Genetics of Alcohol and Nicotine Addiction by Dr Penelope Lind

Alcohol and nicotine addiction are major public health problems within Australia. As well as the personal and economic costs associated with dependence, there is a wide range of downstream health effects from both heavy drinking and smoking. Investigation of the causes of dependence is central to understanding and reducing the health consequences of alcohol and smoking because dependence, or addiction, drives the use of these substances and makes it extremely difficult to give them up.

There is substantial evidence that people differ in their susceptibility to alcohol or nicotine dependence, and some genetic effects predispose to both these conditions and others to only one. We proposed to conduct a comprehensive genome wide association (GWA) study by genotyping >1,000,000 polymorphisms in 2148 unrelated alcohol and nicotine dependent cases and controls to systematically screen and identify genetic variants within the Australian population that affect an individual’s liability to developing alcohol dependence (AD), nicotine dependence (ND) or both.

To allow for an efficient and cost-effective study, a pooling design was utilised for the GWA scan (Stage 1), with provision for replication in independent samples outside of Australia (Stage 2). Stage 1 was funded directly from this AHRGS application. We have completed GWA scans in quadruplicate on pools constructed from individuals meeting criteria for: (i) AD only; (ii) ND only; (iii) co-occurring AD and ND; and (iv) no history of AD or ND. Pools were also constructed separately for each sex, allowing for the examination of possible sex-specific effects, resulting in a total of 8 pools. Stage 1 genotype data has been analysed (with an exciting find on chromosome 11 for ND) and collaborators will attempt to replicate this finding and our most significant polymorphisms (initially focussing on the smoking phenotype) in independent samples from Germany and the Netherlands in January and February, 2009.