The genetics of addiction-a translational perspective

A Agrawal, K J H Verweij, N A Gillespie, A C Heath, C N Lessov-Schlaggar, N G Martin, E C Nelson, W S Slutske, J B Whitfield, M T Lynskey, A Agrawal, K J H Verweij, N A Gillespie, A C Heath, C N Lessov-Schlaggar, N G Martin, E C Nelson, W S Slutske, J B Whitfield, M T Lynskey

Abstract

Addictions are serious and common psychiatric disorders, and are among the leading contributors to preventable death. This selective review outlines and highlights the need for a multi-method translational approach to genetic studies of these important conditions, including both licit (alcohol, nicotine) and illicit (cannabis, cocaine, opiates) drug addictions and the behavioral addiction of disordered gambling. First, we review existing knowledge from twin studies that indicates both the substantial heritability of substance-specific addictions and the genetic overlap across addiction to different substances. Next, we discuss the limited number of candidate genes which have shown consistent replication, and the implications of emerging genomewide association findings for the genetic architecture of addictions. Finally, we review the utility of extensions to existing methods such as novel phenotyping, including the use of endophenotypes, biomarkers and neuroimaging outcomes; emerging methods for identifying alternative sources of genetic variation and accompanying statistical methodologies to interpret them; the role of gene-environment interplay; and importantly, the potential role of genetic variation in suggesting new alternatives for treatment of addictions.

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