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Its application promises to enable targeted drug administration, improve therapeutic outcome, and inform drug development. Pharmacogenomic insights have improved our understanding of the underlying pathways and mechanisms behind adverse drug reactions, which account for approximately 100,000 deaths per year in the US and markedly increase healthcare costs. The vast majority of pharmacogenomic association studies, which are the drivers of discovery in the field of precision medicine, have been conducted on exclusively European populations, thereby precluding the discovery of African American specific genetic biomarkers that affect drug phenotypes. Without scientific inquiry on the presence and association of these SNPs to drug response, our ability to deliver precision medicine to 1 in 7 Americans is severely hampered. To close this growing heath disparity in African American precision medicine we formed ACCOuNT and are proposing a discovery project within cardiovascular pharmacogenomics. In our Discovery project, we hypothesize that through discovery efforts centered on African Americans, we will identify predictive biomarkers of cardiovascular drug response and disease susceptibility that can be investigated in translational outcome studies. We will test this hypothesis with the following aims: 1) Determine genetic predictors of drug response to thrombotic therapy using genome-wide association methodology, 2) Investigate the role of gene expression/splice variants and eQTLs on drug response phenotypes for elucidation of biological mechanisms and genetic regulation of these phenotypes, and 3) Create a publically available and searchable database to house the results of the genomic and transcriptomic studies in African Americans. Through the infrastructure of ACCOuNT we will conduct our discovery efforts with a patient-centered approach that incorporates the input of community partners, frontline physicians and African American patients. We anticipate that these studies will reveal novel SNP associations and gene regulation pathways. Several potential research areas/questions may develop from this work. Our proposed genomics database will serve as needed resource within the pharmacogenomics scientific community, which currently lacks comprehensive genomics and transcriptomic information on African Americans. These new research avenues have the potential of feeding seamlessly into our translational project and pilot projects thus allowing us to leverage our Transdisciplinary Collaborative Center to move implementation of precision medicine in African Americans faster than previous efforts.","data_download_links":[{"guid":"dg.OADC/2c22a776-6fe7-40ca-aa01-acaa4a312ecb","title":"Clopidrogrel Study Structured Metadata in Portable Format for Biomedical Data","description":"Gen3 Portable File Format (PFB) can be manipulated by pypfb (https://github.com/uc-cdis/pypfb)"},{"guid":"dg.OADC/d16f99db-d8c3-49dc-becb-ea721c49b2af","title":"Clopidrogrel Study Structured Metadata in Zip format","description":"This is a zip archive containing all the structured metadata in TSV format for each node in the discovery-clopidogrel study."}]}},"CCLE":{"_guid_type":"discovery_metadata","gen3_discovery":{"link":"https://portals.broadinstitute.org/ccle/about","tags":[{"name":"Aligned Reads","category":"Data Type"}],"authz":"/programs/OpenAccess/projects/CCLE","source":"Broad Institute","commons":"Open Access Data Commons","funding":"Novartis","summary":"The CCLE (Cancer Cell Line Encyclopedia) project is a collaboration between the Broad Institute, and the Novartis Institutes for Biomedical Research and its Genomics Institute of the Novartis Research Foundation to conduct a detailed genetic and pharmacologic characterization of a large panel of human cancer models, to develop integrated computational analyses that link distinct pharmacologic vulnerabilities to genomic patterns and to translate cell line integrative genomics into cancer patient stratification. 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Please visit regularly!"}},"ds000030":{"_guid_type":"discovery_metadata","gen3_discovery":{"link":"https://openneuro.org/datasets/ds000030/versions/00016","tags":[{"name":"Imaging Files","category":"Data Type"}],"authz":"/programs/OpenNeuro/projects/ds000030","source":"OpenNeuro","commons":"Open Access Data Commons","funding":"Consortium for Neuropsychiatric Phenomics","summary":"The Consortium for Neuropsychiatric Phenomics (CNP) is a large study funded by the NIH Roadmap Initiative that aims to facilitate discovery of the genetic and environmental bases of variation in psychological and neural system phenotypes, to elucidate the mechanisms that link the human genome to complex psychological syndromes, and to foster breakthroughs in the development of novel treatments for neuropsychiatric disorders. 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Consortium for Neuropsychiatric Phenomics LA5c Study","subjects_count":272,"_subjects_count":272,"accession_number":"ds000030","data_files_count":527,"study_description":"The Consortium for Neuropsychiatric Phenomics (CNP) is a large study funded by the NIH Roadmap Initiative that aims to facilitate discovery of the genetic and environmental bases of variation in psychological and neural system phenotypes, to elucidate the mechanisms that link the human genome to complex psychological syndromes, and to foster breakthroughs in the development of novel treatments for neuropsychiatric disorders. The study includes imaging of a large group of healthy individuals from the community (138 subjects), as well as samples of individuals diagnosed with schizoprenia (58), bipolar disorder (49), and ADHD (45). The participants, ages 21-50, were recruited by community advertisements from the Los Angeles area and completed extensive neuropsychogical testing, in addition to fMRI scanning. To be included individuals had to be either \"White, Not of Hispanic or Latino Origin\" or \"Hispanic or Latino, of Any Race\" following NIH designations of racial and ethnic minority groups, and have completed at least 8 years of education (other racial and ethnic minority groups were excluded because this was thought to increase risk of confounding planned genetic studies). For participants who spoke both English and Spanish, language for testing was determined by a verbal fluency test. Participants were screened for neurological disease, history of head injury with loss of consciousness or cognitive sequelae, use of psychoactive medications, substance dependence within past 6 months, history of major mental illness or ADHD, and current mood or anxiety disorder. Self-reported history of psychopathology was verified with the SCID-IV (First, Spitzer, Gibbon, & Williams, 1995). Urinalysis was used to screen for drugs of abuse (cannabis, amphetamine, opioids, cocaine, benzodiazepines) on the day of testing and excluded if results were positive."}},"GSE63878":{"_guid_type":"discovery_metadata","gen3_discovery":{"link":"https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63878","tags":[{"name":"Array","category":"Data Type"}],"authz":"/programs/GEO/projects/GSE63878","source":"Ichan School of Medicine at Mount Sinai","commons":"Open Access Data Commons","funding":"","summary":"The molecular factors involved in the development of Post-traumatic Stress Disorder (PTSD) remain poorly understood. Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. 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Previous transcriptomic studies investigating the mechanisms of PTSD apply targeted approaches to identify individual genes under a cross-sectional framework lack a holistic view of the behaviours and properties of these genes at the system-level. Here we sought to apply an unsupervised gene-network-based approach to a prospective experimental design using whole-transcriptome RNA-Seq gene expression from peripheral blood leukocytes of U.S. Marines (N=188), obtained both pre- and post-deployment to conflict zones. We identified discrete groups of co-regulated genes (i.e., co-expression modules) and tested them for association to PTSD. We identified one module at both pre- and post-deployment containing putative causal signatures for PTSD development displaying an over-expression of genes enriched for functions of innate-immune response and interferon signalling (Type-I and Type-II). Importantly, these results were replicated in a second non-overlapping independent dataset of U.S. Marines (N=96), further outlining the role of innate immune and interferon signalling genes within co-expression modules to explain at least part of the causal pathophysiology for PTSD development. A second module, consequential of trauma exposure, contained PTSD resiliency signatures and an over-expression of genes involved in hemostasis and wound responsiveness suggesting that chronic levels of stress impair proper wound healing during/after exposure to the battlefield while highlighting the role of the hemostatic system as a clinical indicator of chronic-based stress. These findings provide novel insights for early preventative measures and advanced PTSD detection, which may lead to interventions that delay or perhaps abrogate the development of PTSD.\nWe used microarrays to characterize both prognostic and diagnostic molecular signatures associated to PTSD risk and PTSD status compared to control subjects."}}}