Greater availability of personalized genetic information regarding the efficacy or toxicity of medications could lead to improved patient care and save consumers, insurers and medical institutions billions of dollars per year. Although the field of pharmacogenomics has had some success in discovering relationships between genetic variants and drug response, a great deal of genetic variation in drug response remains unexplained. Our broad, long term research aim is to identify novel pharmacogenetic associations using web-based phenotyping of efficacy and toxicity for several major drug classes. With that goal in mind, our short term aim is to determine whether web-based collection of phenotype data along with genome-wide data for thousands of 23andMe customers leads to replication of known associations between responses to proton pump inhibitors (PPIs) and the gene CYP2C19, and between responses to several commonly used medications and the gene CYP2C9. The specific aims of this study are (1) to develop and administer web-based surveys to collect information regarding response to several commonly used classes of medications (including antihistamines, analgesics, blood thinners, and proton-pump inhibitors) from at least 3,000 individuals; and (2) to determine whether this web-based research model yields replications of known associations between several commonly used medications and the genes CYP2C19 and CYP2C9. To conduct this innovative study the 23andMe research group will leverage several resources, including a broad set of drug metabolism-related single nucleotide polymorphisms (SNPs) on the 23andMe custom genotyping array. This project will also leverage involvement of a rapidly expanding, engaged, genotyped cohort of 23andMe customers who have the option to participate in research by responding to web-based questionnaires. The parallel and continuous nature of this research model allows for the efficient recruitment of participants to many studies at once and reduces the cost of re-contacting for additional analyses. As evidence of our rapid capability to assemble a cohort, an initial survey regarding commonly used medications solicited, within a month, responses from about 2500 individuals genotyped at 580,000 SNPs. Possible outcomes of this study include the replication of known pharmacogenomic associations and the discovery of novel associations. If the study is successful in yielding replications, it will set the stage for rapid, well-powered and cost-effective research on variation in response to a large number of medications, thereby significantly advancing personalized medicine. PUBLIC HEALTH RELEVANCE: The availability of personalized genetic information regarding the efficacy or toxicity of medications could lead to improved patient care, and save consumers, insurers and medical institutions billions of dollars per year. With that goal in mind, our near term aim in this grant is to determine whether web-based collection of phenotype data along with genome-wide data for thousands of 23andMe customers leads to replication of known associations two genes (CYP2C9 and CY2C19) and several major drug classes of commonly used medications.