Project

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Nicotine metabolism is informed by genetics, which potentiates the development of genomic tools to personalize treatment for smoking cessation in diverse peoples. However, few diverse groups are represented in current data sets characterizing nicotine metabolism genomics. We have collaborated with the Southcentral Foundation, the Strong Heart Study, the University of Montana and a tribe in Montana to understand both genomic and social dimensions of smoking cessation in AIAN people.

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Additional Information

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The nicotine metabolite ratio (NMR) is an established biomarker that has been used in clinical settings to identify fast and slow nicotine metabolizers, with optimized smoking cessation plans for each group. Although nicotine is metabolized predominantly by the enzyme cytochrome P450 2A6 (CYP2A6), genome wide association studies (GWAS) of smoking behaviors have identified hundreds of small-effect loci in this genetically complex trait. However, few diverse groups are represented in these data sets.

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AIAN people have the highest tobacco use rates in the US, with 48.4% of AIAN adults vs. 29.2% of white adults reporting smoking in 2012. Both genetic and epigenetic factors may contribute to variation in nicotine metabolism. We previously collaborated with the Southcentral Foundation, a primary care facility for AIAN peoples in Anchorage, Alaska, to characterize CYP2A6 and NMRs. We are currently expanding our research with the Strong Heart Study (SHS) to analyze genomic and epigenomic data from AI smokers in Arizona, Oklahoma, and the Dakotas. We are also in the initial phases of community engagement and research prioritization with a tribe in Montana and collaborators from the University of Montana, with whom we are conducting a survey of perspectives on smoking cessation and pharmacogenomics. Our long-term goal is to tailor smoking cessation treatment in AIANs and to strengthen the efficacy of culturally appropriate smoking cessation programs.

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Future Directions

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By linking biobank specimens, imputed genome-wide genotype data, linked electronic health records (EHRs) and health surveys, we plan to develop and apply Polygenic Risk Scores (PRSs, which summarize an individual’s unique genetic profile of nicotine metabolism) to a diverse sample from the Colorado Center for Personalized Medicine (CCPM) Biobank and other datasets. We will also identify novel genetic and epigenetic influences on NMR in AIAN smokers from the SHS using targeted or genome-wide approaches, and to examine the links between nicotine metabolism, smoking dose, and tobacco-related disease and death in AIAN people.