Genetic origins of suicidality? A synopsis of genes in suicidal behaviours, with regard to evidence diversity, disorder specificity and neurodevelopmental brain transcriptomics.

With regard to suicidal behavior (SB) genetics, many novel genes have been implicated over the years, in particular by a variety of hypothesis-free genomic methods (e.g. GWAS and exome sequencing). In addition, many novel SB gene findings appear enigmatic in their biological relevance and have weak statistical support, e.g. lack direct replications. Adding to this is the comorbidity between psychiatric disorders and SB. Here we provide a synopsis of SB genes, by prioritization of 106 (out of ~2500) genes based on their highest level of evidence diversity across mainly five genetic evidence types (candidate/GWAS SNP, CNV, linkage and whole exome sequencing), supplemented by three functional categories. This is a representative set of both old and new SB gene candidates, implicated by all kinds of evidence. Furthermore, we define a subset of 40 SB "specific" genes, which are not found among ~3900 genes implicated in other neuropsychiatric disorders, e.g. Autism spectrum disorders (ASD) or Schizophrenia. Biological research of suicidality contains a major developmental focus, e.g. with regard to the gene-environment interactions and epigenetic effects during childhood. Less is known about early (fetal) development and SB genes. Inspired by huge efforts to understand the role early (fetal) neurodevelopment in e.g. ASD by using brain transcriptomic data, we here also characterize the 106 SB genes. We find interesting spatiotemporal expression differences and similarities between SB specific and non-specific genes during brain neurodevelopment. These aspects are of interest to investigate further, to better understand and counteract the genetic origins suicidality.

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Copyright © 2020. Published by Elsevier B.V.

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Conflicts of interest The authors declare they have no conflicts of interest.