Schizophrenia Genetics Untangled
January 22, 2014

Scientists Begin To Untangle The Genetic Mutations Behind Schizophrenia

Brett Smith for - Your Universe Online

An international team of researchers has found a system of genetic mutations and signature patterns underlying schizophrenia, according to two studies published this week in the journal Nature.

One study examined gene sequences from 2,500 patients with schizophrenia and 2,500 healthy volunteers. The other study looked for mutations in protein coding genes from over 600 schizophrenia individuals with the disorder along with their unaffected mothers and fathers.

Both studies pointed to the cumulative effects of many genes that play a role in the mental disorder – a phenomenon known as polygenicity. The studies also indicated that genetic changes tended to group into select networks of functionally-related genes.

"Despite the considerable sample sizes, no individual gene could be unambiguously implicated in either study. Taken as a group, however, genes involved in neural function and development showed greater rates of disruptive mutations in patients," said Shaun Purcell, a researcher at the Broad Institute of MIT and Harvard who was involved in both studies. "That finding is sobering but also revealing: it suggests that many genes underlie risk for schizophrenia and so any two patients are unlikely to share the same profile of risk genes."

Both studies said relevant mutations were spread across many genes, with comparable patterns in the allocation of mutations across gene networks. Many of the relevant genes shared common functions, such as synaptic function involving signaling between cells in the brain and the cytoskeletal (ARC) protein complex, which plays a role in learning and memory functions.

"From a scientific standpoint, it's reassuring to see different methods of studying the genetics of schizophrenia converge on the same sets of genes. These varied approaches are pointing toward the same underlying biology, which can be followed up in future research," said Steven McCarroll, a professor in genetics at Harvard Medical School and co-author on both papers.

The researchers also found significant overlap between mutations found in schizophrenia and mutations connected to autism and cognitive disability.

The study authors from both papers noted that genome sequencing will continue to be a prominent tool in the study of schizophrenia and called for additional research surrounding the genetics behind the condition.

"Few facts have been firmly established about the molecular or cellular causes of schizophrenia, and that's because many traditional scientific approaches can't be used to study the disorder: you can't grow it in a dish, and there aren't very good animal models for it," McCarroll explained.

"We think that genomes are the path out of the darkness, and that these studies and others like them will ultimately provide the molecular clues we will need to map out the pathophysiology of the disorder."

"The genetic analysis of schizophrenia is yielding remarkably promising results because scientists around the world have worked collaboratively for years to recruit and study the large number of patients and comparison subjects needed to pick out rare genetic variants associated schizophrenia against the staggeringly complex background genetic variation that characterizes humanity. Phrases like 'finding needles in haystacks' do not begin to do justice to this shared global effort," explained Dr. Steven Hyman, director of psychiatric research at the Broad Institute.