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Mapping of Genetic Loci for Nicotine Dependence

Institution: Ernest Gallo Clinic and Research Center
Investigator(s): Kirk Wilhelmsen, M.D., Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7PT-2003 Award: $982,095
Subject Area: Epidemiology
Award Type: Integrated Research Project

Initial Award Abstract
People who smoke probably do so because environmental influences and inherited biological factors interact in complex ways. Genetic epidemiology studies in families and in twins have attempted to clarify some of these interactions. Environmental influences, such as parental smoking, largely determine whether an individual ever tries tobacco at all. In contrast, genetic factors probably influence how pleasant or unpleasant that first experience is. Environmental effects, such as social support for smoking, play an important role in maintaining early tobacco use. Persistent smoking signals nicotine addiction in which biological factors, including genetic susceptibility, are important. Over the past 40 years, public policy changes, such as publicizing the harmful effects of smoking, imposing cigarette taxes, and restricting access to tobacco by minors, have been implemented in the United States, and the proportion of the population that smokes has dropped dramatically.

It is encouraging that altering environmental factors can decrease smoking. However, tobacco use remains an important public health problem despite such efforts, suggesting that biologically based interventions might be necessary to realize further decreases in smoking and its negative health consequences. Human genetic analysis, which compares the similarities and differences in DNA segments between family members who do or do not have a particular illness, has allowed disease-causing genes to be identified for many conditions. We propose to compare this information against similarities and differences in DNA sequences to identify genes that influence persistent tobacco use. Identifying such genes could improve our understanding of the biological causes of smoking, eventually leading to biologically based therapies for nicotine addiction.