Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study
Year: 2019
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: To examine whether sleep traits have a causal effect on risk of breast cancer. DESIGN: Mendelian randomisation study. SETTING: UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study. PARTICIPANTS: 156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis. EXPOSURES: Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits. MAIN OUTCOME MEASURE: Breast cancer diagnosis. RESULTS: In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy. CONCLUSIONS: Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.
Source: BMJ
DOI: 10.1136/bmj.l2327
Authors: Rebecca C Richmond, Emma L Anderson, Hassan S Dashti, Samuel E Jones, Jacqueline M Lane, Linn Beate Strand, Ben Brumpton, Martin K Rutter, Andrew R Wood, Kurt Straif, Caroline L Relton, Marcus Munafò, Timothy M Frayling, Richard M Martin, Richa Saxena, Michael N Weedon, Debbie A Lawlor, George Davey Smith
Institutions: University of Bristol, MRC Integrative Epidemiology Unit, Broad Institute, Harvard University, Massachusetts General Hospital, University of Exeter, Norwegian University of Science and Technology, St Olav's University Hospital, Manchester Academic Health Science Centre, University of Manchester, Manchester University NHS Foundation Trust, Centre international de recherche sur le cancer, University Hospitals Bristol NHS Foundation Trust, National Institute for Health and Care Research, NIHR Bristol Biomedical Research Centre, Brigham and Women's Hospital
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,732
Awards: Reproductive and cardio-metabolic health, The causes of hyperglycaemia in the face of rising obesity, Identifying non-coding mutations in early-onset diabetes, The genetics of sleep patterns and their relationship to obesity and Type 2 diabetes, UK Biobank (core renewal), Life course aetiology of dementia and cognitive decline: improving causal inference, Causes, Consequences and Modification of Health Behaviour, Epigenetic Epidemiology, Mendelian randomization to hypothesis-free causal inference, G76752795, Pleiotropy robust Mendelian randomization, Epigenetics: Environment, Embodiment and Equality (E4)
OpenAlex ID: W2953389908