Work

Investigating causal relationship between smoking behavior and global brain volume

Year: 2023

Type: preprint

Abstract: Background 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 causality: Bradford Hill’s Criteria to understand a causal relationship in epidemiological studies, mediation analysis, and Mendelian Randomization. Methods In 28,404 participants of European descent from the UK Biobank dataset, we examined relationships between a history of daily smoking and brain imaging phenotypes as well as associations of genetic predisposition to smoking initiation with brain volume. Results 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 (p-value = 8.28 × 10 −33 ), 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 (p-value = 4.09 ×10 −72 ), yet only modestly associated with total grey matter volume (p-value = 0.02). Mediation analysis indicated that a history of daily smoking is a mediator between smoking initiation PRS and total grey matter volume. Mendelian Randomization showed a causal effect of daily smoking on total grey matter volume (p-value = 0.022). Conclusions These converging findings strongly support the hypothesis that smoking causes decreased brain volume.

Source: medRxiv

DOI: 10.1101/2023.04.25.23288931