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

吸烟者通常有更高的焦虑和抑郁水平，而焦虑和抑郁的人更有可能吸烟。对此大致有两种解释：一种是吸烟会增加焦虑和抑郁的风险，另一种是焦虑和抑郁的人更有可能吸烟，因为吸烟有助于调节他们的情绪。这是一个重要的问题，尤其是因为它可能有助于确定治疗抑郁症的新方法(例如，通过分离香烟烟雾中的一些相关化学物质)。然而，很难理清这些可能性，因为随机分配一些人吸烟，另一些人不吸烟是不道德的。其他因素既影响你吸烟的可能性，也影响你焦虑或抑郁的可能性，也可能给人一种因果关系的印象，但实际上并不存在--这就是所谓的混淆问题。我们知道，基因可能会影响开始吸烟的可能性、吸烟量以及戒烟的难易程度。最近，一些特定的基因被识别出来，这些基因可以预测一个人吸烟的可能性。你拥有的基因版本本质上是一个随机过程，这意味着它与其他可能引入混杂的因素无关。这意味着，这些基因可以被用作影响吸烟量的“工具变量”--平均而言，一个基因的人可能比另一个基因版本的人吸烟略多一些，而这种方式与其他因素(如收入水平，这是一个常见的混杂因素)无关。如果这些基因也与焦虑和抑郁的可能性有关，特别是在吸烟者中，但在非吸烟者中，这将提供吸烟与焦虑和抑郁之间因果关系的证据。我们建议使用现有的数据，这些数据收集了大量关于他们的吸烟习惯、焦虑和抑郁的数据，以及影响吸烟严重程度和戒烟能力的基因的基因数据。这将为吸烟是否以及如何与焦虑和抑郁之间存在因果关系提供非常重要的见解，并可能导致开发针对这些非常常见和致残的心理健康问题的新疗法。

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.