Project Details
Projekt
Genetics of Nicotine Dependence: Clinical and Neurobiological Phenotypes in a Multicentered Case-Control-Study
Applicants
Professor Dr. Falk Kiefer; Professor Michael Wagner, Ph.D.; Professor Dr. Thomas F. Wienker; Professor Dr. Georg Winterer
Subject Area
Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Term
from 2006 to 2010
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 31025545
One-third of adults worldwide are smokers and in 2000, smoking caused about 2.5 million deaths in industrialized countries. In the biopsychosocial model of nicotine dependence, the highly addictive nature of tobacco consumption is thought to be rooted to some considerable extent in the neurobiological effects of smoking and the individual neurobiological disposition to develop nicotine dependence. Furthermore, nicotine dependence is now believed to be a complex, polygenic disorder. Twin and adoption studies have suggested that heritabilrties for smoking initiation and smoking persistence are in the range of 59% in males and 46% in females. In addition, it is now increasingly recognized that nicotine-dependence cannot be considered as a unitary phenomenon but that different smokers may smoke for different reasons. For instance, concordance tests across multiple measures of dependence indicated that these different measures might tap into different aspects of nicotine dependence. Alcohol consumption, lifestyle factors, environmental factors, personality traits such as reward dependence and psychiatric disorders are also known to be correlated with nicotine dependence Some of these factors may undergo changes during abstinence, which in turn may lead to relapse. In previous studies on the genetics of nicotine dependence, no group worldwide has taken into account this heterogeneity and there is currently hardly any gene that has been consistently associated with nicotine dependence. Therefore, in the proposed study on the genetics of nicotine dependence, we will take into account this heterogeneity and adopt the so-called endophenotyping strategy, i.e., rather than solely comparing nicotine-dependent vs non-dependent subjects, we will also investigate nicotine dependence-related phenotypes such as personality, cognitive perfromance, electrophysiological markers of attention and filtering, or stress-related hormone levels etc. This way, we expect to increase stastical power plus to better understand the neurobiological effects of genes that are involved in nicotine dependence. During the first funding period, data will be collected from a sample consisting of n = 1000 nicotine-dependent subjects compared with n = 1000 never-smoking subjects. Saliva from parents of the affected probands will also be collected to conduct TDT analyses; this will be particularly important for a replication study using recently developed statistical methods. Furthermore, we will investigate n = 500 non-dependent smokers in order to obtain information on potentially existent gene-environment interactions. For the second funding period, genetic analysis will be conducted on the accruing sample, first for selected candidate genes and then for a genome wide context using high-density SNP markers. A two- or multi-stage approach with grid-tightening and staged sample utilization will be employed. Accordingly, it is planned that by then, additional funding applications will be submitted which will address different aspects of the genetics of nicotine dependence.
DFG Programme
Priority Programmes
