• 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, and George Davey Smith.
• MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK Rebecca.richmond@bristol.ac.uk.
• BMJ. 2019 Jun 26; 365: l2327.

ObjectiveTo examine whether sleep traits have a causal effect on risk of breast cancer.DesignMendelian randomisation study.SettingUK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.Participants156 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.ExposuresSelf 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 MeasureBreast cancer diagnosis.ResultsIn 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.ConclusionsFindings 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.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

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