A framework enabling the genomic analysis of psychiatric traits across admixed populations.

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PROJECT SUMMARY/ABSTRACT Globally, neuropsychiatric disorders are the leading cause of disability. Despite recent advances in mental health genetics in Eurasian groups, major limitations remain in the understanding of psychiatric disorders in minority populations, in particular “admixed” groups of mixed ancestry. Due to the paucity of methodological approaches that account for their additional genomic complexity, admixed populations are systematically excluded from psychiatric genomic studies. Admixed populations, including African American and Latino individuals, make up more than a third of the US populace and have higher rates of some anxiety disorders including PTSD, yet these groups face severe disparities in mental health research and treatment due to being so sorely underrepresented in psychiatric genomics. To reap full and equitable benefits from efforts including All of Us, NeuroGAP, and the PGC, there is a pressing unmet need for the development of tools permitting the study of psychiatric traits in admixed peoples. The candidate proposes to address this issue by developing a suite of statistical methods, software packages, and analytical resources. Dr. Atkinson will: 1a) build a tool to allow for the integration of admixed individuals into psychiatric GWAS; 1b) aggregate a significantly expanded Native American reference panel to improve genomic inference in admixed American populations; 2a) characterize the genetic basis of traits relevant to psychiatric disorders in diverse populations of the largest biobank dataset; 2b) leverage the linkage disequilibrium in admixed individuals to improve fine-mapping; and 3) develop a statistical method that generates reliable genetic risk scores for psychiatric traits in admixed subjects. These efforts fill a major gap in existing resources and will improve our understanding of psychiatric diseases in diverse groups whom medical genomics has so far failed. These efforts are in direct line with the strategic mission of the NIMH, highlighting the crucial and timely nature of the proposed project. The proposed research and training plan were carefully designed to confer expertise in three domains: 1) phenotypes and genetic architectures of psychiatric disorders, 2) statistical methods development, and 3) professional development. These skills are fundamental to the candidate’s goal of becoming a leading investigator who develops and applies statistical genomics to understand psychiatric disorders across diverse populations. In addition to research training, Dr. Atkinson will take coursework, participate in regular seminars, attend workshops and conferences, and gain mentorship and teaching experience locally and in Africa. All research will be conducted in the Analytic and Translational Genetics Unit at Massachusetts General Hospital, the Broad Institute, and the Harvard TH Chan School of Public Health with mentorship from renowned scientists Drs. Mark Daly and Karestan Koenen. Additional guidance from leading experts Drs. Ben Neale, Alkes Price, and Jordan Smoller will ensure exceptional guidance and support. Overall, the training environment is outstanding, the mentors and advisors are world-class, the proposed studies address an urgent unmet need, and the additional skills gained in this award will poise Dr. Atkinson to establish independent leadership in population, statistical, and psychiatric genomics.