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New Study Opens Window on Mutations in Genetic Architecture of Schizophrenics

  New Study Opens Window on Mutations in Genetic Architecture of Schizophrenics

Photo: Catharine E. Krebs

While past research has shown the impact of commonly occurring genetic variants on a person’s risk of developing schizophrenia, a new UCLA study has focused instead on rare coding mutations that affect protein function. It found that people with schizophrenia have a higher-than-normal share of these mutations.

“While we cannot point to specific mutations that play a causal role in schizophrenia, we show that schizophrenia patients collectively have more of these mutations than unaffected individuals,” says Loes Olde Loohuis, postdoctoral fellow at UCLA’s Center for Neurobehavioral Genetics in the Jane and Terry Semel Institute for Neuroscience and Human Behavior at UCLA.

“Genes that are affected by these mutations play a key role in fetal brain development,” says Roel Ophoff, PhD, professor of psychiatry and human genetics and principal investigator at the Center for Neurobehavioral Genetics. “Our finding further supports the hypothesis that schizophrenia is a disorder that may originate during the early stages of brain development.”

Dr. Ophoff has conducted research on the genetic basis of schizophrenia for the past decade. He also is one of the founding members of the Psychiatric Genomics Consortium’s schizophrenia study group. The consortium is an international collaboration of researchers investigating the genetics of schizophrenia and related disorders. Dr. Ophoff and his colleagues used an array-based technology to screen for 250,000 DNA coding variants in more than 1,000 schizophrenia patients from the Netherlands and compared these samples to those from unaffected individuals. They found that the patients with schizophrenia had more of these variants than patients without schizophrenia. The researchers confirmed these findings in another cohort consisting of more than 13,000 schizophrenia patients and control subjects from the U.K.

“Even though it’s well-known that schizophrenia has a large genetic component, the specific biological mechanisms at work are not well-understood,” Dr. Ophoff says. “Our research shows that rare coding variants throughout the human genome also contribute to this complex genetic architecture.”

“Genome-wide Burden of Deleterious Coding Variants Increased in Schizophrenia,” Nature Communications, July 9, 2015


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