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8 results on '"Million Veteran Program"'

1. 27. GENOME-WIDE CROSS-DISORDER ANALYSES OF ADHD AND CANNABIS USE DISORDER AND CANNABIS USE

Author

Trine Tollerup Nielsen, Daniel Levey, G. Bragi Walters, Jakob Grove, Emma Johnson, Thorgeir Thorgeirsson, null Million Veteran Program (MVP), Murray Stein, Arpana Agrawal, Hreinn Stefansson, Kari Stefansson, Joel Gelernter, David M. Hougaard, Anders D. Børglum, and Ditte Demontis

Subjects
Pharmacology, Psychiatry and Mental health, Neurology, Pharmacology (medical), Neurology (clinical), Biological Psychiatry
Published
2022

2. Genotyping Array Design and Data Quality Control in the Million Veteran Program

Author

John Concato, Timothy J. O'Leary, Mary Brophy, Lakshmi Radhakrishnan, Jie Huang, Purushotham Karnam, VA Million Veteran Program, Sun-Gou Ji, Haley Hunter-Zinck, Saiju Pyarajan, Man Li, Yunling Shi, Xin Gong, Jennifer Moser, Ronald M. Przygodzki, Philip S. Tsao, Elizabeth R. Hauser, Sumitra Muralidhar, Joel Gelernter, Paul Hsieh, John Michael Gaziano, Ning Sun, Poornima Devineni, Donald E. Humphries, Christopher J. O'Donnell, Hongyu Zhao, Teresa Webster, Themistocles L. Assimes, Grant D. Huang, Jeanette Schmidt, Andrew Liem, Cuiping Pan, and Bryan R Gorman

Subjects
Genetic Markers, Male, Quality Control, 0301 basic medicine, Genotype, Genetic genealogy, Genome-wide association study, Polymorphism, Single Nucleotide, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Ethnicity, Genetics, Humans, Medicine, Precision Medicine, Veterans Affairs, Genotyping, Genetics (clinical), Aged, Veterans, Aged, 80 and over, Whole Genome Sequencing, business.industry, Middle Aged, Precision medicine, Biobank, 030104 developmental biology, Data quality, Cohort, Female, business, 030217 neurology & neurosurgery, Genome-Wide Association Study, Demography
Abstract

The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availability of extensive VA electronic health records, make it a promising resource for precision medicine. MVP is conducting array-based genotyping to provide a genome-wide scan of the entire cohort, in parallel with whole-genome sequencing, methylation, and other ‘omics assays. Here, we present the design and performance of the MVP 1.0 custom Axiom array, which was designed and developed as a single assay to be used across the multi-ethnic MVP cohort. A unified genetic quality-control analysis was developed and conducted on an initial tranche of 485,856 individuals, leading to a high-quality dataset of 459,777 unique individuals. 668,418 genetic markers passed quality control and showed high-quality genotypes not only on common variants but also on rare variants. We confirmed that, with non-European individuals making up nearly 30%, MVP’s substantial ancestral diversity surpasses that of other large biobanks. We also demonstrated the quality of the MVP dataset by replicating established genetic associations with height in European Americans and African Americans ancestries. This current dataset has been made available to approved MVP researchers for genome-wide association studies and other downstream analyses. Further data releases will be available for analysis as recruitment at the VA continues and the cohort expands both in size and diversity.

Published
2020

3. Omega-3 supplement use, fish intake, and risk of non-fatal coronary artery disease and ischemic stroke in the Million Veteran Program

Author

Yuk-Lam Ho, Peter W.F. Wilson, VA Million Veteran Program, Kelly Cho, David R. Gagnon, Xuan-Mai T. Nguyen, Jason L. Vassy, Rachel Quaden, Luc Djoussé, J. Michael Gaziano, and Rachel E. Ward

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Population, 030209 endocrinology & metabolism, Coronary Artery Disease, Critical Care and Intensive Care Medicine, Lower risk, Risk Assessment, Article, law.invention, Cohort Studies, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Surveys and Questionnaires, Internal medicine, Fatty Acids, Omega-3, medicine, Humans, Longitudinal Studies, Prospective Studies, education, Stroke, Aged, Ischemic Stroke, Veterans, education.field_of_study, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Hazard ratio, medicine.disease, United States, Confidence interval, Diet, Seafood, Dietary Supplements, Female, Self Report, business, Body mass index
Abstract

BACKGROUND AND AIMS: Observational and clinical trial evidence suggests an inverse association of omega-3 polyunsaturated fatty acid with coronary artery disease (CAD) mortality, although relationships with non-fatal CAD and stroke are less clear. We investigated whether omega-3 fatty acid supplement use and fish intake were associated with incident non-fatal CAD and ischemic stroke among US Veterans. METHODS: The Million Veteran Program (MVP) is an ongoing nation-wide longitudinal cohort study of US Veterans with self-reported survey, biospecimen, and electronic health record data. Regular use of omega-3 supplements (yes/no) and frequency of fish intake within the past year were assessed using a food frequency questionnaire. Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the associations of omega-3 supplement use and fish intake with incident non-fatal CAD and ischemic stroke, defined from electronic health records using validated algorithms. Multivariable models included demographics, body mass index, education, smoking status, alcohol intake, and exercise frequency. RESULTS: Among 197,761 participants with food frequency data (mean age: 66 ± 12 years, 92% men), 21% regularly took omega-3 supplements and median fish intake was 1 (3–5 ounce) serving/week. Over a median follow-up of 2.9 years for non-fatal CAD and 3.3 years for non-fatal ischemic stroke, we observed 6,265 and 4,042 incident cases of non-fatal CAD and non-fatal ischemic stroke, respectively. Omega-3 fatty acid supplement use was independently associated with a lower risk of non-fatal ischemic stroke [HR (95% CI): 0.88 (0.81, 0.95)] but not non-fatal CAD [0.99 (0.93, 1.06)]. Fish intake was not independently associated with non-fatal CAD [1.01 (0.94, 1.09) for 1–3 servings/month, 1.03 (0.98, 1.11) for 1 serving/week, 1.02 (0.93, 1.11) for 2–4 servings/week, and 1.15 (0.98, 1.35) for ≥5 servings/week, reference =

Published
2020

4. Penetrance and Pleiotropy of Polygenic Risk Scores for Schizophrenia, Bipolar Disorder, and Depression in the VA Health Care System

Author

Tim B. Bigdeli, Georgios Voloudakis, Peter B. Barr, Bryan Gorman, Giulio Genovese, Roseann E. Peterson, David E. Burstein, Vlad I. Velicu, Yuli Li, Rishab Gupta, Manuel Mattheisen, Simone Tomasi, Nallakkandi Rajeevan, Frederick Sayward, Krishnan Radhakrishnan, Sundar Natarajan, Anil K. Malhotra, Yunling Shi, Hongyu Zhao, Thomas R. Kosten, John Concato, Timothy J. O’Leary, Ronald Przygodzki, Theresa Gleason, Saiju Pyarajan, Mary Brophy, Million Veteran Program (MVP), Larry J. Siever, Grant D. Huang, Sumitra Muralidhar, J. Michael Gaziano, Mihaela Aslan, Ayman H. Fanous, Philip D. Harvey, and Panos Rousos

Published
2022

7. The Polygenic and Monogenic Basis of Blood Traits and Diseases

Author

Vuckovic, Dragana, Bao, Erik L, Akbari, Parsa, Lareau, Caleb A, Mousas, Abdou, Jiang, Tao, Chen, Ming-Huei, Raffield, Laura M, Tardaguila, Manuel, Huffman, Jennifer E, Ritchie, Scott C, Megy, Karyn, Ponstingl, Hannes, Penkett, Christopher J, Albers, Patrick K, Wigdor, Emilie M, Sakaue, Saori, Moscati, Arden, Manansala, Regina, Lo, Ken Sin, Qian, Huijun, Akiyama, Masato, Bartz, Traci M, Ben-Shlomo, Yoav, Beswick, Andrew, Bork-Jensen, Jette, Bottinger, Erwin P, Brody, Jennifer A, Van Rooij, Frank JA, Chitrala, Kumaraswamy N, Wilson, Peter WF, Choquet, Hélène, Danesh, John, Di Angelantonio, Emanuele, Dimou, Niki, Ding, Jingzhong, Elliott, Paul, Esko, Tõnu, Evans, Michele K, Felix, Stephan B, Floyd, James S, Broer, Linda, Grarup, Niels, Guo, Michael H, Guo, Qi, Greinacher, Andreas, Haessler, Jeff, Hansen, Torben, Howson, Joanna MM, Huang, Wei, Jorgenson, Eric, Kacprowski, Tim, Kähönen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Karthikeyan, Savita, Koskeridis, Fotios, Lange, Leslie A, Lehtimäki, Terho, Linneberg, Allan, Liu, Yongmei, Lyytikäinen, Leo-Pekka, Manichaikul, Ani, Matsuda, Koichi, Mohlke, Karen L, Mononen, Nina, Murakami, Yoshinori, Nadkarni, Girish N, Nikus, Kjell, Pankratz, Nathan, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Raitakari, Olli T, Rich, Stephen S, Rodriguez, Benjamin AT, Rosen, Jonathan D, Rotter, Jerome I, Schubert, Petra, Spracklen, Cassandra N, Surendran, Praveen, Tang, Hua, Tardif, Jean-Claude, Ghanbari, Mohsen, Völker, Uwe, Völzke, Henry, Watkins, Nicholas A, Weiss, Stefan, VA Million Veteran Program, Cai, Na, Kundu, Kousik, Watt, Stephen B, Walter, Klaudia, Zonderman, Alan B, Cho, Kelly, Li, Yun, Loos, Ruth JF, Knight, Julian C, Georges, Michel, Stegle, Oliver, Evangelou, Evangelos, Okada, Yukinori, Roberts, David J, Inouye, Michael, Johnson, Andrew D, Auer, Paul L, Astle, William J, Reiner, Alexander P, Butterworth, Adam S, Ouwehand, Willem H, Lettre, Guillaume, Sankaran, Vijay G, Soranzo, Nicole, Ritchie, Scott [0000-0002-8454-9548], Megy, Karyn [0000-0002-2826-3879], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Kundu, Kousik [0000-0002-1019-8351], Inouye, Michael [0000-0001-9413-6520], Astle, William [0000-0001-8866-6672], Butterworth, Adam [0000-0002-6915-9015], Ouwehand, Willem [0000-0002-7744-1790], Soranzo, Nicole [0000-0003-1095-3852], and Apollo - University of Cambridge Repository

Subjects
Male, UK Biobank, Multifactorial Inheritance, polygenic risk, rare disease, Polymorphism, Single Nucleotide, hematopoiesis, splicing, Phenotype, fine-mapping, blood, chromatin, Humans, genetics, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, omnigenic, Genome-Wide Association Study
Abstract

Blood cells play essential roles in human health, underpinning physiological processes such as immunity, oxygen transport, and clotting, which when perturbed cause a significant global health burden. Here we integrate data from UK Biobank and a large-scale international collaborative effort, including data for 563,085 European ancestry participants, and discover 5,106 new genetic variants independently associated with 29 blood cell phenotypes covering a range of variation impacting hematopoiesis. We holistically characterize the genetic architecture of hematopoiesis, assess the relevance of the omnigenic model to blood cell phenotypes, delineate relevant hematopoietic cell states influenced by regulatory genetic variants and gene networks, identify novel splice-altering variants mediating the associations, and assess the polygenic prediction potential for blood traits and clinical disorders at the interface of complex and Mendelian genetics. These results show the power of large-scale blood cell trait GWAS to interrogate clinically meaningful variants across a wide allelic spectrum of human variation.

Published
2020
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8. Genomic and Phenomic Correlates of Suicidality Among US Veterans With Schizophrenia or Bipolar Disorder

Author

Saiju Pyarajan, Philip D. Harvey, Mihaela Aslan, Larry J. Siever, John Concato, Frederick G. Sayward, Perry L. Miller, Ayman H. Fanous, David A. Nielsen, Sumitra Muralidhar, Alan C. Swann, David P. Graham, Mary Brophy, Shrikant Mane, Theresa Gleason, Roseann E. Peterson, Yuli Li, Timothy J. O'Leary, Ronald Przygodszki, Kei-Hoi Cheung, J. Michael Gaziano, Anna V. Wilkinson, Million Veteran Program, Nikhil Khankari, Jacquelyn L. Meyers, Tim B. Bigdeli, Thomas R. Kosten, Grant D. Huang, Nallakkandi Rajeevan, and Hongyu Zhao

Subjects
medicine.medical_specialty, business.industry, Schizophrenia, medicine, Bipolar disorder, medicine.disease, Psychiatry, business, Biological Psychiatry
Published
2021

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