Chronotype and sleep quality as a subphenotype in association studies of clock genes in mood disorders

Genetic background and clinical picture of mood disorders (MD) are complex and may depend on many genes and their potential interactions as well as environmental factors. Therefore, clinical variations, or endophenotypes, were suggested for association studies. The aim of the study was to investigate association between the chronotype (CH) and quality of sleep characteristics with polymorphisms CLOCK, ARNTL, TIMELESS and PER3 genes in MD. We included a total sample of 111 inpatients and 126 healthy controls. To assess CH we applied Morningness-Eveningness Questionnaire (MEQ). Additionally, we defined the quality and patterns of sleep using The Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). We applied Kruskal-Wallis test to determine associations. The main positive findings refer to associations between selected polymorphisms and: 1) chronotype with the ARNTL gene (rs11824092 and rs1481892) and the CLOCK (rs1268271), 2) sleep duration with the CLOCK gene (rs3805148) and the TIM gene (rs2291739), 3) daytime dysfunction with the PER3 gene (rs228727, rs228642, rs10864315), 4) subjective sleep quality with the ARNTL gene (rs11824092, rs1982350), 5) sleep disturbances with the ARNTL gene (rs11600996). We also found the significant epistatic interactions between polymorphism of the PER3 gene (rs2640909) & the CLOCK gene (rs11932595)and following sleep quality variables: sleep duration, habitual sleep efficiency and subjective sleep quality. The present study suggests a putative role of the analyzed clock genes polymorphisms in chronotype in the control group and in sleep quality disturbances in the course of MD. The results indicate that PSQI variables can be used to refine phenotype in association studies of clock genes in MD.