Strongest single gene conclusively implicated in schizophrenia

An international consortium of researchers, led by a team at the Wellcome Trust Sanger Institute, has discovered conclusive evidence for the involvement of a gene called SETD1A in schizophrenia. Damaging changes to this gene, which occur rarely, increase the risk of schizophrenia 35-fold and also increase risk for a wide range of neurodevelopmental disorders.

The research establishes for the first time that single-letter changes to the DNA code of one gene can have such substantial effect on the risk of schizophrenia, leading to a step forward in understanding the biology and potential treatments of schizophrenia.

Schizophrenia is a devastating mental illness affecting nearly 300,000 people in the UK, but knowledge of what causes it is very limited. Previous studies of families have shown that genetics plays an important role in the disorder.

Researchers found that mutations that remove the function of the SETD1A gene are almost never found in the general population, and affect less than 1 in 1000 people with schizophrenia. While this gene explains only a very small fraction of all schizophrenia patients, it provides an important clue to the wider biology of the disorder.

“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. 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.”

Dr Jeff Barrett, lead author and Group Leader at the Wellcome Trust Sanger Institute
In the largest study of its kind to date, the genome sequences of more than 16,000 people from the UK, Finland and Sweden were analysed, including those from 5,341 people who had been diagnosed with schizophrenia.

Damage to the SETD1A gene was found in 10 of the patients with schizophrenia, and surprisingly was also found in 6 other people with other developmental and neuropsychiatric disorders such as intellectual disability. This finding that the same gene is involved in both schizophrenia and developmental disorders shows that they may share common biological pathways. Sanger Institute