Single Changes in Two Genes Can Double Schizophrenia Risk

In an article published in the most recent issue of Neuron, a team from Johns Hopkins identifies two genetic markers which, in the right combination, can more than double an individual’s risk of one day developing schizophrenia. This finding is especially noteworthy given the difficulty geneticists have had unraveling the complex genetic interraltions that lead to diseases like schizophrenia or autism.

The gene DISC1 has long been implicated in the development of schizophrenia. Drastic changes to this gene alone can substantially increase that risk, but most schizophrenics don’t demonstrate such changes. Instead, the Johns Hopkins researchers focused on small changes which could be compounded by other small changes to different genes. Together, these changes have a synergistic effect many times larger than each change on its own.

By examining the genetic code of thousands of schizophrenia patients in the National Institutes of Health’s Genetic Association Information Network, the authors were able to identify the FEZ1 gene as having the largest synergistic effect. Specifically, they looked at four single-letter changes on FEZ1 and found that although they did nothing to increase schizophrenia risk on their own, when an individual already had a mutated DISC1 gene, the changes to FEZ1 were suddenly activated. One of the FEZ1 changes contributed to a 250 percent increase in the likelihood of developing the disease.

Hopefully, say the study’s authors, by continuing to map out the interactions that combine to cause mental disease, medical science will be able to create new medications and other treatments that specifically target those interactions to prevent or mitigate the risks of those illnesses.

Source: MedicalNewsToday.com and Johns Hopkins University

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