Genetic determinants of daytime napping and effects on cardiometabolic health

Abstract

This is the final version. Available from Nature Research via the DOI in this record. ; Summary GWAS statistics are publicly available at The Sleep Disorder Knowledge Portal webpage: http://sleepdisordergenetics.org/. ; Daytime napping is a common, heritable behavior, but its genetic basis and causal relationship with cardiometabolic health remain unclear. Here, we perform a genome-wide association study of self-reported daytime napping in the UK Biobank (n = 452,633) and identify 123 loci of which 61 replicate in the 23andMe research cohort (n = 541,333). Findings include missense variants in established drug targets for sleep disorders (HCRTR1, HCRTR2), genes with roles in arousal (TRPC6, PNOC), and genes suggesting an obesity-hypersomnolence pathway (PNOC, PATJ). Association signals are concordant with accelerometer-measured daytime inactivity duration and 33 loci colocalize with loci for other sleep phenotypes. Cluster analysis identifies three distinct clusters of nap-promoting mechanisms with heterogeneous associations with cardiometabolic outcomes. Mendelian randomization shows potential causal links between more frequent daytime napping and higher blood pressure and waist circumference. ; National Institute of Health ; National Institute of Health ; National Institute of Health ; National Institute of Health ; National Institute of Health ; MGH Research Scholar Fund, Academy of Finland ; Medical Research Council ; Spanish Government of Investigation, Development and Innovation ; Seneca Foundation ; NIDDK ; Instrumentarium Science Foundation ; Yrjö Jahnsson Foundation