Increased Risk for Nonfamilial Schizophrenia from De Novo Mutations

Single nucleotide polymorphisms (SNPs) in sporadic (nonfamilial) schizophrenia have been less studied than genetic copy number variants (CNVs) in familial schizophrenia. To identify de novo mutations, these investigators sequenced 795 exomes (i.e., coding regions) from 231 schizophrenia trios (probands and their parents; 146 Afrikaner and 85 U.S. trios) and 34 healthy Afrikaner control trios. By identifying mutations occurring in probands but not their parents, researchers could select nonfamilial cases. The investigators examined synonymous substitutions (which do not alter the protein), nonsynonymous substitutions (which do change the protein), and loss-of-function mutations.

The ratio of nonsynonymous to synonymous SNPs was significantly …