refer to substance use, but also to factors such as cholesterol or metabolite levels or blood pressure, which are directly influenced by lifestyle choices. A failure to appreciate this point will hamper our ability to translate the results of GWAS into health benefits, by focusing attention on possible biological pathways when, in fact, the target for intervention could be a modifiable environmental or behavioural exposure. We also need to be cautious when using statistical adjustment to test whether a genetic variant operates entirely via the supposed intermediate behavioural pathway. Sometimes, the most parsimonious explanation (e.g., smoking causes lung cancer) is the best one.
