Genetic contributions to individual differences in vulnerability to addiction and abilities to quit

George R. Uhl, Tomas Drgon

Research output: Chapter in Book/Report/Conference proceedingChapter


Individuals differ in their vulnerabilities to becoming dependent on one or more abused substances. Not all of the individuals who have opportunities to use addictive substances do in fact use them, not all users become regular users or abusers and not all regular users or abusers become dependent or addicted. Abundant evidence from family, adoption, and twin studies point to large genetic contributions to individual differences in vulnerability to develop dependence on addictive substances. Twin data suggests that much of this genetic vulnerability is shared by individuals who are dependent on a variety of addictive substances, though some is likely to be substance specific. Substance-dependent individuals also differ in their abilities to quit use of addictive substances and to maintain abstinence. Twin data for abilities to quit smoking provide some of the best evidence for genetic influences on abilities to achieve and maintain abstinence on an addictive substance. These estimates for overall genetic contributions still leave open a variety of possibilities concerning the genetic architectures that underlie these addiction vulnerability and quit success phenotypes. Current molecular genetic data relevant to each of these phenotypes fit with the idea that each displays largely polygenic influences. Major gene effects have been identified for alcohol dependence in Asians with the flushing syndrome and for low-level cigarette use (chippers) with modest signs of physiological nicotine dependence at a chromosome 15 nicotinic receptor locus. Genes identified in molecular genetic studies of addiction vulnerability and quit success phenotypes partially overlap, as we would expect from classical genetic studies, and fall into several functional classes more than expected by chance. These data provide a substrate to improve understanding of substance dependence and the ability to quit smoking. With better understanding of genetic influences on these phenotypes, we may be better positioned to improve understanding of the large environmental influences on these phenotypes, to personalize treatments, and even to personalize prevention strategies for individuals at especial risk.

Original languageEnglish (US)
Title of host publicationDrug Abuse and Addiction in Medical Illness: Causes, Consequences and Treatment
PublisherSpringer New York
Number of pages11
ISBN (Print)9781461433750, 1461433746, 9781461433743
StatePublished - Jul 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)

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