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Biochemistry, biology and carcinogenicity of tobacco-specific N-nitrosamines

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Distal influences are intermediate or indirect factors that may be more predictive

However, a significant question remains about whether these associations represent predisposing features for the risk of developing cigarette smoking or are consequences of cigarette smoking. Specifically, they looked over data on health behaviors, brain scans, and genetic risk factors, all drawn from the dataset known as the UK Biobank, and then performed statistical analysis to see if daily smoking led to decreased brain volume over time

N Engl J Med 370:60-68 Goodchild M, Nargis N, Tursan dEspaignet E, 2017