An international team led by a UC San Diego School of Medicine professor announced Tuesday that mutations in eight regions of the human genome dramatically increase the risk of schizophrenia.
The study, published in the journal Nature Genetics, found that the mutations known as copy number variants — deletions or duplications of the DNA sequence — occurred more frequently in genes involved in the function of synapses, the connections between brain cells that transmit chemical messages.
Researchers with the Psychiatric Genomics Consortium, led by UCSD’s Jonathan Sebat, analyzed the genomes of more than 41,000 people in the largest study of its kind to date.
“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.”
The mutations observed by the researchers increase schizophrenia risk between four- and 60-fold, according to UCSD.
A copy number variant may affect dozens of genes, or it can disrupt or duplicate a single gene.
This type of variation can cause significant alterations to the genome and lead to psychiatric disorders, said Sebat, who is a professor and chief of the Beyster Center for Genomics of Neuropsychiatric Diseases at the UCSD School of Medicine.
Sebat and other researchers previously discovered that relatively large copy number variants occur more frequently in schizophrenia than in the general population.
In the latest study, Sebat teamed up with more than 260 researchers from around the world to analyze the genomes of more than 21,000 people with schizophrenia and over 20,000 people without schizophrenia.
The researchers said they are still missing many variants, so more analyses will be needed to detect risk variants with smaller effects.
The consortium is primarily funded by the National Institutes of Health.
—City News Service