De Novo Single Nucleotide Variants Have Roles in Schizophrenia

Rare, large, de novo (i.e., not present in either parent) copy number variations, found in thousands of genes, are known to increase risk for schizophrenia (NEJM JW Psychiatry Sep 8 2008), but less has been known about single nucleotide variants (SNVs).

To learn more, researchers genotyped 617 parent–child trios, in which the child had been hospitalized for schizophrenia or schizoaffective disorder; exome sequencing was used to examine SNVs that were synonymous (no change in function) or nonsynonymous (loss of function; i.e., stop transcription [which truncates transcribed proteins], frameshift [which begins transcription at alternative sites], or splice [which produces alternative transcription lengths]).

Mutations in probands increased with…