Using Mendelian Randomisation to Establish the Causal Role of Cigarette Smoking in Anxiety and Depression

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Cigarette smokers typically have higher levels of anxiety and depression, while people with anxiety and depression are more likely to smoke. There are broadly two explanations for this: One is that cigarette smoking increases the risk of anxiety and depression, while the other is that people with anxiety and depression are more likely to smoke because it helps them to regulate their mood. This is an important question, not least because it may help to identify novel ways with which to treat depression (for example, by isolating some of the relevant chemicals within cigarette smoke). However, it is difficult to disentangle these possibilities because it is unethical to randomly assign some people to smoke and others not to. Other factors which influence both how likely you are to smoke, and how likely you are to be anxious or depressed, may also give the impression of a causal relationship when in fact there is none - a problem known as confounding.We know that genes may influence the likelihood of starting smoking, how much one smokes, and how easy it is to stop smoking. Recently, some specific genes which predict the likelihood of how much one smokes have been identified. The version of a gene which you have is an essentially random process which means that it is unrelated to other factors which might introduce confounding. This means that these genes can be used as "instrumental variants" which influence, for example, how much one smokes - people with one version may, on average, smoke slightly more than those with a different version in a way which is unrelated to other factors (such as income level, which is a common confounding factor). If these genes are also associated with the likelihood of anxiety and depression, in particular among smokers but not among non-smokers, this would provide evidence of a causal relationship between cigarette smoking and anxiety and depression.We propose to use existing data which has been collected on a large number of people about their smoking habits, anxiety and depression, as well as genetic data on genes which influence heaviness of smoking and the ability to stop smoking. This will provide very important insights into whether and how cigarette smoking is causally related to anxiety and depression, and potentially lead to the development of novel treatments for these very common and disabling mental health problems.