Genetics of Smoking Behaviors in American Indians

Henderson, Jeffrey A.; Buchwald, Dedra; Howard, Barbara V.; Li, Yafang; Tyndale, Rachel F.; Amos, Christopher I.; Gorlova, Olga Y.

doi:10.1158/1055-9965.epi-20-0026

Cited by 3 publications

(1 citation statement)

References 58 publications

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“…Other variants may affect common pathways, such as variants associating with two or more classes of psychoactive substances (e.g. BDNF 7,19,20 , PDE4B 7,20,21 or DRD2 7,15,18,20,22 ) or behavioural phenotypes (e.g., the top variant identified for cannabis use disorder, which also associates with ADHD and risk-taking 23 ).…”

Section: Introductionmentioning

confidence: 99%

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Schoeler

Baldwin

Allegrini

et al. 2021

Preprint

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Addiction to nicotine, alcohol and cannabis commonly co-occurs, which is thought to partly stem from a common heritable liability. To elucidate its genetic architecture, we modelled the common liability to addiction, inferred from genetic correlations among six measures of dependence and frequency of use of nicotine, alcohol and cannabis. Forty-two genetic variants were identified in the multivariate genome-wide association study on the common liability to addiction, of which 67% were novel and not associated with the six phenotypes. Mapped genes highlighted the role of dopamine (e.g., dopamine D2 gene), and showed enrichment for several components of the central nervous systems (e.g., mesocorticolimbic brain regions) and molecular pathways (dopaminergic, glutamatergic, GABAergic) that are thought to modulate drug reinforcement. Genetic correlations with other traits were most prominent for reward-related behaviours (e.g., risk-taking, cocaine and heroin use) and mood (e.g., depression, insomnia). These genome-wide results triangulate and expand previous preclinical and human studies focusing on the neurobiological substrates of addiction, and help to elucidate the common genetic architecture underlying addiction.

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Section: Introductionmentioning

confidence: 99%

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Schoeler

Baldwin

Allegrini

et al. 2021

Preprint

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Novel Biological Insights Into the Common Heritable Liability to Substance Involvement: A Multivariate Genome-wide Association Study

Schoeler

Baldwin²,

Allegrini³

et al. 2023

Biological Psychiatry

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Identification of Sociodemographic, Clinical, and Genetic Factors to Aid Alaska Native and American Indian People to Successfully Quit Smoking

Avey,

Schaefer,

Noonan

et al. 2023

Nicotine and Tobacco Research

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Introduction Alaska Native and American Indian (ANAI) people have a smoking prevalence of 23%. Nicotine metabolite ratio (NMR) and genetic testing may enable tailored selection of tobacco cessation medication. The purpose of this study was to evaluate the relative contributions of NMR, cessation medication, demographics, and tobacco use history to cessation. Methods Participants were recruited into an observational cohort study consisting of a baseline visit prior to their quit date and 6 week follow-up. Demographic and tobacco use surveys and blood, urine, and breath samples were collected at each visit. Electronic health records were queried for cessation medications. NMR was categorized into slow or normal nicotine metabolism phenotypes (<0.31 and ≥0.31 respectively). The main outcome was cessation at 6 weeks. Analyses consisted of descriptive statistics, medication/phenotype concordance, and estimates of relative risk of quitting. Results We enrolled 151 ANAI adults who smoked cigarettes daily. Two-thirds had normal nicotine metabolism phenotype. Retrospective medication/phenotype concordance was 39%. The overall quit rate was 25%. No demographic factors or tobacco use history were associated with quit success. Varenicline and bupropion increased the likelihood of quitting (RR=2.93 [1.42, 6.03] and RR=2.52 [1.12, 5.64] respectively) compared to nicotine replacement therapy. Non-optimal medication/phenotype concordance decreased likelihood of quit success (RR=0.44 [0.22, 0.91]) compared to optimal concordance. Conclusion This exploratory study found associations between quit success and tobacco cessation medication as well as medication/phenotype concordance. Additional research is needed to assess use of NMR for treatment selection among ANAI people. Implications These results broadly support additional community-engaged research to improve medication/phenotype concordance in tribal health settings. Such interventional research holds promise to improve expectations, quit success, and health outcomes amongst individuals attempting to quit smoking.

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Genetics of Smoking Behaviors in American Indians

Cited by 3 publications

References 58 publications

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Novel insights into the common heritable liability to addiction: a multivariate genome-wide association study

Novel Biological Insights Into the Common Heritable Liability to Substance Involvement: A Multivariate Genome-wide Association Study

Identification of Sociodemographic, Clinical, and Genetic Factors to Aid Alaska Native and American Indian People to Successfully Quit Smoking

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