How is "Ease of Awakening" encoded by the genome?
How easy is it for you to wake up in the morning? Awakening is a crucial event for humans, and has been reported to be associated with sleep-related disorders. Age may be one of the powerful factors which influence awakening. Recent studies have suggested that genetic variants may contribute to individual differences in ease of awakening.
In the area of sleep research, the relationship between sleep-related traits and health status has been a hot topic. It is well known that inadequate sleep duration and poor sleep quality has been reported to be fundamental risk factor for heart disease. In order to discover the genetic basis and causal relationship with cardiometabolic health, researchers performed multi-trait colocalization analyses of daytime napping loci across six self-reported sleep traits (daytime sleepiness, sleep duration, insomnia, snoring, chronotype, and ease of awakening) in the UK Biobank.
In the genome-wide association study (GWAS) for ease of awakening, the level of ease of awakening was measured by questionnaires which were answered by 4 point liker scale. They identified 33 shared signals between those sleep-related traits. As for ease of awakening, the most significant associations were observed for rs2653349 in the wake-promoting hypocretin receptor 2 (HCRTR2) gene. The A allele of this variant was also associated with more frequent daytime napping and morning preference. In addition, T allele of the rs9309116 in the prolyl endopeptidase like (PREPL) gene showed an increased in ease of getting up. The HCRTR2 gene has been reported to be an established drug targets for sleep disorders. They also examined if HCRTR2 (A allele of rs2653349) was associated with large GWAS cardiovascular phenotypes. This analysis revealed no associations of the variants with cardiovascular outcomes, but showed positive effects on systolic blood pressure. A hypothesis-free scan across 1402 ICD-code defined phenotypes in the UK Biobank was performed but found no variant- disease associations. Therefore, the present human genetic evidence does not support a net excess adverse cardiovascular risk from on-target inhibition of HCRTR2.
The finding in this study is consistent with previous studies and it is thus possible that orexin receptor agonism, a therapeutic strategy currently under investigation for narcolepsy, may have roles in the treatment of patients with more mild deficits in the arousal/wake drive system. Read more about the study here:
https://pubmed.ncbi.nlm.nih.gov/33568662/
Are you interested in learning more about your genetic tendency for ease of awakening? You can login to your Genomelink YOUR TRAITS to see this new genetic trait.
