F75. exploring the role of nicotine and smoking in sleep behaviours: a multivariable mendelian randomisation study

Further investigation is warranted to understand the potential role of nicotine on sleep, considering the negative health effects of both sleep disturbances and smoking and the popularity of alternative nicotine product use to stop smoking. This study aimed to examine the direct effect of nicotine on sleep behaviours while accounting for non-nicotine constituents of tobacco smoke. We conducted a two-sample multivariable Mendelian Randomisation study using genetic proxies for nicotine metabolite ratio (NMR) (N SNP = 6) and cigarettes per day (CPD) (N SNP = 53) and six sleep outcomes, stratified by smoking status in ∼500,000 individuals in the UK Biobank. We found evidence that increased NMR decreases the likelihood of being an evening person when accounting for CPD in current (β= -0.04, 95%CI= -0.06, -0.02, P= < 0.001) and ever smokers (β= -0.03 95%CI= -0.04, -0.01, P= 0.003). We also observed evidence that increased NMR increases the likelihood of getting up in the morning in current smokers (β= 0.02, 95% CI= 0.01, 0.04, P = 0.015). We found evidence that increased NMR increases the likelihood of daytime napping in current smokers (β= 0.02, CI= 0.002, 0.03, P= 0.029), and evidence that increased NMR increases the likelihood of daytime sleepiness in current smokers (β= 0.01, 95%CI= -0.001, 0.02, P= 0.075). Decreased NMR (suggesting increased nicotine exposure per cigarette smoked) may prevent napping and sleepiness in the day while keeping smokers alert during the evening. Our findings suggesting that nicotine affects sleep even without exposure to other non-nicotine constituents of tobacco smoke.