Genetic determinants of daytime napping and effects on cardiometabolic health.

1. Nat Commun. 2021 Feb 10;12(1):900. doi: 10.1038/s41467-020-20585-3.

Genetic determinants of daytime napping and effects on cardiometabolic health.

Dashti HS(#)(1)(2)(3), Daghlas I(#)(1)(2), Lane JM(1)(2)(3), Huang Y(4), Udler MS(1)(2)(5)(6), Wang H(2)(7), Ollila HM(1)(2)(8)(9), Jones SE(8)(10), Kim J(11), Wood AR(10); 23andMe Research Team; Weedon MN(10), Aslibekyan S(4), Garaulet M(12)(13)(14), Saxena R(15)(16)(17).

Collaborators: Agee M, Auton A, Bell RK, Bryc K, Clark SK, Elson SL, Fletez-Brant K, Fontanillas P, Furlotte NA, Gandhi PM, Heilbron K, Hicks B, Hinds DA, Huber KE, Jewett EM, Jiang Y, Kleinman A, Lin KH, Litterman NK, Luff MK, McCreight JC, McIntyre MH, McManus KF, Mountain JL, Mozaffari SV, Nandakumar P, Noblin ES, Northover CAM, O’Connell J, Petrakovitz AA, Pitts SJ, Poznik GD, Sathirapongsasuti JF, Shastri AJ, Shelton JF, Shringarpure S, Tian C, Tung JY, Tunney RJ, Vacic V, Wang X, Zare AS.

Author information: (1)Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (2)Broad Institute, Cambridge, MA, USA. (3)Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. (4)23andMe, Inc., Sunnyvale, CA, USA. (5)Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. (6)Department of Medicine, Harvard Medical School, Boston, MA, USA. (7)Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. (8)Institute for Molecular Medicine FIMM, HiLIFE, University of Helsinki, Helsinki, Finland. (9)Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. (10)Genetics of Complex Traits, University of Exeter Medical School, Exeter, UK. (11)GlaxoSmithKline, Waltham, MA, USA. (12)Division of Sleep and Circadian Disorders, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA. garaulet@um.es. (13)Department of Physiology, University of Murcia, Murcia, Spain. garaulet@um.es. (14)IMIB-Arrixaca, Murcia, Spain. garaulet@um.es. (15)Center for Genomic Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rsaxena@mgh.harvard.edu. (16)Broad Institute, Cambridge, MA, USA. rsaxena@mgh.harvard.edu. (17)Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. rsaxena@mgh.harvard.edu. (#)Contributed equally

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.

DOI: 10.1038/s41467-020-20585-3 PMCID: PMC7876146 PMID: 33568662 [Indexed for MEDLINE]

Conflict of interest statement: Y.H., S.A., and members of the 23andMe Research Team are employed by and hold stock or stock options in 23andMe, Inc. All remaining authors declare no competing interests.