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  • Can Your Genes Make You Do It?Author(s): Linda Martin-Morris, Helen T. Buckland and Susanna L. CunninghamSource: The American Biology Teacher, Vol. 74, No. 9 (November/December 2012), pp. 652-653Published by: University of California Press on behalf of the National Association of BiologyTeachersStable URL: .Accessed: 13/05/2014 17:41

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  • 652 The american biology Teacher volume 74, no. 9, november/December 2012

    Genetic Predisposition to AddictionA friend used to say I dont gamble because I have an addictive personality. She felt that she was somehow predisposed to lose voli-tional control over her gambling. Indeed, curi-osity about a putative genetic predisposition to addiction has not been restricted to a few would-be gambling addicts.

    It is estimated that 4060% of the addic-tion trait is controlled by gene products (Uhl, 2004). For example, the risk of becoming an alcoholic is elevated five- to eightfold if a pri-mary relative is an alcoholic (Merikangas et al., 1998). For twins, genetically identical pairs show more sharing of alcoholism than fraternal twin pairs (Prescott & Kendler, 1999). But what are the genes implicated in addiction?

    The thirst for understanding of, and potentially treatment for, addiction has pres-sured many to jump hastily to the conclusion that THE addiction gene has been identified. But it is clear that addiction, like any complex behavioral trait, is influenced by MANY genes and that these genes are only part of the story. An estimated 1500 (or more) genes influence addictive behaviors (Li et al., 2008). This com-plexity means that a prediction about an indi-viduals risk is impossibly hard to make. But it does not prevent us from trying to identify spe-cific genes associated with addiction.

    There are two main methods for identifying genes that predispose a person to addiction. The candidate-gene approach is hypothesis-driven but biased. It starts by hypothesizing that a specific gene (and therefore is biased to the genes one wants to investigate) involved in some drug-related process or pathway, if mutated, could influence the users experience with the drug. Many genes have been investigated in this candidate-gene approach (Goldman et al., 2005). For instance, alleles that manufacture nonoptimal versions of many drug- metabolizing enzymes result in a reduced frequency of drug use. The candidate-gene approach has also led to the anal-ysis of genes that make receptors to which drugs

    or neurotransmitters bind. Because the reward pathway we previously discussed (Cunningham et al., 2012) is involved in addiction to many drugs, the dopamine-receptor encoding gene, D2DR, has been strongly implicated in a complex trait referred to as reward deficiency syndrome (Blum et al., 1996). In summary, the candidate-gene approach has led to many fruitful discov-eries about genes that specifically influence drug response as well as those that might more gener-ally predispose a person to use substances.

    A genome-surveillance approach (Liu et al., 2005) is less biased because it makes no assump-tions about the nature of the proteins encoded

    by addiction-influencing genes. However, this approach has been likened to finding the prover-bial needle in the haystack. The human genome has some 25,000 genes. Nearly 1500 of them have been implicated in some way in addiction (Li et al., 2008). How do we find the ones cor-related with a specific behavior? The answer involves years, an international collection of labs, and an extremely thorough bioinformatics analysis. In 2009, just such a bioinformatics approach investigated 30 years worth of research encompassing more than 2000 studies (Li & Bur-meister, 2009, fig. 1). This analysis focused on five genetic pathways, including old standards

    The American Biology Teacher, vol. 74, no. 9, pages 652653. iSSn 0002-7685, electronic iSSn 1938-4211. 2012 by national association of biology Teachers. all rights reserved. request permission to photocopy or reproduce article content at the university of california Presss rights and Permissions Web site at Doi: 10.1525/abt.2012.74.9.10

    ADDICTION Can Your Genes Make You Do It? & THE BRAIN

    L i n d a M a r t i n - M o r r i s , H e L e n t. B u c k L a n d, s u s a n n a L . c u n n i n g H a M

    Figure 1. Genes mapped to 11 of our 23 chromosomes are implicated in single-drug addiction or, in some cases, addiction to multiple substances (from Li & Burmeister, 2009). See ABT online for color figure.

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  • The american biology Teacher aDDicTion & The brain 653

    as well as new gene candidates that are impli-cated in addiction, generally. These pathways include the glutamate-reinforcing pathway, a pathway implicated in learning and memo-ries related to addiction, and one that involves MAPK (mitogen- activated protein kinase), which may underlie synaptic changes that occur during use of addictive drugs. Again, they point to the importance of the reward pathway but also illu-minate other important aspects of brain func-tion, such as glutamate systems.

    Although genetics can predispose a person to addiction, it is irresponsible to imagine that a person can reasonably blame genes for addic-tion. Similarly, a person with predisposing alleles should not despair that addiction is inevitable. You have to participate in the use of an addictive substance to become an addict. Understanding ones genetic predisposition can actually help an individual avoid behaviors that could lead to addiction. As with the woman who avoided gambling because she had an addictive person-ality, avoiding addictive habits is entirely pos-sible. In addition, addictive patterns can also be turned around; this same courageous woman overcame a three-pack-a-day nicotine addiction that had plagued her for 46 years.

    The next piece in this series will high-light the role of learning in addiction. Recent

    evidence suggests that this may be an impor-tant factor to consider. Join us to explore the evidence underlying this premise.

    AcknowledgmentsThis project was funded by the National Insti-tute on Drug Abuse, National Institutes of Health, through grant no. R25DA028796.

    Referencesblum, K., Sheridan, P.J., Wood, r.c., braverman, e.r.,

    chen, T.J., cull, J.g. & comings, D.e. (1996). The D2 dopamine receptor gene as a determinant of reward deficiency syndrome. Journal of the Royal Society of Medicine, 89, 396400.

    cunningham, S., buckland, h.T. & martin-morris, l. (2012). What is the link between eating, reproducing, & addiction? American Biology Teacher, 74, 590591.

    goldman, D., oroszi, g. & Ducci, F. (2005). The genetics of addictions: uncovering the genes. Nature Review Genetics, 6, 521532.

    li, c.-y., mao, X. & Wei, l. (2008). genes and (common) pathways underlying drug addiction. PLoS Computational Biology, 4(1), e2.

    li, m.D. & burmeister, m. (2009). new insights into the genetics of addiction. Nature Reviews Genetics, 10, 225231.

    liu, Q.r., Drgon, T., Walther, D., Johnson, c., Poleskaya, o., hess, J. & uhl, g.r. (2005). Pooled association genome scanning: validation and

    use to identify addiction vulnerability loci in two samples. Proceedings of the National Academy of Sciences USA, 102, 1186411869.

    merikangas, K.r., Stolar, m., Stevens, D.e., goulet, J., Preisig, m.a., Fenton, b., Zhang, h., omalley, S.S. & rounsaville, b.J. (1998). Familial transmission of substance use disorders. Archives of General Psychiatry, 55, 973979.

    Prescott, c.a. & Kendler, K.S. (1999). genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. American Journal of Psychiatry, 156, 3440.

    uhl, g.r. (2004). molecular genetic underpinnings of human substance abuse vulnerability: likely contributions to understanding addiction as a mnemonic process. Neuropharmacology, 47(Supplement 1), 140147.

    SuSanna l. cunningham is Professor at the university of Washington, School of nursing, T618b health Sciences, 1959 ne Pacific Street, Seattle, Wa 98195-7266; e-mail: helen T. bucKlanD is Project Director of the online neuroscience education about Drug addiction at


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