Alcohol use and smoking are common substance-use behaviors with well-established negative health effects, including decreased brain health. We examined whether alcohol use and smoking were associated with the same neuroimaging-derived brain measures. We further explored whether the effects of alcohol use and smoking on the brain were additive or interactive. We leveraged a cohort of 36,309 participants with neuroimaging data from the UK Biobank. We used linear regression to determine the association between 354 neuroimaging-derived brain measures and alcohol use defined as drinks per week, pack years of smoking, and drinks per week x pack years smoking interaction. To assess whether the brain associations with alcohol are broadly similar or different from the associations with smoking, we calculated the correlation between z-scores of association for drinks per week and pack years smoking. Results indicated overall moderate positive correlation in the associations across measures representing brain structure, magnetic susceptibility, and white matter tract microstructure, indicating greater similarity than difference in the brain measures associated with alcohol use and smoking. The only evidence of an interaction between drinks per week and pack years smoking was seen in measures representing magnetic susceptibility in subcortical structures. The effects of alcohol use and smoking on brain health appeared to be additive rather than multiplicative for all other brain measures studied. 97% (224/230) of associations with alcohol and 100% (167/167) of the associations with smoking that surpassed a p value threshold are in a direction that can be interpreted to reflect reduced brain health. Our results underscore the similarity of the adverse associations between use of these substances and neuroimaging derived brain measures.

LJB is listed as an inventor on Issued U.S. Patent 8,080,371, "Markers for Addiction," which covers the use of certain single nucleotide polymorphisms in determining the diagnosis, prognosis, and treatment of addiction. All other authors declare no competing interests.

AC, APA, LJB, SMH, and YC were supported by the National Institutes of Health (NIH) National Institute on Alcohol Abuse and Alcoholism (NIAAA) grant number U10AA008401 Collaborative Study on the Genetics of Alcoholism. JB is funded by the National Institute of Mental Health (NIMH) grants R01MH128286 and R01MH132962. DBH, EOJ, JDW, and LJB are funded by NIAAA grant number R01AA027049 Multi 'Omics Integration and Neurobiological Signatures of Alcohol Use Disorder. VT is additionally funded by Washington University Institute of Clinical and Translational Sciences grant number TL1TR002344. APA is additionally funded by NIH grants R01AA025646 and R01DA058114.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study uses data from the UK Biobank (UKB). The National Health Service North West Centre for Research Ethics Committee granted ethical approval for the UKB (Ref: 11/NW/0382). All participants provided informed consent per UKB procedures. Analyses were conducted under UKB Resource Application Number 48123.

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UK Biobank data used in this study are available folllowing application to the UKB.