Investigation of associations between NR1D1, RORA and RORB genes and bipolar disorder.

Several genes that are involved in the regulation of circadian rhythms are implicated in the susceptibility to bipolar disorder (BD). The current study aimed to investigate the relationships between genetic variants in NR1D1 RORA, and RORB genes and BD in the Han Chinese population. We conducted a case-control genetic association study with two samples of BD patients and healthy controls. Sample I consisted of 280 BD patients and 200 controls. Sample II consisted of 448 BD patients and 1770 healthy controls. 27 single nucleotide polymorphisms in the NR1D1, RORA, and RORB genes were genotyped using GoldenGate VeraCode assays in sample I, and 492 markers in the three genes were genotyped using Affymetrix Genome-Wide CHB Array in sample II. Single marker and gene-based association analyses were performed using PLINK. A combined p-value for the joining effects of all markers within a gene was calculated using the rank truncated product method. Multifactor dimensionality reduction (MDR) method was also applied to test gene-gene interactions in sample I. All markers were in Hardy-Weinberg equilibrium (P>0.001). In sample I, the associations with BD were observed for rs4774388 in RORA (OR = 1.53, empirical p-value, P = 0.024), and rs1327836 in RORB (OR = 1.75, P = 0.003). In Sample II, there were 45 SNPs showed associations with BD, and the most significant marker in RORA was rs11639084 (OR = 0.69, P = 0.002), and in RORB was rs17611535 (OR = 3.15, P = 0.027). A combined p-value of 1.6×10-6, 0.7, and 1.0 was obtained for RORA, RORB and NR1D1, respectively, indicting a strong association for RORA with the risk of developing BD. A four way interaction was found among markers in NR1D1, RORA, and RORB with the testing accuracy 53.25% and a cross-validation consistency of 8 out of 10. In sample II, 45 markers had empirical p-values less than 0.05. The most significant markers in RORA and RORB genes were rs11639084 (OR = 0.69, P = 0.002), and rs17611535 (OR = 3.15, P = 0.027), respectively. Gene-based association was significant for RORA gene (P = 0.0007). Our results support for the involvement of RORs genes in the risk of developing BD. Investigation of the functional properties of genes in the circadian pathway may further enhance our understanding about the pathogenesis of bipolar illness.

Familiality and clinical outcomes of sleep disturbances in major depressive and bipolar disorders.

OBJECTIVE: Sleep disturbances are frequently observed in major depressive (MDD) and bipolar disorder (BD). This study reported sleep profiles of patients and their relatives versus controls, and examined the familiality of sleep features in mood disorder families. We also evaluated the influences of sleep disturbance on patients' quality of life (QOL), functional impairment, and suicidality. METHODS: We recruited 363 BD and 157 MDD patients, 521 first-degree relatives, and 235 healthy controls, which completed a diagnostic interview, Pittsburgh Sleep Quality Index (PSQI), and QOL questionnaire. The magnitude of heritability of sleep features was calculated and familiality was evaluated by mixed regression models and intraclass correlation coefficient (ICC). The associations between sleep problems and clinical outcomes were examined using multiple regression models. RESULTS: More than three-quarters of mildly-ill patients were classified as "poor sleepers". MDD patients had significantly worse sleep quality as compared to BD patients. Moderate but significant familial aggregation was observed in subjective sleep quality, sleep latency, disturbance, daytime dysfunction, and global score (ICC=0.10-0.21, P<.05). Significant heritability was found in sleep quality (0.45, P<.001) and sleep disturbance (0.23, P<.001). Patients with good sleep quality had better QOL and less functional impairment (P<.05) than poor sleepers. Poor sleep quality and nightmares further increased the risk for suicidal ideation (ORadj=2.8) and suicide attempts (ORadj=1.9-2.8). CONCLUSION: Subjectively measured sleep features demonstrated significant familiality. Poor sleep quality further impaired patients' daily function and QOL, in addition to increasing the risk of suicidality, and thus requires special attention in related clinical settings.

Relaxation of a field-unwound cholesteric liquid crystal.

We have numerically investigated the homogeneous-planar and homeotropic-planar transitions, respectively, in a planar-aligned cholesteric liquid crystal by using our multidimensional software based on the finite element method. When the unwinding field is turned off abruptly, the relaxation process of a field-unwound cholesteric liquid crystal is accompanied by an elastic-induced Helfrich deformation without introduction of defects, which will continuously convert into a stable planar texture with natural pitch and domain wall.