## 3 Results
### Associations between Genetic Variations and Specific Sleep Disorders  
According to a series of well-designed studies in a sample of Korean schizophrenic patients on antipsychotic medications, treatment-induced RLS was found to be significantly associated with rs2412646, rs1801260 and rs2412646-rs1801260 haplotype of _CLOCK_ gene (Circadian Locomotor Output Cycles Kaput), as well as rs9357271 alleles' frequency and rs3923809-rs9357271 haplotype of _BTBD9_ (BTB Domain Containing 9) gene. Additionally, [PERSON] et al. (2009) genotyped the same sample of patients and found that the rs6356 polymorphism of _TH_ gene (Tyrosine Hydroxylase) is associated with increased frequency of RLS only in female subjects [18]. In a similar vein, the probability of antipsychotic-induced RLS was linked to the presence of the C allele of rs5443, of _GNB3_ gene (G Protein Subunit Beta 3) [19]. In contrast, in the same group of patients, the authors failed to detect any significant associations between drug-induced RLS and specific polymorphisms of _MEIS1_ (Myeloid Ecotropic Viral Integration Site 1 Homology), _MAOA_ (Monoamine Oxidase Type A), _MAOB_ (Monoamine Oxidase Type B), _DRD1_ (Dopamine Receptor D1), _DRD2_ (Dopamine Receptor D2), _DRD3_ (Dopamine Receptor D3) and _DRD4_ (Dopamine Receptor D4) genes [20; 21; 22]. Likewise, the frequencies of rs3923809 polymorphism of the _BTBD9_ gene, as well as the rs2305160-rs6725296 haplotype of _NPAS2_ gene (Neuronal PAS Domain Protein 2), were not significantly different among patients with and without RLS [23; 24].  
In another study with a larger sample of Korean patients and a healthy control group, the presence of insomnia was associated with rs2119882 polymorphism of _MTNR1A_ gene (Melatonin Receptor 1A) [25], while hypersomnia did not correlate with any _MTNR1A_ polymorphism.  
In a recent study of clozapine treated Finnish patients, rs1455156, rs2737385, rs1050891, rs4245861, rs464633, rs1455158, rs14155157 and rs1050900 polymorphisms on _HNMT_ gene (Histamine N-Methyltransferase) were associated with daytime somnolence/sedation. Additionally, a correlation was revealed between clozapine-induced somnolence and rs2737385 polymorphism on _HNMT_ gene, rs1552498 and rs17034063 polymorphisms on _HRHI_ gene (Histamine Receptor H1), as well as rs697738 polymorphism on _AOC1_ gene (Amine Oxidase Copper Containing 1). In a previous study using the same group of participants, TT genotype of rs2470890 polymorphism located on _CYPIA2_ gene (Cytochrome P450 Family 1 Subfamily A Member 2), was associated with a significantly greater overall side-effect frequency. However, statistical analysis failed to reveal any significant associations between the above genotype and clozapine-induced daytime somnolence [26]. Likewise, [PERSON] et al. (2013) found no significant associations between sleepiness and the variants of several genes which are implicated in risperidone pharmacokinetics and pharmacodynamics, although there was a negligible trend towards a higher frequency of sleepiness in patients carrying the C allele of rs6280 polymorphism, located on _DRD3_ gene (dopamine receptor D3) [27].  
IPA analysis results are shown in Figure 2. Our analysis indicated that _GNB3_ participates in a variety of signaling pathways, such as protein kinase A, IL-8, IL-1, Gaq, phospholipase C, Tec kinase, G beta gamma, a-adrenergic, Gas, Gai, opioid, and glutamate receptor signaling, while _MTNR1A_ in melatonin, _BTBD9_ in dopamine signaling, _HNMT_ in histamine degradation, _TH_ in protein kinase A and opioid signaling pathway and _CLOCK_ in circadian rhythm, adipogenesis and sirtuin signaling pathway.