September 16, 2014
Javier Arnedo, from the Washington University School of Medicine in St. Louis, and colleagues conducted a large genome-wide study involving cases with schizophrenia and controls to examine sets of interacting single-nucleotide polymorphisms (SNPs) that cluster within particular individuals. For each SNP set, they examined the risk of schizophrenia, and tested the replicability in two independent samples. Genomic networks composed of SNP sets sharing SNPs or subjects were identified. Clinical features that cluster in particular cases were identified, and the correlation between SNP sets and distinct phenotypic sets was examined.
The researchers identified 42 SNP sets that were associated with a risk of schizophrenia of ≥70%; ≥81% were confirmed in two independent samples. Seventeen of the SNP networks were disjointed and did not share any SNP or subject; these correlated with distinct gene products and clinical syndromes. Complex associations showing multifinality and equifinality were seen for genotypic networks and clinical syndromes. The interactive networks accounted for more of the risk of schizophrenia than the average effects of all SNPs (24%).
"Schizophrenia is a group of heritable disorders caused by a moderate number of separate genotypic networks associated with several distinct clinical syndromes," the authors write.