Make a YouTube video on how you wake up at 5 am and all the positive impacts it can have on your life and you are guaranteed to get views. Many of the current videos have millions of hits. Did you know Mark Wahlberg wakes up at 2.30 am*!? Now, whilst I am not denying any of the claims made in these videos, having personally tried and tested it (the 5 am, not the 2.30 am), this early-waking routine will not work for everyone. Why not? We all have different propensities to fall asleep at a particular time within the 24-hour day and since we all should try to sleep ~7-9 hours this will heavily dictate when we would naturally wake up. How our propensities to sleep align with the day is referred to as our chronotype. Three key factors influence your chronotype; age, genetics and light. Or four, if you include gender, but that kinda comes under genetics.
So, our chronotypes will naturally change as we age, but why, and what genes are influencing our chronotypes? Whilst chronotypes have been well described, much less is known about the genetic mechanisms underpinning them. As circadian disruption such as via shift work is associated with increased risk of cancer, type 2 diabetes and depression, understanding what influences our clock may uncover strategies to better adjust and manage them to suit the differing lifestyles of the modern world. With a recent Nature paper by Jones et al. 1 identifying some genes through a large-scale GWAS, are we closer to understanding molecular basis of chronotypes?
* 13 M views for Mark Wahlberg’s wake-up routine, although James Corden personally makes this video…! https://www.youtube.com/watch?v=lzQyH-nX0u0&t=35s
What genes are associated with chronotype?
Jones’s group compiled data from previous genome-wide association studies (GWAS) where participants had self-identified their chronotype. The team identified 327 novel loci associated with a morning-chronotype bringing the total up to 351.
[ A refresher on GWAS: GWAS are used to identify gene loci associated with a trait. In this case the trait would be a “morning person”. To identify loci, genetic variants such as single nucleotide polymorphisms (SNPs) are analysed to see if certain variants appear more frequently in people with the trait than expected. The beauty of GWAS are that they are hypothesis free, but the key word to highlight in GWAS is association. Association of a loci with a trait doesn’t mean causation, but it nonetheless identifies loci that could be further studied. ]
Strongly associated gene loci were within the “core clock” genes such as the three PER genes and CRY1 (I have briefly introduced the circadian clock before –> https://asheekeyscienceblog.com/2018/12/31/mtorc-ing-about-circadian-rhythms-at-the-start-of-a-new-year-a-cytoplasmic-role-for-per2/ ).
In addition to an enrichment in circadian rhythm genes, genes involved in brain development and neurogenesis were strongly associated. Tissues enriched with these genes included all types of brain tissue and retinal tissue – since light is a strong zeitgeber of the circadian rhythm and light is detected by retinal cells, this tissue enrichment and the genes identified all seem very plausible. Another gene identified was FTO, involved in appetite regulation – since food also implicates entrainment of the circadian rhythm it seems that genetic variants that alter the timing of clock modulation subsequently influence chronotype. Nonetheless, to determine if any of these gene enrichments are actually causal for chronotype, individual in depth analyses will be required.
Disease associations stronger with circadian disruption than chronotypes
No associations with BMI, type 2 diabetes and insulin levels were seen with being a morning person, which conflicts with reported observational associations. The authors suggests that instead, chronotype dissonance (when you go against your chronotype e.g a late-morning person who has to wake early for work) may be a more important factor. Conversely, a positive genetic association between morningness and well-being was identified.
But if chronotype has a genetic underpinning, why does it change with age?
Chronotype changes with age
Data collected so far shows that chronotype gets later during adolescent and then advances back to being earlier again after entering the 20s (Figure 1).
Figure 1: Chronotype shifts during ageing. Graph modified from results in ref 2
Just like why different cell types with the same DNA are different, which genes our expressed, by how much and when will vary depending on age (and gender). It is currently thought that the onset of puberty is predominantly responsible for the change towards evening-ness in adolescents 3. Hormonal differences, such as testosterone, are thought to explain the gender differences seen – male students with higher testosterone levels are positively correlated with evening-ness 4. Results like these are urging many to argue for later school start times. These differences will again become clearer once the general mechanisms of chronotype are further explored.
Lark or an owl – how do I tell?
Without doing any genetic testing, age is a good indicator to use, but otherwise you are. Do you feel sluggish when you wake before 6/always do your best work in the evening? Whilst chronotype preference may seem trivial, it can have a huge impact on your life and risk of metabolic diseases. Adjusting your work/school schedule to suit your chronotype may be out of your hands, but for now appreciating and embracing your chronotype is the best you can do to keep your circadian rhythm most optimal and to avoid diseases that are associated with circadian disruption.
Life on Mars?
“Will my circadian rhythm be okay?” may not be on the top of your list of questions if you were suddenly going to move to Mars, but since a “Mars day” is 37 minutes longer than an “Earth day” this could really mess with your rhythm. So, although morning people may have better well-being, those with later chronotypes may be better suited to living on Mars. Okay, a strange way to end, but just goes to show the diverse ways in which chronotypes can affect our lives.
- Jones, S. E. et al. Genome-wide association analyses of chronotype in 697,828 individuals provides insights into circadian rhythms. Nat. Commun. (2019). doi:10.1038/s41467-018-08259-7
- Fischer, D., Lombardi, D. A., Marucci-Wellman, H. & Roenneberg, T. Chronotypes in the US – Influence of age and sex. PLoS One (2017). doi:10.1371/journal.pone.0178782
- Randler, C., Faßl, C. & Kalb, N. From Lark to Owl: Developmental changes in morningness-eveningness from new-borns to early adulthood. Sci. Rep. (2017). doi:10.1038/srep45874
- Randler, C. et al. Chronotype but not sleep length is related to salivary testosterone in young adult men. Psychoneuroendocrinology (2012). doi:10.1016/j.psyneuen.2012.02.008