###### Abstract  
Schizophrenia patients commonly suffer from sleep disorders which are associated with acute disease severity, worsening prognoses and a poorer quality of life. Research is attempting to disentangle the complex interplay between schizophrenia and sleep disturbances by focusing not only on demographic and clinical characteristics, but also on the identification of genetic factors. **Methods:** Here, we performed a systematic literature review on the topic of genetic variations in sleep-disordered schizophrenic patients in an attempt to identify high quality investigations reporting scientifically sound and clinically useful data. For this purpose, we conducted a thorough search of PubMed, ScienceDirect and GoogleScholar databases, according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol. **Results:** Our search yielded 11 eligible studies. Certain genetic variations were reported to be associated with schizophrenia-related sleep disorders. Antipsychotic-induced restless legs syndrome was linked to polymorphisms located on _CLOCK_, _BTBD9_, _GNB3_, and _TH_ genes, clozapine-induced somnolence was correlated with polymorphisms of _HNMT_ gene, while insomnia was associated with variants of the _MTNR1_ gene. **Conclusions:** There are significant genetic associations between schizophrenia and co-morbid sleep disorders, implicating the circadian system, dopamine and histamine metabolism and signal transduction pathways.  
Keywords:schizophrenia; sleep disorders; genes; polymorphisms; insomnia; circadian; somnolence; restless-legs syndrome +
Footnote †: journal: Medicalcontinuity and architecture. However, most studies agree that sleep disturbances do not constitute a mere epiphenomenon [7], but rather, represent an integral part of schizophrenia's pathogenesis which is causally linked to the emergence or the precipitation of psychotic symptoms [8; 9; 10].  
Given that both schizophrenia and sleep disorders have been linked to dysfunction in specific neural circuits including dopaminergic and serotonining pathways [10], and that both are characterized by a strong genetic component with shared genetic loci [11; 12], research is increasingly focusing on detecting genetic variations which are associated with their co-occurrence. While relevant investigations provide evidence regarding the existence of specific gene polymorphisms in sleep-disordered schizophrenic patients, these studies are characterized by great variability in terms of sleep disorder classification and candidate genes. More specifically, sleep disorders constitute a constellation of heterogeneous conditions with unique epidemiological, clinical, physiological and genetic features [13]. Schizophrenic patients report various patterns of disordered sleep, mainly insomnia, restless legs syndrome (RLS) and obstructive sleep apnea syndrome [10]. For this reason, a comparison of studies will not lead to solid conclusions unless it is based on an integrated and analytic approach. A similar approach to the interpretation of genetic findings is also required, given that modern advances in molecular biology have led to the mapping of a significant number of genes which have been implicated in schizophrenia and sleep pathophysiology [12; 14]. Reported findings would therefore provide more clinically relevant information if they could be clustered and summarized in a way that would link them to distinct patterns of neurophysiological and intracellular pathways.  
In this context, we have conducted a systematic review of studies searching for genetic variations which are associated with sleep disorders in schizophrenic patients. Our primary aim was to integrate existing findings into a comprehensive set of evidence-based knowledge. Furthermore, we sought to detect areas of scientific ambiguity and define directions for future research. To our knowledge this is the first systematic review focusing on this topic.