Evidence for genetic correlations and bidirectional, causal effects between smoking and sleep behaviours

Abstract

Introduction: Cigarette smokers are at increased risk of poor sleep behaviours. However, it is largely unknown whether these associations are due to shared (genetic) risk factors and/or causal effects (which may be bi-directional). Methods: We obtained summary-level data of genome-wide association studies of smoking (smoking initiation (n=74,035), cigarettes per day (n=38,181) and smoking cessation (n=41,278)) and sleep behaviours (sleep duration and chronotype, or 'morningness') (n=128,266) and insomnia (n=113,006)). Using LD score regression, we calculated genetic correlations between smoking and sleep behaviours. To investigate causal effects, we employed Mendelian randomization (MR), both with summary-level data and individual level data (n=333,581 UK Biobank participants). For MR with summary-level data, individual genetic variants were combined with inverse-variance weighted meta-analysis, weighted median regression and MR Egger regression methods. Results: We found positive genetic correlations between insomnia and smoking initiation (rg=0.27, 95% CI 0.06 to 0.49) and insomnia and cigarettes per day (rg=0.15, 0.01 to 0.28), and negative genetic correlations between sleep duration and smoking initiation (rg=-0.14, -0.26 to -0.01) and chronotype and smoking cessation (rg=-0.18, -0.31 to -0.06). MR analyses provided strong evidence that smoking more cigarettes per day causally decreases the odds of being a morning person, and weak evidence that insomnia causally increases smoking heaviness and decreases smoking cessation odds. Conclusions: Smoking and sleep behaviours show moderate genetic correlation. Heavier smoking seems to causally affect circadian rhythm and there is some indication that insomnia increases smoking heaviness and hampers cessation. Our findings point to sleep as a potentially interesting smoking treatment target.

Causal Relationship Between Sleep Traits and Risk of Systemic Lupus Erythematosus: A Two-Sample Mendelian Randomization Study

“…The SNPs used for analysis were manually searched in the PhenoScanner database, and five traits that may develop potential pleiotropy, "alcohol intake frequency", "averageweekly beer plus cider intake", "current tobacco smoking", "ever smoked" and "past smoked smoking", were detected. Because the two characteristics of smoking and alcohol consumption have already been shown to be common predictors of sleep and SLE in previous studies (49)(50)(51)(52) and they are not intermediate variables in the causation of sleep and SLE. As a result, in this study, smoking and alcohol consumption were employed as confounders for exposure outcomes.…”

MR-pheWAS with stratification and interaction: Searching for the causal effects of smoking heaviness identified an effect on facial aging

“…Our results confirmed several established or previously reported causal effects of smoking heaviness. For example, our findings suggested higher smoking heaviness was associated with worse lung function (FIDs={3063, 20150, 20151}) (23), higher resting heart rate (FID=102) (24,25), higher risk of chronic obstructive pulmonary disease (FID=22130) (23) and lung cancer (FID=40001 value C349) (26), and lower odds of being a morning person (FID=1180) (27).…”

MR-pheWAS with stratification and interaction: Searching for the causal effects of smoking heaviness identified an effect on facial aging

“…Our results confirmed several established or previously reported causal effects of smoking heaviness. For example, our findings suggested higher smoking heaviness was associated with worse lung function (FIDs = {3063, 20150, 20154}) [25], higher risk of chronic obstructive pulmonary disease (FID = 22130) [25] and skin cancer (FID = 40011 value 8071) [26], and lower odds of being a morning person (FID = 1180) [27].…”