ABSTRACT This R21 project implements an innovative online/mobile recruitment and assessment strategy and applies it to identify genetic factors that influence cannabis use and related medical risks and benefits. Too often, recruiting and developing sufficiently large cohorts for human genetic studies has been slow and expensive. Our approach will greatly reduce time and costs by recruiting already-genotyped consumer genomics customers and electronically assessing their substance use via mobile devices and the internet. The proposed work builds on our prototype Genomics of Addiction (GENA) mobile app that earned third prize in the 2016 NIDA Challenge “Addiction Research: There's an App for That” (https://www.drugabuse.gov/researchers/research- resources/nida-challenges-program). Specifically, to identify loci involved in cannabis use and related medical risks and benefits, we will: (1) Finalize and implement our “direct-to-participant” interface, which allows participants to use our mobile app and website to provide informed consent, answers to cannabis use questions, and secure access to their existing genome-wide genotype data; (2) Recruit and electronically assess a large, well-powered cohort for a genome-wide association study (GWAS) of cannabis use traits important to public health; (3) Analyze our new GWAS cohort to identify loci associated with medically relevant cannabis use traits and quantitative frequency of use. Our novel, direct-to-participant protocol will immediately address a high-priority substance, cannabis, and establish a platform for responding to emerging research needs in the substance use field.