How is "Daytime Napping" encoded by the genome?
How often do you take naps during the day? In modern society, napping is encouraged in sleep-deprived populations, like night-shift workers and airline pilots, to acutely improve performance and alertness. Interestingly, naps, or short daytime sleep episodes, have a long history in the evolution of diverse diurnal species ranging from flies to mammals. Although napping appears to have an acute benefit on increased arousal in the setting of sleep deprivation, the long-term effects of habitual napping on chronic disease risk remain controversial.
Genetic variation constitutes an important contributor to interindividual differences in napping preference. One twin study estimated the heritability of self-reported napping and objective daytime sleep duration to be 65% and 61%, respectively, demonstrating heritability similar or evn more inherited than other sleep traits like nighttime sleep duration and timing. Indeed, up to seven genetic loci for daytime napping have been discovered in genome-wide association studies (GWAS) of self-reported napping or related accelerometer-derived sleep measures. Discovery of additional genetic loci may reveal biological pathways regulating sleep, elucidate genetic links with other sleep and metabolic traits, and clarify the potential causal effects of habitual napping on cardiometabolic disease. In order to discover the genetic basis and connection to cardiometabolic health, researchers performed a genome-wide association study of self-reported daytime napping using the largest discovery and replication sample sizes to date.
In this study, participants from the UK Biobank (UKB, n = 452,633) cohort were asked “Do you have a nap during the day?” with response options of “Never/rarely,” “Sometimes,” “Usually,” and “Prefer not to answer.” “Prefer not to answer” responses were set to missing. Participants further self-reported items such as demographic characteristics, anthropometric traits, sleep duration, chronotype, and overall health. After genotyping, 123 independent loci were identified to be associated with daytime napping in the UKB samples. Among these, 61 loci were successfully replicated in the 23andMe research cohort (n = 541,333). These loci include single nucleotide polymorphisms (SNPs) such as rs2653349 located near the HCRTR2 gene, rs12140153 near the PATJ gene, rs2250377 near the SHISA4 gene, rs174541 in the FADS2/FEN1 gene, rs11258652 in the FRMD4A gene, rs1001817 near the ECE2 gene, rs2769916 near the FAM155A gene, and rs6919087 near the MDGA1/ZFAND3 gene. The HCRTR2 gene has been investigated as a drug target for sleep disorders, and the PATJ gene has been suggested to be related with the hypersomnolence (hypersomnia) pathway. In addition, Mendelian randomization analysis showed potential causal links between more frequent daytime napping and higher blood pressure and waist circumference in this study.
A causal effect of more frequent napping with higher blood pressure is consistent with earlier epidemiologic findings between self-reported and measured daytime napping and hypertension. Mechanisms driving this relationship are unknown but may include detrimental effects of napping on nighttime sleep quality or chronic effects related to transient evening blood pressure surges following daytime napping. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/33568662/
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