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Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation 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.

SUBMITTER: Richmond RC

PROVIDER: S-EPMC6592406 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Richmond Rebecca C RC Anderson Emma L EL Dashti Hassan S HS Jones Samuel E SE Lane Jacqueline M JM Strand Linn Beate LB Brumpton Ben B Rutter Martin K MK Wood Andrew R AR Straif Kurt K Relton Caroline L CL Munafò Marcus M Frayling Timothy M TM Martin Richard M RM Saxena Richa R Weedon Michael N MN Lawlor Debbie A DA Smith George Davey GD

BMJ (Clinical research ed.) 20190626

<h4>Objective</h4>To examine whether sleep traits have a causal effect on risk of breast cancer.<h4>Design</h4>Mendelian randomisation study.<h4>Setting</h4>UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.<h4>Participants</h4>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 ...[more]

PMID: 31243001

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Project description:ObjectiveExtensive literature put forward the link between sleep and type 2 diabetes mellitus (T2DM), however, little is known about the underlying causality of the associations. Here we aim to assess the causal relationships between five major sleep-related traits and T2DM.Design setting and participantsTwo-sample Mendelian randomization (MR) was utilized to investigate the potential causal relations. Independent genetic variants associated with five sleep-related phenotypes-insomnia, sleep duration, short sleep duration, long sleep duration, and morningness-were chosen as instrumental variables to estimate the causal associations with T2DM. Summary statistics were acquired from the genome-wide association studies of UK Biobank and 23andMe (for sleep-related measures), the DIAbetes Genetics Replication And Meta-analysis and the FinnGen (for T2DM).Main methodsIndividual Cochran's Q statistic was applied to remove the pleiotropic instruments, global Q statistics and MR-Egger regression were adopted to test for the global heterogeneity and horizontal pleiotropy of the screened instruments, respectively. Two T2DM cohorts were selected to analyze their associations with sleep traits. A modified inverse variance weighted (IVW) estimate was performed to combine the ratio estimators from each instrument and acquire the causal estimate, alternative methods including IVW with first-order weights, simple and weighted median estimations, and MR-Egger regression were conducted as sensitivity analyses, to ensure the robustness and solidity of the findings.ResultsTwo-sample MR supported findings for an adverse effect of genetically predicted insomnia on T2DM risk (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.09-1.19, p = 1.29E-08) at the Bonferroni-adjusted level of significance (p < 0.005). We further investigated the causal role of T2DM on insomnia but obtained a non-significant estimation. There was also little evidence for the causal effect of other sleep-related measures on T2DM. Results were largely consistent when leveraging two different T2DM cohorts, and were robust among various sensitivity analyses.ConclusionFindings provide significant evidence for an adverse effect of insomnia on T2DM risk. The study extends fundamental knowledge to further understanding of the pathophysiological mechanisms of T2DM, and points out the non-negligible role of insomnia on epidemiologic intervention and clinical therapeutics of T2DM.

Dataset Information

Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

Publications

Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study.

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