Multi-ancestry genetic architecture of sleep duration and its relationship to other sleep and psychiatric phenotypes

Differences in sleep duration, quality, and timing are associated with variation in cognition, health outcomes, and quality of life. Genetic studies may help explain the underlying mechanisms of sleep and its relationships to other conditions. Our previous work highlighted risk loci associated with short (<6hrs) and long sleep (>9hrs), using data from the UK Biobank and the Million Veteran Program. We build on this work by conducting a genome wide association study (GWAS) and multi-ancestry meta-analysis of sleep duration as a quantitative trait. We used LD score regression (LDSC) to evaluate the correlation between sleep duration and other traits, and genomic structural equation modelling (genomicSEM) to consider the relationships between traits of interest. We identify 234 independent genome-wide significant loci for sleep duration, of which 143 are novel. The average impact of each risk variant amounts to approximately {+/-}0.86minutes (sd=0.19), with a sum total of {+/-} 220.5 minutes across all genome-wide significant loci. We support previous findings showing the most strongly associated gene is PAX8. Linkage disequilibrium score regression shows that the genetic architecture of sleep duration is largely distinct from other measures of sleep quality and sleep disorders. We see several examples of negative correlation between deleterious traits and the quantitative measure of sleep duration reported here, contrasting with positive associations with long and short sleep (e.g., depression, ADHD, cannabis use disorder, smoking). We derive genomic-SEM models that show short and long sleep load on separate factors, as does overall sleep duration loading alone. This is the largest available GWAS of sleep duration, and the first to extend analyses outside of European ancestry populations. We identify novel loci for sleep duration and provide insight to the shared and unique genetic architecture across multiple sleep and neuropsychiatric traits.