Recent advances in the genetic epidemiology and molecular genetics of substance use disorders


This article reviews current advances in the genetics of substance use disorders (SUDs). Both genetic and environmental sources of risk are required to develop a complete picture of SUD etiology. Genetic sources of risk for SUDs are not highly substance specific in their effects. Genetic and environmental risks for SUDs typically do not only add together but also interact with each other over development. Risk gene identification for SUDs has been difficult, with one recent success in identifying nicotinic receptor variants that affect risk for nicotine dependence. The impact of genetic variants on SUD risk will individually be small. Although genetic epidemiologic methods are giving us an increasingly accurate map of broad causal pathways to SUDs, gene discovery will be needed to identify the specific biological systems. Identifying these risk genes and understanding their action will require large clinical samples, and interaction between these studies and work in model organisms.

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Figure 1: Parameter estimates for the best-fitting confirmatory model for symptoms of cannabis, cocaine, alcohol, caffeine and nicotine dependence.
Figure 2: Parameter estimates for the contributions to variation in liability to psychoactive drug use of additive genetic effects (a2, red), familial environmental factors (c2, light blue) and the individual-specific environment (e2, dark blue) by year for average daily number of cigarettes, ages 13–40.
Figure 3: An example of gene-environment interaction: as parental monitoring increases, the importance of genetic factors significantly decreases, and the influence of common environmental factors becomes more important such that the most important etiological factors affecting adolescent smoking vary markedly as a function of parental monitoring.
Figure 4: Hypothetical item response curves for SUD diagnostic criteria.


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This work was supported in part by US National Institutes of Health grants DA18673 (M.C.N., H.M.), AA011408, AA017828, DA030005 (K.S.K., B.R.), AA018755, AA15416 (D.D.), DA023549 (N.G.), DA025109, DA022989, DA024413, DA027070, MH084952 (H.M.) and DA019498 (X.C.).

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Correspondence to Kenneth S Kendler.

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Kendler, K., Chen, X., Dick, D. et al. Recent advances in the genetic epidemiology and molecular genetics of substance use disorders. Nat Neurosci 15, 181–189 (2012).

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