Evolutionarily recent retrotransposons contribute to schizophrenia

Abstract

Abstract Transposable Elements (TEs) are mobile genetic elements that constitute half of the human genome. Recent studies suggest that polymorphic non-reference TEs (nrTEs) may contribute to cognitive diseases, such as schizophrenia, through a cis-regulatory effect. The aim of this work is to identify sets of nrTEs putatively linked to an increased risk of developing schizophrenia. To do so, we inspected the nrTE content of genomes from the Dorsolateral Prefrontal Cortex of schizophrenic and control individuals, and identified 38 nrTEs which possibly contribute to the emergence of this psychiatric disorder. Furthermore, we performed in silico functional inferences and found, for instance, that 9 of the 38 nrTEs act as expression/alternative splicing quantitative trait loci (eQTLs/sQTLs) in the brain, suggesting a possible role in shaping the human cognitive genome structure. Therefore, to our knowledge, this is the first attempt at identifying polymorphic nrTEs that can contribute to the functionality of the brain. Finally, we suggest that a neurodevelopmental genetic mechanism, which involves evolutionarily young nrTEs, can be the key to understanding the ethiopathogenesis of this complex disorder.