Aims

To investigate the possible bidirectional association between smoking and caffeine consumption using Mendelian randomization.

Hypotheses

Coffee consumption and cigarette smoking are highly comorbid [1]. Observational studies suggest that coffee drinkers are more likely to be smokers than non-drinkers [1, 2], and also suggest a positive association between coffee consumption and cigarette consumption [3], and an inverse relationship between coffee consumption and smoking cessation [4].

However, the causal nature and direction of these effects are unknown and are difficult to infer from observational studies. Mendelian randomization methods minimise bias from confounding and remove the possibility of reverse causality [5].

Genetic variants for both smoking behaviour phenotypes and coffee consumption have been identified in genome-wide association studies [6, 7]. These can be used as instruments for measured coffee consumption and smoking behaviour in Mendelian randomization studies. Polygenic risk scores for these exposures can be generated from GWAS data to increase the power of Mendelian randomization analysis [8].

Polygenic risk scores for smoking behaviours and caffeine consumption will be generated from GWAS data for both the ALSPAC mothers and ALSPAC children. We will investigate the associations of genetic risk scores for smoking with caffeine consumption and the association of genetic risk scores for caffeine consumption with smoking. These analyses will be run in parallel with data from the Netherlands Twin Registry.