Schizophrenia risk linked to common genetic variants

Genetic variants that contribute to the risk of schizophrenia are present in everyone. Flickr/Akelei van Dam

A quarter of the risk for developing schizophrenia can be traced to genetic variations that are common in the general population, a study by Queensland researchers has found.

A new method of genetic analysis developed by The University of Queensland’s Queensland Brain Institute, in conjunction with The University of Queensland Diamantina Institute and the Queensland Institute of Medical Research, found that all people carry genetic variants that contribute to the risk of schizophrenia.

But only people who carry many of those variants together are at substantial risk of being affected.

The chronic disorder, characterised by persistent delusions and hallucinations, affects about one person in 100 at some point in their lives and usually strikes in late adolescence or early adulthood.

The latest research into the disease, published in the journal Nature Genetics, has shed light on its elusive genetic underpinnings, said the study leader, Associate Professor Naomi Wray from the Queensland Brain Institute.

“Not long ago people talked about finding "the gene” for schizophrenia, then the “handful of genes”. Our research implies there are many genetic factors acting together, and together with environmental factors,“ Professor Wray said.

"If we all carry some risk variants then our systems are robust to their effects - for example other pathways may compensate. Our results suggest that affected people may carry a burden of risk variants that means compensatory mechanisms can no longer cope.”

The researchers compared genetic variations in DNA known as single-nucleotide polymorphisms across 9,087 people who had schizophrenia and 12,171 people who did not.

They found that 23% of liability for the brain disorder could be traced back to a set of variations, most of which are common in the general population. The variance was shared equally between men and women.

According to Professor Naomi Wray, this suggests that we all carry genetic risk variants for schizophrenia, but that the disease only emerges when the burden of variants, in combination with environmental factors, reaches a certain tipping point.

Cannabis use is recognised as one environmental factor that contributes to the risk of developing schizophrenia.

Paul Fitzgerald, a Professor of Psychiatry at Monash Alfred Psychiatry Research Centre, said the past 10 years of research into schizophrenia had been characterised by “high hopes followed by disappointing results. But this study provides some novel and promising guidelines for how we can understand the causes of schizophrenia and where we go from here.”

The findings suggested that variations in many hundreds of genes contributed to the risk of developing schizophrenia, Professor Fitzgerald said. “Variations in many of these genes, however, are frequently found across all people and will be possible targets for study to help develop new treatments.

"However, before this can occur we need to individually identify this set of genes and this is likely to take studies with up to 50,000 patients and a similar number of controls.”