B3952 - Orienting causal relationships between sleep and adiposity traits using genetic risk scores and mendelian randomisation - 20/12/2021

B number: 
Principal applicant name: 
Rebecca Richmond | University of Bristol (United Kingdom)
Miss Bryony Hayes
Title of project: 
Orienting causal relationships between sleep and adiposity traits using genetic risk scores and mendelian randomisation
Proposal summary: 

Poor sleep and obesity are problem that permeates though much of the UK population. Up to 67% of UK adults report disturbed sleep, 26 – 36% experience insomnia and 23% sleep for < 5 hrs per night1. Furthermore, a 2019 health survey for England found that 28.0% of adults in England are obese and a further 36.2% are overweight2. Similarly, obesity is a growing problem in the UK, amongst both children and young people. In 2019, a study by the National Child Measurement Programme (NCMP) found that by the age of five, 13.1% of children were overweight and 9.9% were obese. Between 2007 and 2019, the same study found that prevalence of obesity in year six children had increased from 17.5% to 21.0% 2.
Sleep traits such as chronotype (morning- or evening-preference), insomnia (difficulty initiating or maintaining sleep) and sleep duration (length of time spent sleeping) have previously been studied in relation to adiposity. In previous studies, increased odds of obesity has been associated with evening-preference chronotype4, occurrence of insomnia symptoms 5, and both short (<6h) and long (>9h) sleep duration5. Many studies have also found that individuals involved in night shift work are more likely to become overweight or obese6,7. In addition, associations have been found between increased obesity and both sleep apnoea8 and restless leg syndrome9, both of which may result in poor quality sleep10,11. However, it is often difficult to determine causal relationships and direction of effects in many of these studies, given the observational and often cross-sectional nature of the data.
We have recently performed preliminary Mendelian randomization to establish direction of effects between adiposity- and sleep-traits using summary data from genome-wide associations studies. We wish to follow up these findings using data from the Avon Longitudinal Study of Parents and Children (ALSPAC).
1. Aviva. Aviva health check UK report. (2016).
2. Baker, C. Inside: 1. Obesity in adults, England 2. Obesity in children. 3336, (2021).
3. Cole, T. J., Freeman, J. V. & Preece, M. A. British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Stat. Med. 17, 407–429 (1998).
4. Sun, X., Gustat, J., Bertisch, S. M., Redline, S. & Bazzano, L. The association between sleep chronotype and obesity among black and white participants of the Bogalusa Heart Study. Chronobiol. Int. 37, 123–134 (2020).
5. Cai, G.-H. et al. Insomnia symptoms and sleep duration and their combined effects in relation to associations with obesity and central obesity. Sleep Med. 46, 81–87 (2018).
6. Liu, Q. et al. Is shift work associated with a higher risk of overweight or obesity? A systematic review of observational studies with meta-analysis. Int. J. Epidemiol. 47, 1956–1971 (2018).
7. Brum, M. C. B. et al. Night shift work, short sleep and obesity. Diabetol. Metab. Syndr. 12, 13 (2020).
8. Romero-Corral, A., Caples, S. M., Lopez-Jimenez, F. & Somers, V. K. Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest 137, 711–719 (2010).
9. Gao, X., Schwarzschild, M. A., Wang, H. & Ascherio, A. Obesity and restless legs syndrome in men and women. Neurology 72, 1255–1261 (2009).
10. Bogan, R. K. Effects of restless legs syndrome (RLS) on sleep. Neuropsychiatr. Dis. Treat. 2, 513–519 (2006).
11. Miyahara, L. K. et al. Evaluation of sleep quality and risk of obstructive sleep apnea in patients referred for aesthetic rhinoplasty. Sleep Sci. (Sao Paulo, Brazil) 12, 126–131 (2019).

Impact of research: 
A better understanding of the causal direction between sleep traits and adiposity may be used to inform futures studies that explore the causal pathways between adiposity, sleep and health outcomes such as breast cancer, and may also be used to inform patient-based intervention studies.
Date proposal received: 
Wednesday, 15 December, 2021
Date proposal approved: 
Monday, 20 December, 2021
Genetic epidemiology (including association studies and mendelian randomisation), Obesity, Sleep traits such as chronotype, insomnia, sleep duration, napping during the day, daytime dozing, ease of getting up in the morning, GWAS, Statistical methods, Genetic risk scores, observational analyses, longitudinal analyses, BMI, Genetic epidemiology, Genetics, Genome wide association study, Mendelian randomisation, Methods - e.g. cross cohort analysis, data mining, mendelian randomisation, etc., Statistical methods