Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries

Conclusions:
This meta-GWAS of the NMR identifies CYP2A6 variants, replicates the top-ranked single nucleotide polymorphism from a recent Finnish meta-GWAS of the NMR, identifies functional mechanisms, and provides pan-continental population biomarkers for nicotine metabolism.

Implications:
This multiple ancestry meta-GWAS of the laboratory study-based NMR provides novel evidence and replication for genome-wide association of CYP2A6 single nucleotide and insertion–deletion polymorphisms. We identify three regions of genome-wide significance: proximal, intronic, and distal to CYP2A6. We replicate the top-ranking single nucleotide polymorphism from a recent GWAS of the NMR in Finnish smokers, identify a functional mechanism for this intronic variant from in silico analyses of RNA-seq data that is consistent with CYP2A6 expression measured in postmortem lung and liver, and provide additional support for the intergenic region between CYP2A6 and CYP2A7.

Source: Nicotine and Tobacco Research - August 9, 2016 Category: Addiction Authors: Baurley, J. W., Edlund, C. K., Pardamean, C. I., Conti, D. V., Krasnow, R., Javitz, H. S., Hops, H., Swan, G. E., Benowitz, N. L., Bergen, A. W. Tags: Original Investigation Source Type: research