0033 Genome-wide association analysis of composite sleep scores in 413,904 individuals

Abstract Introduction Recent genome-wide association studies (GWAS) of individual sleep traits have identified hundreds genetic loci, often implicating genes and biological pathways that are shared across phenotypes. Modeling multiple dimensions may allow identification common underlying mechanisms complement analyses traits. Moreover, construction novel health scores, accounting for correlations between traits, has the potential to enhance specificity power analyses. Methods We performed GWAS composite scores derived from five questions characterizing 413,904 individuals European ancestry UK Biobank. constructed an additive score (SS-add) as a sum up favorable self-reported behaviors (sleep duration 7-8 hours, early chronotype, few insomnia symptoms, no snoring, excessive daytime sleepiness) well principal component (SS-PC1 – SS-PC5) using SNP-level were complemented with follow-up analyses, including investigation pathway, tissue, cell-type enrichments, comprehensive correlation (381 representative phenotypes) bi-directional Mendelian randomization (MR) (40 selected phenotypes). Results Sleep SS-PC1 (interpretable longer without symptoms) SS-PC2 (healthy snoring or showed higher heritability (respectively 11.7% 9.3%) compared their primary SS-PC3 (loading strongly on chronotype) highest overall (15.3%). Accounting six GWAS, we 28 significant loci (p< 8.3e-9), 31 additional 5e-8), 341 previously reported 5e-8) by Associated mapped enriched in expression brain tissues, metabolic neuronal pathways. Numerous neurological, cardiometabolic other genetically correlated (104 with|rho_g|>0.3, p< 2e-5). MR associations 2e-4) pointed causes (BMI [SS-PC2/PC4], smoking [SS-add/PC1], lower socio-economic status [SS-add/PC5]) consequences (coronary heart disease pain [SS-PC1/5]) poor sleep. Conclusion Composite revealed related behaviors, helped clarify relationships neurological deserve further investigation. Support (if any) R01HL153814 (to H.W.), NHLBI R35HL135818 S.R.), 1R01HL146751 R.S.), UKB Application 6818.