FEATURE ARTICLE
Predicting Addiction
Behavioral genetics uses twins and time to decipher the origins of addiction and learn who is most vulnerable
Lisa Legrand, William Iacono, Matt McGue
The Future of Addiction Research
This complex interplay of genes and environments makes progress slow. But investigators have the data and statistical tools to answer many important addiction-related questions. Moreover, the tempo of discovery will increase with advances in molecular genetics.
In the last fifteen years, geneticists have identified a handful of specific genes related to alcohol metabolism and synapse function that occur more often in alcoholics. But the task of accumulating the entire list of contributing genes is daunting. Many genes influence behavior, and the relative importance of a single gene may differ across ethnic or racial populations. As a result, alcoholism-associated genes in one population may not exert a measurable influence in a different group, even in well-controlled studies. There are also different pathways to addiction, and some people's alcoholism may be more environmental than genetic in origin. Consequently, not only is any one gene apt to have small effects on behavior, but that gene may be absent in a substantial number of addicts.
Nonetheless, some day scientists should be able to estimate risk by reading the sequence of a person's DNA. Setting aside the possibility of a futuristic dystopia, this advance will usher in a new type of psychology. Investigators will be able to observe those individuals with especially high (or low) genetic risks for externalizing as they respond, over a lifetime, to different types of environmental stressors.
This type of research is already beginning. Avshalom Caspi, now at the University of Wisconsin, and his colleagues divided a large group of males from New Zealand based on the expression level of a gene that encodes a neurotransmitter-metabolizing enzyme, monoamine oxidase A or MAOA. In combination with the life histories of these men, the investigators demonstrated that the consequences of an abusive home varied by genotype. The gene associated with high levels of MAOA was protective—those men were less likely to show antisocial behaviors after childhood maltreatment than the low-MAOA group.
Further advances in molecular genetics will bring opportunities for more studies of this type. When investigators can accurately rank experimental participants by their genetic liability to externalizing, they will gain insight into the complexities of gene-environment interplay and answer several intriguing questions: What type of family environments are most at-risk children born into? When children with different genetic risks grow up in the same family, do they create unique environments by seeking distinct friends and experiences? Do they elicit different parenting styles from the same parents? Could a low-risk sibling keep a high-risk child from trouble if they share a close friendship? Is one type of psychosocial stressor more apt to lead to substance use while another leads to antisocial behavior?
Molecular genetics will eventually deepen our understanding of the biochemistry and biosocial genesis of addiction. In the interim, quantitative geneticists such as ourselves continue to characterize the development of behavior in ways that will assist molecular geneticists in their work. For example, if there is genetic overlap between alcoholism, drug dependence and antisocial behavior—as the MCTFR data suggest—then it may help to examine extreme externalizers, rather than simply alcoholics, when searching for the genes that produce alcoholism vulnerability.
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