Unfortunately, the current data do not provide us with the exact information with any degree of certainty. Clearly, further genotyping of this region to define the exact haplotype blocks and resequencing to define the exact sequence of those blocks is indicated in this and other samples. Perhaps then, after the sequence data is skillfully bioinformatically interrogated and animal modeling and CNS gene expression studies are conducted, the exact nature of the variants associated with illness can be revealed. We tried to examine the effects of GABRA2 genotype on gene expression using the lymphoblast cell line surrogate model that we have successfully used with respect to other genetic variation [24, 25] and of direct relevance, nicotine dependence [26], but the amount of gene expression was nearly undetectable (unpublished data).
