An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population

Abstract

Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual.