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Selection into shift work is influenced by educational attainment and body mass index: A Mendelian randomization study

By Iyas Daghlas, Rebecca C Richmond, Jacqueline M. Lane, Hassan S Dashti, Hanna M Ollila, Eva S. Schernhammer, George Davey Smith, Martin K Rutter, Richa Saxena, CĂ©line Vetter

Posted 13 Mar 2020
medRxiv DOI: 10.1101/2020.03.10.20032698

BackgroundShift work is associated with increased cardiometabolic disease risk, but whether this association is influenced by cardiometabolic risk factors driving selection into shift work is currently unclear. We addressed this question using Mendelian randomization (MR) in the UK Biobank. MethodsWe created genetic risk scores (GRS) associating with nine cardiometabolic risk factors (including education, body mass index [BMI], smoking, and alcohol consumption), and tested associations of each GRS with self-reported current frequency of shift work and night shift work amongst employed UKB participants of European ancestry (n=190,573). We used summary-level MR sensitivity analyses and multivariable MR to probe robustness of the identified effects, and tested whether effects were mediated through sleep timing preference. ResultsGenetically instrumented lower educational attainment and higher body mass index increased odds of reporting frequent shift work (odds ratio [OR] per 3.6 years [1-SD] decrease in educational attainment=2.40, 95% confidence interval [CI]=2.22-2.59, p=4.84 x 10-20; OR per 4.7kg/m2 [1-SD] increase in BMI=1.30, 95%CI=1.14-1.47, p=5.85 x 10-05). Results were unchanged in sensitivity analyses allowing for different assumptions regarding horizontal pleiotropy, and the effects of education and BMI were independent in multivariable MR. No causal effects were evident for the remaining factors, nor for any exposures on selection out of shift work. Sleep timing preference did not mediate any causal effects. ConclusionsEducational attainment and BMI may influence selection into shift work, which may have implications for epidemiologic associations of shift work with cardiometabolic disease. Key messagesO_LIAlthough it has been hypothesized that cardiometabolic risk factors and diseases may influence selection into shift work, little evidence for such an effect is currently available. C_LIO_LIUsing Mendelian randomization, we assessed whether cardiometabolic risk factors and diseases influenced selection into or out of shift work in the UK Biobank. C_LIO_LIOur results were consistent with a causal effect of both higher BMI and lower educational attainment on selection into current shift work, with stronger effects seen for shift work that is more frequent and includes more night shifts. C_LIO_LIUsing multivariable Mendelian randomization, we found that effects of higher BMI and lower education were independent. Sleep timing preference had a null effect on shift work selection and therefore did not mediate these effects. C_LIO_LISelection through education and BMI may bias the relationship of shift work with cardiometabolic disease. Social mechanisms underlying these effects warrant further investigation. C_LI

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