Single Gene Implicated in Schizophrenia Cases

Single-letter changes to the DNA code of a specific gene increase the risk of schizophrenia 35-fold, according to a study by an international consortium of researchers in the online Nature Neuroscience. Changes to the gene, called SETD1A, also increase risk for a range of neurodevelopmental disorders, researchers found.

“The results were surprising, not only that we found such a high level of certainty that the SETD1A gene was involved, but also that the effects of the gene were so large,” said lead author Jeff Barrett, PhD, group leader at the Wellcome Trust Sanger Institute in Cambridge, UK. “Psychiatric disorders are complex diseases involving many genes, and it is extremely difficult to find conclusive proof of the importance of a single gene. This is a really exciting finding for research into schizophrenia.”

Changes to the SETD1A gene are extremely rare in the general population, according to researchers. Even in people with schizophrenia, they affect less than 1 in 1,000 and, subsequently, explain only a small number of patients.

Researchers analyzed the genome sequences of more than 16,000 people from 3 countries, 5,341 of whom had schizophrenia. SETD1A gene damage affected 10 of the people with schizophrenia, they found, as well as 6 people with intellectual disability and other neurodevelopmental disorders. Consequently, researchers believe schizophrenia may share biological pathways with other development disorders.

“We have a very limited understanding of how schizophrenia arises, and this has hampered attempts to develop new treatments. Current drugs are only effective in alleviating some of the symptoms, can lead to troubling side effects, and are ineffective in a sizeable minority of cases,” said Mike Owen, PhD, director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University, Cardiff, UK.

“Defects in the SETD1A gene, which by itself explains only a small fraction of cases, may guide us towards new pathways that could be targets for therapeutic drugs in a larger number of cases.”

—Jolynn Tumolo

References

  1. Singh T, Kurki MI, Curtis D, et al. Rare loss-of-function variants in SETD1A are associated with schizophrenia and developmental disorders. Nature Neuroscience. 2016;19:571-577.
  2. Strongest single gene conclusively implicated in schizophrenia [press release]. Wellcome Trust Sanger Institute: Cambridgeshire, UK; March 14, 2016.