About
Alcohol drinking, nicotine dependence and smoking are leading risk factors for global disease burden. Each of these factors has a substantial genetic component. The largest genome-wide association study investigating alcohol drinking identified only one genetic region, indicating the need to increase power to reliably discover genetic signals. A few more hits have been identified from GWAS analysis of tobacco smoking. UK Biobank provides a unique opportunity to identify novel genetic variants associated with (a) alcohol drinking, (b) tobacco smoking, and (c) both behaviours, as well as to quantify and characterise the genetic contribution to their comorbidity, with unprecedented statistical power. This research proposal is consistent with UK Biobank?s mission of health related research in the public interest. We will examine robustly the relationship between genetic variants with alcohol drinking and tobacco smoking and provide insights into biological mechanisms that might lead to these conditions. Our results will provide novel targets for treatment of alcohol use disorders and nicotine addiction and will inform risk assessment for the prevention, potentially leading to more targeted, stratified approaches to treatments and ?personalized healthcare? based on the specific needs of the individual. We will investigate cross-sectional associations of the genetic variants (genome wide association data) measured at baseline and alcohol drinking and tobacco smoking cross-sectionally. Findings will be deemed significant at a genome-wide significance level of P <1x10-8. We will then test the association between genetic variants that are robustly associated with alcohol drinking and tobacco smoking for possible interactions with other genes and/or the environment. We will then compare our findings with other data sets to refine and strengthen our results. We include the full cohort in our analysis.