Finding the genetic markers that influence complex, multigenic substance addiction phenotypes has been an area of significant medical study. Understanding complex disease traits like addiction has been hampered by the lack of functional insights into novel variants to the human genome. We hypothesized that gene location plays a role in functional genomic neighborhoods.
To test whether there is a relationship between opiate, dopamine, and GABA disease and population allele frequencies, we used genes obtained from addiction literature curated by the National Center for Biotechnology Information (NCBI). These addiction and metabolism focused search terms generated opiate, dopamine, and GABA addiction results (N=587 genes). These genes were then projected onto the genome to identify cluster regions of genetic importance for substance addiction. Clusters were defined as regions of the genome with more than six genes within a 1.5Mb linear genomic window. We identified seven hotspots located on chromosomes 4, 6 (2 clusters), 10, 11, and 19. Human polymorphism data was surveyed from the 1148 individuals comprising the 11 sample populations of the HapMap Project dataset. Our analyses demonstrate that when human populations are assessed, ten candidate addiction alleles were identified. Finally assessments of public genome wide association studies show long range linkages to canonical addiction genes. This study delineates a novel method to identify novel candidate addiction variants using a systems biology approach that relies on an interdisciplinary set of data, including genomic, pathway data, and population variation. Important connections to sociological and environmental data are discussed to contextualize addiction data
