The Genetics, Neurogenetics and Pharmacogenetics of Addiction.

Abstract

Addictions are prevalent psychiatric disorders that confer remarkable personal and social burden. Despite substantial evidence for their moderate, yet robust, heritability (approx. 50%), specific genetic mechanisms underlying their development and maintenance remain unclear. The goal of this selective review is to highlight progress in unveiling the genetic underpinnings of addiction. First, we revisit the basis for heritable variation in addiction before reviewing the most replicable candidate gene findings and emerging signals from genomewide association studies for alcohol, nicotine and cannabis addictions. Second, we survey the modest but growing field of neurogenetics examining how genetic variation influences corticostriatal structure, function, and connectivity to identify neural mechanisms that may underlie associations between genetic variation and addiction. Third, we outline how extant genomic findings are being used to develop and refine pharmacotherapies. Finally, as sample sizes for genetically informed studies of addiction approach critical mass, we posit five exciting possibilities that may propel further discovery (improved phenotyping, rare variant discovery, gene-environment interplay, epigenetics, and novel neuroimaging designs).