Admin Supplement: Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability

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All of Us Administrative Supplement to Enhance “Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability” U01 MH119690 Supplement Abstract We request an administrative supplement for our 3-site consortium entitled “Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability” U01 MH119690. The supplement will support additional work, planned and performed in our consortium and in conjunction with the larger NIMH Rare Genetic Diseases Network, to advance the primary goal of our network: elucidating the genetic architecture of mental illnesses by studying rare genetic disorders. The goal of our more focused consortium (acronym CAMP for CNVs And Major Psychopathology) is to model the impact of rare and recurrent CNVs on risk for major mental illnesses, related symptoms, and cognitive traits in approximately one million individuals who participated in prior genetics research projects and whose data is shared with the research community. Our administrative supplement, in response to NOT- PM-22-002, will facilitate the inclusion of data from the All of Us Research Program in the CAMP project. Given the racial and socioeconomic diversity in the All of Us cohort, it is critical to include this sample in the CAMP project to ensure generalizability of our findings to all of the U.S. population. The All of Us Research Program aims to advance personalized medicine by accelerating health and medical breakthroughs and enabling individualized prevention, treatment, and care. To that end, All of Us is building a database of one million volunteers who will provide medical records and biosamples to help transform the future of health research by equipping researchers nationwide with expansive health data from diverse populations, especially those underrepresented in biomedical research. To date, data from ~329,000 participants has been collected, with ~50% racial and ethnic minorities and 80% from communities underrepresented in biomedical research overall. Of these initial participants, electronic health record data are available from ~214,200 participants and ~100,000 have sharable whole genome sequence (WGS) data. In a series of video conferences, the CAMP project PIs delineated several critical opportunities for project expansions that would greatly enhance the quality of the results while remaining in line with the initial aims of our project. Thus, the goal of this administrative supplement is to use our validated pipelines to call CNVs in All of Us participants with WGS data (Aim 1) and include these subjects in ongoing CAMP analyses focused on psychopathology (Aim 2) and ancestral diversity (Aim 3). These aims are all activities that are firmly within the scientific scope of work of our original project but require additional bioinformatics and analytical personnel to implement.