Alzheimer’s – IEUREKA!

Deborah Lawlor, Professor of Epidemiology, Emma Anderson, MRC Research Fellow, Marcus Munafò, Professor of Experimental Psychology, Mark Gibson, PhD student, Rebecca Richmond, Vice Chancellor’s Research Fellow

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Association is not causation – are we fooled (confounded) when we see associations between sleep problems and disease?

Sleep is important for health. Observational studies show that people who report having sleep problems are more likely to be overweight, and have more health problems including heart disease, some cancers and mental health problems.

A major problem with conventional observational studies is that we cannot tell whether these associations are causal; does being overweight cause sleep problems, or do sleep problems cause people to become overweight? Alternatively, factors that influence how we sleep may also influence our health. For example, smoking might cause sleep problems as well as heart disease and so we are fooled (confounded) into thinking sleep problems cause heart disease when it is really all explained by smoking. In the green paper Advancing our Health: Prevention in the 2020s, the UK Government acknowledged that sleep has had little attention in policy, and that causality between sleep and health is likely to run in both directions.

But, how can we determine the direction of causality for sure? And, how do we make sure we are results are not confounded?

Randomly allocated genetic variation

Our genes are randomly allocated to us from our parents when we are conceived. They do not change across our lifespan, and cannot be changed by smoking, overweight or ill health.

Here at the MRC Integrative Epidemiology Unit we have developed a research method called Mendelian randomization, which uses this family-level random allocation of genes to explore causal effects. To find out more about Mendelian randomization take a look at this primer from the Director of the Unit (Prof George Davey Smith).

In the last two years, we and colleagues from the Universities of Manchester, Exeter and Harvard have identified large numbers of genetic variants that relate to different sleep characteristics. These include:

Insomnia symptoms
How long, on average, someone sleeps each night
Chronotype (whether someone is an ‘early bird’ or ‘lark’ and prefers mornings, or a ‘night owl’ and prefers evenings). Chronotype is thought to reflect variation in our body clock (known as circadian rhythms).

We can use these genetic variants in Mendelian randomization studies to get a better understanding of whether sleep characteristics affect health and disease.

What we did

In our initial studies we used Mendelian randomization to explore the effects of sleep duration, insomnia and chronotype on body mass index, coronary heart disease, mental health problems, Alzheimer’s disease, and breast cancer. We analysed whether the genetic traits that are related to sleep characteristics – rather than the sleep characteristics themselves – are associated with the health outcomes. We combined those results with the effect of the genetic variants on sleep traits which allows us to estimate a causal effect. Using genetic variants rather than participants’ reports of their sleep characteristics makes us much more certain that the effects we identify are not due to confounding or reverse causation.

What we found

Our results show a mixed picture; different sleep characteristics have varying effects on a range of health outcomes.

Insomnia appears to increase the risk of coronary heart disease and depression
Longer sleep duration may increase the risk of schizophrenia. And it also appears that liability to schizophrenia increases sleep duration.
Being a morning person appears to result in better mental health and protects against breast cancer, but does not influence body mass index or cardiometabolic health.
Breast cancer was not influenced by insomnia, but appeared to increase with longer sleep duration.
None of these classical sleep traits have any influence on Alzheimer’s disease, though we found some suggestive evidence that daytime napping might decreased its risk.
Insomnia may also increase smoking heaviness and reduce the likelihood of quitting.

What does this mean?

Having better research evidence about the effects of sleep traits on different health outcomes means that we can give better advice to people at risk of specific health problems. For example, developing effective programmes to alleviate insomnia may prevent coronary heart disease and depression in those at risk. It can also help reduce worry about sleep and health, by demonstrating that some associations that have been found in previous studies are not likely to reflect causality.

If you are worried about your own sleep, the NHS has some useful guidance and signposting to further support.

Want to find out more?

Contact the researchers

Deborah A Lawlor mailto:d.a.lawlor@bristol.ac.uk

Tag: Alzheimer’s

What can genetics tell us about how sleep affects our health?