 people at some point during their lives. Genetic factors are thought to account for more than 70% of all cases, and scientists have long sought to identify those genetic markers in an effort to predict who is predisposed to the disease so that they can avoid triggers and perhaps onset. Recently, two-large scale, multi-national collaborations netted results that brought the medical community closer to that goal by identifying sections of the human genome that, when deleted, can elevate the risk of developing schizophrenia 15-fold, as compared to the general population.
The International Schizophrenia Consortium (ISC)1, a collaboration of researchers from 12 institutions in Europe, the United States and Australia, studied the genomes of 3,391 patients with schizophrenia, looking for a specific type of genetic error called a copy number variation, in which a section of the genome is deleted or duplicated.
The SGENE consortium2, made up of 18 institutions across Europe, the United States and China, catalogued all the copy number variations between 15,000 parents and their children, and then looked for matches to these variations in nearly 5000 schizophrenia patients.
Both groups documented genetic deletions associated with schizophrenia in the same three locations: Two new discoveries on chromosomes 1 and 15, and confirmation of the previously connected chromosome 22. The SGENE collaboration located an additional deletion on chromosome 15, and the ISC determined that people with schizophrenia are more likely to carry rare chromosomal structure changes than are those without the disease. Both groups also verified that these deletions confer a greatly increased risk of schizophrenia (somewhere between 3 and 15 times greater for different deletions), but that each occurs in only around 1% of the population.
Although these findings don’t completely explain the genetic basis of schizophrenia, the replication of the findings in two distinctly separate studies is important. “The fact that there are two independent studies that come at the problem from different angles and using different methodologies is fantastic for psychiatric genetics,” says Pamela Sklar of Harvard Medical School in Cambridge, Massachusetts, part of the ISC study.
Jonathan Flint, who studies the genetic basis of psychiatric diseases at the Wellcome Trust Centre for Human Genetics at the University of Oxford, agrees that the results are a major advance, but points out that converting these findings into a better understanding of the biology of schizophrenia will take a lot more work. “The genetic changes on chromosome 22 have been known for some time,” he says, “but the exact genes that cause the increase in risk still remain unclear.”
Nevertheless, these are the first deletions associated with schizophrenia to be identified in such a large sample across several populations. Since schizophrenia is a disorder affecting thoughts and emotions, it is a devastating disease that is little understood and is difficult to diagnose. These findings shed light on its causes and provide a first component to a molecular test to aid in clinical diagnosis and intervention.