Investigating the Relationship Between Smoking Behavior and Global Brain Volume
Yoonhoo Chang, Vera Thornton, Ariya Chaloemtoem, Andrey P. Anokhin, Janine Bijsterbosch, Ryan Bogdan, Dana B. Hancock, Eric O. Johnson, Laura J. Bierut
Abstract
Previous studies have shown that brain volume is negatively associated with cigarette smoking, but there is an ongoing debate whether smoking causes lowered brain volume or a lower brain volume is a risk factor for smoking. We address this debate through multiple methods that evaluate directionality: Bradford Hill’s Criteria that is commonly used to understand a causal relationship in epidemiological studies, and mediation analysis. In 32,094 participants of European descent from the UK Biobank dataset, we examined the relationship between a history of daily smoking and brain volumes, as well as association of genetic risk score to ever smoking with brain volume. A history of daily smoking is strongly associated with decreased brain volume, and a history of heavier smoking is associated with a greater decrease in brain volume. The strongest association was between total grey matter volume and a history of daily smoking (Effect size = -2964mm3 p-value = 2.04 x 10-16), and there was a dose response relationship with more pack years smoked associated with a greater decrease in brain volume. A polygenic risk score (PRS) for smoking initiation was strongly associated with a history of daily smoking (Effect size = 0.05, p-value = 4.20 ×10-84), yet only modestly associated with total grey matter volume (Effect size = - 424mm3, p-value = 0.01). Mediation analysis indicated that a history of daily smoking is a mediator between smoking initiation PRS and total grey matter volume. A history of daily smoking is strongly associated with a decreased total brain volume.