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Cited by 71Substance Abuse Treatment and OutcomesGenetic Associations and EpidemiologyNeurotransmitter Receptor Influence on Behavior

Evidence for a Genetic Component for Substance Dependence in Native Americans

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Ehlers, Cindy L., Gizer, Ian R.·2013·American Journal of Psychiatry
DOI 10.1176/appi.ajp.2012.12010113PMC PMC3603686
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Abstract

OBJECTIVE: Although tribes differ with regard to the use of alcohol and drugs, substance dependence is one of the primary sources of health problems facing Native Americans. General population studies have demonstrated that substance dependence has a substantially heritable component (approximately 50% of the risk resulting from genetic influences); however, fewer studies have investigated the role of genetics in the risk for substance dependence in Native Americans. METHOD: The authors present a literature review of the evidence for a genetic component in the etiology of substance dependence in Native Americans, including studies of heritability, linkage analyses, and candidate genes. RESULTS: Evidence for the heritability of alcohol and drug dependence was found. Linkage analyses revealed that genes influencing risk for substance dependence and related phenotypes, such as body mass index (BMI), drug tolerance, EEG patterns, and externalizing traits, reside on several chromosome regions identified in other population samples. Overlap in the gene locations for substance dependence and BMI suggests that a common genetic substrate may exist for disorders of consumption. Studies of the genes that code for alcohol-metabolizing enzymes have not revealed any risk variants specific to Native American populations, although most Native Americans lack protective variants seen in other populations. Other candidate genes associated with substance dependence phenotypes in Native Americans include OPRM1, CRN1, COMT, GABRA2, MAOA, and HTR3-B. CONCLUSIONS: Substance dependence has a substantial genetic component in Native Americans, similar in magnitude to that reported for other populations. The high rates of substance dependence seen in some tribes is likely a combination of a lack of genetic protective factors (metabolizing enzyme variants) combined with genetically mediated risk factors (externalizing traits, consumption drive, and drug sensitivity or tolerance) that combine with key environmental factors (trauma exposure, early age at onset of use, and environmental hardship) to produce an elevated risk for the disorder.

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  • The effect of genetic variants such as ALDH2*2 and ADH1B*3 on SUD among AIAN has not been studied thoroughly.

    “Reviewed studies indicate AIAN appear to lack metabolizing enzyme genes, similar to other population groups (East Asian and some Africans) (e.g., ALDH2*2 and ADH1B*3), but the effect of these genetic variants on SUD among AIAN has not been studied thoroughly [46].”

    From Substance and Behavioral Addictions among American Indian and Alaska Native Populations (2022) · cites this paper as [46]

    The Discussion and Conclusions (page unavailable) says larger studies across more tribal groups are needed, supporting the claim that the evidence remains limited. But the Results (page unavailable) report that ADH1B*3 has already been associated with reduced alcohol-dependence risk in a California Indian sample; the paper does not establish effects on substance use disorders broadly. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Reviewed studies indicate AIAN appear to lack metabolizing enzyme genes, similar to other population groups (East Asian and some Africans) (e.g., ALDH2*2 and ADH1B*3).

    “Reviewed studies indicate AIAN appear to lack metabolizing enzyme genes, similar to other population groups (East Asian and some Africans) (e.g., ALDH2*2 and ADH1B*3), but the effect of these genetic variants on SUD among AIAN has not been studied thoroughly [46].”

    From Substance and Behavioral Addictions among American Indian and Alaska Native Populations (2022) · cites this paper as [46]

    The Discussion and Conclusions says that some Native American tribes appear to lack protective variants in alcohol-metabolizing enzyme genes, including ALDH2*2 and ADH1B*3, and calls for larger studies across more tribal groups. The claim overgeneralizes this to AIAN as a whole and says they lack the genes rather than particular variants. The Results also report ADH1B*3 in a California Indian sample. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • It has been theorized that AIANs are less likely to have the protective variant genes to metabolize alcohol.

    “It has been theorized that AIANs are less likely to have the protective variant genes to metabolize alcohol.”

    From Substance and Behavioral Addictions among American Indian and Alaska Native Populations (2022) · cites this paper as [46]

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Authors
Ehlers, C. L., & Gizer, I. R.
Affiliations
Scripps Research Institute (US)
ORCID
Venue
American Journal of Psychiatry
Publisher
American Psychiatric Association Publishing
Published
2013-02
Volume
170
Issue
2
Pages
154-164
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
DOI
10.1176/appi.ajp.2012.12010113
PMC
PMC3603686
OpenAlex
W2125740962
Cited by
71
References
1
Citations by year
2026: 2 · 2025: 9 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 10 · 2020: 5 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 2 · 2014: 6 · 2013: 1
FWCI
0.63
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute on Alcohol Abuse and Alcoholism (R37AA010201, AA010201, R01AA010201)
  • National Institute on Drug Abuse (DA030976, R01DA030976)
Topics
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
substance dependence, Native Americans, heritability, genetic susceptibility, alcoholism, drug addiction, linkage analysis, candidate genes, body mass index, alcohol-metabolizing enzymes, OPRM1, catechol-O-methyltransferase, monoamine oxidase A, GABRA2, HTR3B, externalizing traits, drug tolerance, trauma exposure
MeSH terms
Genes, Overlapping, Humans, Indians, North American, Genetic Linkage, Polymorphism, Genetic, Risk Factors, United States, Substance-Related Disorders, Genetic Predisposition to Disease, Inheritance Patterns, Genome-Wide Association Study, Genetic Association Studies, Gene-Environment Interaction

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