Rare Genetic Variants Found to Raise Schizophrenia Risk

Finding the genetic differences that lead to schizophrenia can be notoriously difficult, so the results published Monday in Nature Genetics raised excitement. An international team of researchers located several parts of the genome where mutations increase risk of the mental disorder, by many orders of magnitude.

The team of 260 researchers, led by Jonathan Debat, PhD, of the University of California at San Diego, looked at 2 sets of genomes: first, they looked at 21,094 people with schizophrenia, and then at 20,227 people without the disease. The work pinpointed 8 locations on the genome with “copy number variants,” which are associated with schizophrenia risk. These mutations are areas where the DNA sequence is either duplicated or deleted, involving 1 gene or dozens.

Previously, Sebat and his team at UC San Diego School of Medicine have found that these variations in the genome that lead to psychiatric disorders, and copy number variants in particular, are found more often with people who have schizophrenia than in the rest of the population. The errors in the DNA affect the function of the synapses, the connections between the brain cells that carry chemical messages from one part of the brain to the other.

As important as these findings are, the copy number variants the team uncovered only account for a fraction of schizophrenia cases (1.4%). The researchers know that many more variants linked to schizophrenia exist, and more work will be needed to find them.

“This study represents a milestone that demonstrates what large collaborations in psychiatric genetics can accomplish,” Sebat said. “We’re confident that applying this same approach to a lot of new data will help us discover additional genomic variations and identify specific genes that play a role in schizophrenia and other psychiatric conditions.”