Forskning

January 17, 2018

Investigating causal association between use of nicotine, alcohol, caffeine, and cannabis: a two-sample bidirectional Mendelian randomization study

K J H Verweij et al, 2018. Investigating causal association between use of nicotine, alcohol, caffeine, and cannabis: a two-sample bidirectional Mendelian randomization study, Addiction, published online.

ABSTRACT:

BACKGROUND AND AIMS: Epidemiological studies consistently show co-occurrence of use of different addictive substances. Whether these associations are causal or due to overlapping underlying influences remains an important question in addiction research. Methodological advances have made it possible to use published genetic associations to infer causal relationships between phenotypes. In this exploratory study, we used Mendelian randomization (MR) to examine the causality of well-established associations between nicotine, alcohol, caffeine, and cannabis use.

METHODS: Two-sample MR was employed to estimate bi-directional causal effects between four addictive substances: nicotine (smoking initiation and cigarettes smoked per day), caffeine (cups of coffee per day), alcohol (units per week), and cannabis (initiation). Based on existing genome-wide association results we selected genetic variants associated with the exposure measure as an instrument to estimate causal effects. Where possible we applied sensitivity analyses (MR-Egger and weighted median) more robust to horizontal pleiotropy.

RESULTS: Most MR tests did not reveal causal associations. There was some weak evidence for a causal positive effect of genetically instrumented alcohol use on smoking initiation and of cigarettes per day on caffeine use, but these did not hold up with the sensitivity analyses. There was also some suggestive evidence for a positive effect of alcohol use on caffeine use (only with MR-Egger) and smoking initiation on cannabis initiation (only with weighted median). None of the suggestive causal associations survived corrections for multiple testing.

CONCLUSIONS: Two-sample Mendelian randomization analyses found little evidence for causal relationships between nicotine, alcohol, caffeine, and cannabis use.