• Sandra Sanchez-Roige, Nancy J Cox, Eric O Johnson, Dana B Hancock, and Lea K Davis.
• Department of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address: sanchezroige@ucsd.edu.
• Drug Alcohol Depend. 2021 Apr 1; 221: 108612.

PurposeTo investigate the role of consumption phenotypes as genetic proxies for alcohol misuse and nicotine dependence.MethodsWe leveraged GWAS data from well-powered studies of consumption, alcohol misuse, and nicotine dependence phenotypes measured in individuals of European ancestry from the UK Biobank (UKB) and other population-based cohorts (largest total N = 263,954), and performed genetic correlations within a medical-center cohort, BioVU (N = 66,915). For alcohol, we used quantitative measures of consumption and misuse via AUDIT from UKB. For smoking, we used cigarettes per day from UKB and non-UKB cohorts comprising the GSCAN consortium, and nicotine dependence via ICD codes from UKB and Fagerström Test for Nicotine Dependence from non-UKB cohorts.ResultsIn a large phenome-wide association study, we show that smoking consumption and dependence phenotypes show similar strongly negatively associations with a plethora of diseases, whereas alcohol consumption shows patterns of genetic association that diverge from those of alcohol misuse.ConclusionsOur study suggests that cigarette smoking consumption, which can be easily measured in the general population, may be good a genetic proxy for nicotine dependence, whereas alcohol consumption is not a direct genetic proxy of alcohol misuse.Copyright © 2021 Elsevier B.V. All rights reserved.

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