Genome-wide identification and functional validation of the WW domain containing oxidoreductase gene associated with...

Individual differences in sleep duration have been reported, and genetic components of sleep duration have been identified showing various heritability. To identify genetic variants that contribute to sleep duration, we conducted a human genome-wide identification on sleep duration and performed confirmatory experiments using a Drosophila model. Genome-wide association study in human was analyzed to determine the association of the genetic variants with self-aware sleep duration from two community-based cohort, Ansan (cohort 1, n = 4635) and Ansung (cohort 2, n = 4205), recruited from the Korean Genome and Epidemiology Study. Individual single nucleotide variants (rs16948804 and rs4887991) in the WW domain containing oxidoreductase (WWOX) gene were associated with self-aware sleep duration in human (p-values, 1.11 × 10^- 7 and 2.05 × 10^- 7, retrospectively). To examine the functional relevance of the WWOX gene identified in the genome-wide association study, we analyzed the sleep duration of Drosophila loss-of-function mutants. The deletion of Wwox in flies reduced sleep duration and quality with average bout length during daytime and increased night-time sleep duration (all of p-values < 0.01). Our findings suggested that WWOX expression is associated with sleep duration in both humans and Drosophila and genetic factors play a role in inter-individual variability in sleep characteristics.