Alcohol and cigarette smoking consumption as genetic proxies for alcohol misuse and nicotine dependence

Purpose: To investigate the role of consumption phenotypes as genetic proxies for alcohol misuse and nicotine dependence. Methods: We 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 medicalcenter 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 Fagerstro?m Test for Nicotine Dependence from non-UKB cohorts. Results: In 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. Conclusions: Our 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.