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.

Assessing the Relationship Between Gut Microbiota and Bone Mineral Density

“…Then, the approach has motivated several other applications, including polygenic Mendelian Randomization (Hung et al, 2014). For instance, PRS analysis has been successfully applied to multiple complex diseases, such as diabetes, sleep traits, and coronary heart disease (Kawai et al, 2017;Carter et al, 2019;Nazarzadeh et al, 2019;Richmond et al, 2019).…”

Changes In Self-Reported Sleep Duration With Age - A 36-Year Longitudinal Study Of Finnish Adults

“…Not until the last decades have we learned that poor sleep is not only comorbid with many disorders, but may also be a contributing causative factor, as shown in, for example, cardiovascular disease [1,[28][29][30]. Evidence for a causal role in breast cancer [31] and type 2 diabetes [32,33] is less convincing. Genetic analyses suggest shared genetic liability to sleep duration and a variety of other medically relevant traits and diseases [34], but the causal paths require more studies.…”

Genetics of the human circadian clock and sleep homeostat

“…There are higher rates of a wide range of disorders including psychological disorders, diabetes, neurological, gastrointestinal, and respiratory in definite evening types compared with definite morning types [25]. Morning preference appears to have a protective effect against breast cancer using a Mendelian randomization study model to investigate the impact of chronotype on breast cancer diagnosis in the UK Biobank [71]. Within diseases, such as bipolar and chronic migraine, evening type may impact frequency of episodes [72,73].…”