A candidate biological network formed by genes from genomic and hypothesis-free scans of suicide.

Abstract Information about genes and the biology of suicidal behavior (SB) is noisy due to heterogenous outcomes (suicide attempts or deaths), as well as many different genes and overlapping biological processes implicated. One approach to test the unbiased biological coherence of disease genes, is to use genes from hypothesis-free genetic scans and to investigate if they aggregate close to each other in cellular gene and protein interaction networks (“interactomes”). Therefore, we used network methods to study the biological coherence among genes (n = 229) from genome-wide association studies (GWAS) and whole exome sequencing (WES) of suicide outcome. Results showed that the suicide GWAS+WES genes has significant aggregation in three major interactome database assemblies, a hallmark of biological similarity and increased likelihood of being involved in the same outcome (suicide). This pinpointed e.g. genes on chromosome 19, which are also associated with lipid metabolism, schizophrenia and bipolar disorder. We identified a subset of GWAS+WES “core” genes (n = 54) which are the most proximal to each other in the context of three interactome assemblies, and present a candidate network module of suicide which is specific for nervous system tissues. The n = 54 most proximal “core” genes showed overrepresentation of synaptic and nervous system development genes, as well as network paths to other SB genes having increased evidence diversity. Overall, results suggested the existence of a coherent biology in suicide outcome and provide unbiased biological support concerning links to other SB genes, as well as e.g. bipolar disorder, excitatory/inhibitory function and ketamine treatment in SB.