An association study in the Taiwan Biobank reveals RORA as a novel locus for sleep duration in the Taiwanese Population

Background: Sleep is a key factor for health-related quality of life since sleep disturbances are a significant and common problem for patients with various human diseases such as psychiatric disorders. While single nucleotide polymorphisms (SNPs) in circadian clock genes have been indicated to be associated with sleep duration, most of the association studies have been investigated in populations with European ancestry. It is believed that no studies have been conducted to investigate a link between sleep duration and the circadian clock genes RORA and RORB, which play a key role, with NR1D1, in an additional feedback loop for the circadian rhythm machinery. Methods: In this study, we assessed the relationships between sleep duration and SNPs in the circadian clock genes NR1D1, RORA, and RORB in the Taiwan Biobank with a sample of 10,112 Taiwanese subjects. Results: From our data, we revealed a novel significant association in sleep duration with the rs75981965 SNP (P = 9.93 × 10?5) in the RORA gene that has not been previously identified. The association of sleep duration with this SNP remained significant after performing Bonferroni correction. RORA is a potential candidate for sleep duration as RORA has been suggested to play a key role in the regulation of sleep disorders. Additionally, we pinpointed the effects of interactions between RORA rs75981965 and environmental factors such as tea consumption (P = 0.0015), coffee consumption (P = 0.0029), physical activity (P = 0.011), alcohol consumption (P = 0.0146), and smoking (P = 0.0223) in influencing sleep duration. We also found interactions between RORA and NR1D1 (P = 0.0023) as well as between RORA and RORB (P = 0.0061) in affecting sleep duration. Conclusions: Our results indicate that the circadian clock gene RORA may contribute to sleep duration independently as well as through gene-gene and gene-environment interactions in the Taiwanese population. ? 2020 Elsevier B.V.