Smokescreen: A Targeted Genotyping Array and Software Application for Nicotine Research
Tobacco dependence is associated with increase risk of disease and premature death. While public health and pharmacological interventions have made good progress in reducing the overall rate of smoking, challenges remain in optimizing their effectiveness based on patient characteristics including genetic variation. In order to maximize collaborative efforts to advance tobacco research, we have developed a solution called Smokescreen consisting of two major components – a targeted genotyping array and a centralized software application. We present the design of our array, which includes multi-population coverage of 1,015 genomic regions associated with addiction, as well as biological pathways related to the metabolism of nicotine and the brain’s reward system. The Smokescreen genotyping array includes a genome-wide core (296,038 SNPs); loss of function and exonic SNPs in the selected genomic regions (44,274); pharmacogenomics SNPs (2,031); eQTLs (5,870); ancestry informative markers (5,419); replicated genome-wide association studies findings (5,669); fine mapping of chr15q25, CYP2A6, and CYP2B6 (8,150); tagging of the selected 1,015 regions (205,579); and high priority SNPs identified in the literature related to smoking phenotypes and co-morbidities. We also present the centralized software application specifically designed to complement the array. The software features automated quality control, data analysis pipelines, and the ability for researchers from different institutions to combine their data for powerful analyses. The software integrates databases, cloud computing, algorithms for analysis, and a web-based user interface. We conclude by describing analytic extensions to the platform for multivariable modeling of nicotine metabolism pathways.
FUNDING: This project has been funded in whole or in part with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN271201300004C.
JUSTIFICATION: The data gathered can be used in the development of biomarkers for smoking cessation.
2014 Society for Research on Nicotine and Tobacco 20th Annual Meeting, February 5-8, 2014, Seattle, Washington, USA
James Baurley1,2, Christopher Edlund1,3, Brian Malone1, Carolyn Ervin1, Michael Hutchinson1, Bens Pardamean2, David Conti3, Adam Leventhal3, Edythe London4,Gary Swan5, and Andrew Bergen5,
1BioRealm, LLC; 2Bina Nusantara University; 3University of Southern California; 4University of California, Los Angeles; 5SRI International
