Exome sequencing has a low diagnostic yield in schizophrenia, according to research published in Schizophrenia Bulletin.

Investigators reviewed data from the Bulgarian Trio Sequencing study, which comprised trios of individuals (patients with schizophrenia and both of their parents) who underwent exome sequencing. They screened 591 of these trios for any variants (dominant or recessive) that would be considered disruptive or damaging and pathogenic for schizophrenia.

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Investigators identified 4 cases with disruptive de novo variants in the genes SETD1A, POGZ, SCN2A, and ZMYND11 and 1 damaging de novo variant of uncertain significance in NRXN1. Investigators found 21 disruptive variants in parents that had not been transmitted to the patients. They also found 467 damaging variants that had been inherited by patients but another 429 variants in parents that had not been transmitted, and none of these were clinically significant.

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Investigators noted that “the diagnostic yield for exome sequencing of known neuropsychiatric genes in this sample is about 1%, lower than the expected yield for testing for pathogenic [copy number variants] of 3% or more and much lower than the yield of 40% obtained in severe developmental disorders.”

“Disruptive and damaging variants seen in known neuropsychiatric genes should not be automatically assumed to have an etiological role if observed in a patient with schizophrenia,” investigators concluded.


Balakrishna T, Curtis D. Assessment of potential clinical role for exome sequencing in schizophrenia [published online May 21, 2019]. Schizophr Bull. doi:10.1093/schbul/sbz057

This article originally appeared on Psychiatry Advisor