Abstract Very large sample sizes are needed in genetic studies of complex traits and medical illnesses, and collecting such samples is expensive and time intensive. To accelerate complex genetic discovery and translation, it is critical to harness existing data quickly and efficiently. The goal of our proposal is to implement a novel and scalable online/mobile recruitment paradigm to harness the vast amount of genomic data generated through direct-to-consumer testing and to link these data to a research data warehouse containing electronic health record (EHR) information from the BJC Healthcare System. We will accomplish our goal in three aims: 1) Finalize online/mobile tools for recruiting consumer genomics customers who also are patients from the BJC Healthcare system. We have designed an online/mobile approach that enables participants to provide us with informed consent, their individual-level 23andMe genome-wide genotypes, and the key information required to link their genomic data to their research based EHR data. 2) Recruit a cohort of 23andMe customers who are also patients from the BJC Healthcare system to build a database linking their genotypes and EHR. We aim to recruit 10,000 participants by year 2, based on the size of the 23andMe sampling base, the size of the BJC Healthcare population, and the eligible participants we have already identified. 3) Building on our previous work, we will evaluate the performance of polygenic risk scores (PRS) for substance use phenotypes to predict health outcomes such as heart disease, COPD, lung cancer, and related traits. These analyses will be a proof of principle to test of the value of this database. Our electronic recruitment strategy can be easily adapted to recruitment for a variety of studies, and we will share our recruitment tools and details of our repository infrastructure with research institutions through the network developed as part of NIH Clinical and Translational Sciences Awards. It is critical that moving forward we make more efficient use of research resources, focusing on establishing data resources that can be used repeatedly in the future as opposed to recruiting participants to answer a single research question. By integrating online recruitment, existing genomic data, and research based electronic health records in a novel approach, our recruitment paradigm can rapidly attain the large cohorts needed for complex disease genetics research in a cost-effective manner. This approach will enable researchers to effectively target emerging health trends and research needs quickly and efficiently, and this approach complements the large-scale efforts underway such as All of Us.