GABRA2

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Alcohol dependence is a highly prevalent disorder that is associated with serious morbidity and mortality. Alcohol dependence has a significant heritable component estimated to account for 50-60% of risk. We have recently used a Connecticut sample of 258 Caucasian alcohol dependent and 335 screened controls to confirm an association of alcohol dependence with the GABRA2 gene reported in an abstract at the Research Society on Alcoholism in 2003. We found a 7% excess frequency (44% vs. 37%) of a seven-marker haplotype extending 98,000 bp over the 3'-half of the GABRA2 gene for subjects with alcohol dependence. We are now proposing to extend our case control association investigations of the GABRA2 gene and alcoholism by examining a more diverse multi-center sample of 1100 alcoholic subjects collected in project MATCH (a multi-center alcoholism treatment trial) with a collection of 1100 control subjects. We will use this sample to extend our observations in several ways: i) to test for the association in a larger and more geographically diverse sample, ii) to use additional markers to better define the 3'-endpoint of association, iii) potentially focus the area of association by use of a larger and more genetically diverse sample iii) to examine for association with subtypes of alcohol dependent phenotype and co-morbid conditions. We will use the Duffy antigen as an initial screen for differences in Caucasian versus Black chromosome admixture in the MATCH versus control sample from the NYC Cancer Project. If significant differences are detected we will plan to collaborate with Dr. Joel Gelernter at Yale whose laboratory has developed techniques using a panel of racially informative markers to allow statistical correction case-control genetic associations. A second aim will be to examine human GABRA2 Carrier Deoxyribonucleic Acid (cDNA) clones for splice or coding sequence changes in linkage with a known exon 4 synonomous Single nucleotide polymorphism (SNP) present at higher frequency in alcoholics in our initial sample.