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Using observational and genetic epidemiology to investigate the relationship between body mass index (BMI) and sleep duration

Garfield, Ana Victoria; (2018) Using observational and genetic epidemiology to investigate the relationship between body mass index (BMI) and sleep duration. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

Background: Evidence indicates that sleep duration predicts increases in BMI over time and thus, may lead to obesity. However, this relationship has not been explored to the same extent in the opposite direction and it is unclear whether there is a causal association between sleep duration and BMI, or vice versa. Bidirectional epidemiological methods can establish the direction of this association and genetic epidemiological methods may shed light on whether variation in BMI causes changes in sleep duration. // Methods: Observational, bidirectional analyses were carried out using the English Longitudinal Study of Ageing (ELSA) (Chapter 3) and a Norwegian community sample of children (Chapter 4). A genome-wide association study (GWAS) of sleep duration was then undertaken, with the aim of replicating previous, as well as identifying novel, loci (Chapter 5). A large-scale Mendelian randomization (MR) study was subsequently conducted, using genetic variants associated with BMI, to investigate the causal association between BMI and sleep duration in ~142,000 individuals; this was followed by polygenic risk score (PRS) analyses to investigate shared genetic aetiology between the two traits (Chapter 6). // Key findings: In older adults, higher BMI was associated with very small decreases in sleep duration, over 4-year follow-up; there was no association in the opposite direction from sleep duration to change in BMI. There was no association in either direction, between BMI and objective sleep duration in the sample of Norwegian children. The GWAS of sleep duration did not have sufficient power to replicate previous, or identify novel genetic variants for sleep duration, yet effects were consistent with those of previous GWA studies. The heritability of self-reported sleep duration was 7%, which is also in line with previous GWAS. MR findings suggested that it is uncertain whether a causal relationship exists between BMI and sleep duration and thus, triangulation of results is necessary. A polygenic risk score of BMI was negatively associated with sleep duration, showing some evidence of shared genetic aetiology; however, the variance explained was only 0.02%. // Conclusions: This thesis suggests that BMI and sleep duration are weakly associated and that using a combination of approaches is invaluable in helping us understand this relationship. In older adults, it appeared that prospectively, BMI predicted small changes in sleep duration, whilst in children there was no prospective relationship in either direction. Findings from the GWAS suggest that the heritability of self-reported sleep duration was low. Using MR it was not possible to firmly conclude whether BMI causes changes in sleep duration or not and therefore, more research is needed to determine this. Also, BMI and self-reported sleep duration do not appear to have much underlying common genetic aetiology.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Using observational and genetic epidemiology to investigate the relationship between body mass index (BMI) and sleep duration
Event: UCL
Open access status: An open access version is available from UCL Discovery
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
URI: https://discovery.ucl.ac.uk/id/eprint/10053572
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