No evidence linking sleep traits with white blood cell counts: Multivariable-adjusted and Mendelian randomization analyses

Background: Disturbances in habitual sleep have been associated with multiple age-associated diseases. However, the biological mechanisms underpinning these associations remain largely unclear. We assessed the possible involvement of the circulating immune system by determining the associations between sleep traits and white blood cell counts using multivariable-adjusted linear regression and Mendelian randomization. Methods: Cross-sectional multivariable-adjusted linear regression analyses were done using participants within the normal range of total white blood cell counts (>4.5 x 10(9) and <11.0 x 10(9)/mu L) from UK Biobank. For the sleep traits, we examined (short and long) sleep duration, chronotype, insomnia symptoms and daytime dozing. Two-sample Mendelian randomization analyses were done using instruments for sleep traits derived from European-ancestry participants from UK Biobank (over 410,000 participants) and using SNP-outcome data derived from European-ancestry participants from the Blood Cell Consortium (N = 563,946) to which no data from UK Biobank contributed. Results: Using data from 357,656 participants (mean [standard deviation] age: 56.5 [8.1] years, and 44.4% men), we did not find evidence that disturbances in any of the studied sleep traits were associated with differences in blood cell counts (total, lymphocytes, neutrophiles, eosinophiles and basophiles). Also, we did not find associations between disturbances in any of the studied sleep traits and white blood cell counts using Mendelian Randomization. Conclusion: Based on the results from two different methodologies, disturbances in habitual sleep are unlikely to cause changes in blood cell counts and thereby differences in blood cell counts are unlikely to be underlying the observed sleep-disease associations.