Alcohol and nicotine are commonly co-abused substances. Genetic studies have provided evidence that genes influence the responses to both of these drugs independently, but more recently there have been data to suggest that common gene(s) are likely to influence responses to both drugs. There is an abundant amount of animal research providing evidence that neuronal nicotinic acetylcholine receptors, in particular 1422- containing receptors are involved in the behavioral responses to nicotine. Important for this proposal, these receptors have also been implicated in sensitivity to some effects of alcohol. Nicotinic acetylcholine receptors containing the 14 and 22 subunits have been shown to play a key role in regulating dopamine release in brain regions known to be important for underlying responses to abused drugs. This proposal focuses on the role of natural variation in these receptor subunits in alcohol and nicotine behaviors. Two samples will be used to determine if single nucleotide polymorphisms (SNPs) in the genes encoding these subunits influence sensitivity to alcohol and nicotine phenotypes. DNA and phenotypic data that have already been collected from the Colorado Center for Antisocial Drug Dependence (CADD) and the National Youth Survey (NYS) studies will be available for analysis. The candidate will examine the influence of these genes using resequencing and family-based association tests. Furthermore, the SNPs found to be associated with alcohol or nicotine behaviors will be functionally characterized using luciferase-based gene expression assays. Through this project the candidate will achieve her short-term goal of learning human statistical genetics, molecular genetics and bioinformatics tools. To learn these methods the candidate will attend coursework, symposia, workshops and conferences, in addition to having regular meeting with her mentors. All mentors of this project are faculty fellows at the Institute for Behavioral Genetics. This environment is ideal for such training because of the Institute's long history in studying questions related to the genetics of substance abuse in humans and using animal and molecular approaches. This new training will complement the candidate's prior training in mouse behavioral genetics and will be important for the candidate's long-term goal of becoming an independent researcher. With this additional training in human statistical and molecular genetics the candidate hopes to ultimately evaluate translational questions between model organism and human populations.
Alcohol and nicotine are by far the most commonly co-abused substances and there is evidence that common gene(s) may underlie the response to both drugs. The proposed project will increase our knowledge of the genetic influence the responses to these drugs and may be informative for the development of treatment strategies.
|Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun et al. (2016) Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet 46:151-69|
|Melroy-Greif, Whitney E; Vadasz, Csaba; Kamens, Helen M et al. (2016) Test for association of common variants in GRM7 with alcohol consumption. Alcohol 55:43-50|
|Kamens, Helen M; Corley, Robin P; Richmond, Phillip A et al. (2016) Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence. Behav Genet 46:693-704|
|Locker, Alicia R; Marks, Michael J; Kamens, Helen M et al. (2016) Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice. Brain Res Bull 123:13-22|
|Kamens, Helen M; Miyamoto, Jill; Powers, Matthew S et al. (2015) The Î²3 subunit of the nicotinic acetylcholine receptor: Modulation of gene expression and nicotine consumption. Neuropharmacology 99:639-49|
|Melroy, Whitney E; Stephens, Sarah H; Sakai, Joseph T et al. (2014) Examination of genetic variation in GABRA2 with conduct disorder and alcohol abuse and dependence in a longitudinal study. Behav Genet 44:356-67|
|Kamens, H M; Corley, R P; McQueen, M B et al. (2013) Nominal association with CHRNA4 variants and nicotine dependence. Genes Brain Behav 12:297-304|
|Kamens, Helen M; Hoft, Nicole R; Cox, Ryan J et al. (2012) The Ã½Ã½6 nicotinic acetylcholine receptor subunit influences ethanol-induced sedation. Alcohol 46:463-71|