The role of <i>trans</i> -acting factors in the pathogenesis of common psychiatric disorders

According to the omnigenic model for the inheritance of common traits proposed by Jonathan Pritchard's group in 2017, there are a very large number of genetic variants underlying common traits spread across the genome. Causal variants are of two types: core genes that have direct roles in disease pathogenesis that contribute only a small amount to total heritability and peripheral genes that are much more in number than core genes and that cumulatively contribute maximally to trait heritability. The same group proposed in 2019 that peripheral genes have indirect effects by acting in <i>trans</i>. The authors propose that most heritability is due to weak <i>trans</i>-expression quantitative trait loci (<i>trans</i>-eQTL) single nucleotide polymorphisms (SNPs) whose effects are mediated by peripheral genes that influence the expression of core genes. In 2018, we provided evidence for an epigenetic-based omnigenic model for the inheritance of common psychiatric disorders. In the current article, we discuss the possible role of genes underlying <i>trans</i>-acting factors, namely, non-coding RNAs and transcription factors, in the pathogenesis of common psychiatric disorders.