WIKIMEDIA, POPULAR SCIENCEResearchers trying to solve the genetic puzzle of schizophrenia have long known that they face a devilishly complex task. Two studies published yesterday (January 22) in Nature now give some insight into the mutations that can trigger the neuropsychiatric disease, at the same time revealing some of the intricacies of its genetics.
“In the beginning of doing this, nobody thought that genetics would lead to anything, that you would ever get genetic data that was meaningful,” coauthor Pamela Sklar of the Icahn School of Medicine at Mount Sinai told Bio-IT World. “It’s clear that we are making progress in understanding the genetics. I think of it as building the foundation.”
In one paper, an international team sequenced the exomes of more than 2,500 people with schizophrenia and more than 2,500 healthy controls. The researchers found rare, disruptive mutations in the genomes of people with schizophrenia, and many of them in genes related to neuronal signaling. The researchers did not find any single gene that raised the risk of schizophrenia on its own. In the second paper, an overlapping team sequenced the exomes of 623 sets of parents and children with schizophrenia. The researchers found that mutations that arose for the first time in children with schizophrenia overlapped with genes that have been implicated in autism spectrum disorders and in genetic pathways related to synapse formation and synaptic transmission.
“Looking for individual changes to the chemical composition of genes, we found what we predicted,” coauthor Michael O’Donovan of Cardiff University told The Conversation. “Even small new mutations were not randomly occurring, but were concentrated in a relatively small number of genes that are crucial to the way nerve cells communicate across synapses.”
Elizabeth Tunbridge of Oxford University, who was not involved in either study, told The Conversation that the papers’ findings are “reassuringly consistent with existing research.”
“Everything about schizophrenia that we’ve ever learned is that it’s really quite genetically complex,” Sklar told Bio-IT World. “We’re learning now is that the rare variants are just as complex as everything else.”