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Genetic determinants of daytime napping and effects on cardiometabolic health

2021; Nature Portfolio; Volume: 12; Issue: 1 Linguagem: Inglês

10.1038/s41467-020-20585-3

2041-1723

Hassan S. Dashti, Iyas Daghlas, Jacqueline M. Lane, Yunru Huang, Miriam S. Udler, Heming Wang, Hanna M. Ollila, Samuel E. Jones, Jaegil Kim, Andrew R. Wood, Michelle Agee, Adam Auton, Robert K. Bell, Katarzyna Bryc, Sarah Clark, Sarah L. Elson, Kipper Fletez‐Brant, Pierre Fontanillas, Nicholas A. Furlotte, Pooja Gandhi, Karl Heilbron, Barry Hicks, David A. Hinds, Karen E. Huber, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Keng‐Han Lin, Nadia K. Litterman, Marie K. Luff, Jennifer C. McCreight, Matthew H. McIntyre, Kimberly F. McManus, Joanna L. Mountain, Sahar V. Mozaffari, Priyanka Nandakumar, Elizabeth S. Noblin, Carrie A. M. Northover, Jared O’Connell, Aaron A. Petrakovitz, Steven J. Pitts, G. David Poznik, J. Fah Sathirapongsasuti, Anjali J. Shastri, Janie F. Shelton, Suyash Shringarpure, Chao Tian, Joyce Y. Tung, Robert J. Tunney, Vladimir Vacic, Xin Wang, Amir S. Zare, Michael N. Weedon, Stella Aslibekyan, Marta Garaulet, Richa Saxena,

Circadian rhythm and melatonin

Abstract 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.