دورية أكاديمية
omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases.
العنوان: | omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases. |
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المؤلفون: | Alvarado CX; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA., Makarious MB; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; UCL Movement Disorders Centre, University College London, London WC1N 3BG, UK., Weller CA; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA., Vitale D; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA., Koretsky MJ; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA., Bandres-Ciga S; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA., Iwaki H; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA., Levine K; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA., Singleton A; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA., Faghri F; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA., Nalls MA; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA., Leonard HL; Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20814, USA; Data Tecnica LLC, Washington, DC 20037, USA; Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD 20814, USA; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany. Electronic address: hampton@datatecnica.com. |
المصدر: | American journal of human genetics [Am J Hum Genet] 2024 Jan 04; Vol. 111 (1), pp. 150-164. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 0370475 Publication Model: Print Cited Medium: Internet ISSN: 1537-6605 (Electronic) Linking ISSN: 00029297 NLM ISO Abbreviation: Am J Hum Genet Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 2008- : [Cambridge, MA] : Cell Press Original Publication: Baltimore, American Society of Human Genetics. |
مواضيع طبية MeSH: | Alzheimer Disease*/drug therapy , Alzheimer Disease*/genetics , Neurodegenerative Diseases*/drug therapy , Neurodegenerative Diseases*/genetics , Parkinson Disease*, Humans ; Community Resources ; Multiomics ; Mendelian Randomization Analysis |
مستخلص: | Treatments for neurodegenerative disorders remain rare, but recent FDA approvals, such as lecanemab and aducanumab for Alzheimer disease (MIM: 607822), highlight the importance of the underlying biological mechanisms in driving discovery and creating disease modifying therapies. The global population is aging, driving an urgent need for therapeutics that stop disease progression and eliminate symptoms. In this study, we create an open framework and resource for evidence-based identification of therapeutic targets for neurodegenerative disease. We use summary-data-based Mendelian randomization to identify genetic targets for drug discovery and repurposing. In parallel, we provide mechanistic insights into disease processes and potential network-level consequences of gene-based therapeutics. We identify 116 Alzheimer disease, 3 amyotrophic lateral sclerosis (MIM: 105400), 5 Lewy body dementia (MIM: 127750), 46 Parkinson disease (MIM: 605909), and 9 progressive supranuclear palsy (MIM: 601104) target genes passing multiple test corrections (p Competing Interests: Declaration of interests C.X.A., D.V., K.L., H.L.L., F.F., and M.A.N. declare that they are consultants employed by Data Tecnica International, whose participation in this is part of a consulting agreement between the US National Institutes of Health and said company. M.A.N. is also an advisor to Neuron23, Inc. and Character Biosciences. (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.) |
التعليقات: | Update of: medRxiv. 2023 Jul 14:2023.04.06.23288266. doi: 10.1101/2023.04.06.23288266. (PMID: 37090611) |
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معلومات مُعتمدة: | Z01 AG000949 United States ImNIH Intramural NIH HHS; ZIA AG000534 United States ImNIH Intramural NIH HHS; ZIA NS003154 United States ImNIH Intramural NIH HHS |
فهرسة مساهمة: | Keywords: SMR; druggability; neurodegeneration; summary-data-based Mendelian randomization |
تواريخ الأحداث: | Date Created: 20240105 Date Completed: 20240112 Latest Revision: 20240725 |
رمز التحديث: | 20240726 |
مُعرف محوري في PubMed: | PMC10806756 |
DOI: | 10.1016/j.ajhg.2023.12.006 |
PMID: | 38181731 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1537-6605 |
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DOI: | 10.1016/j.ajhg.2023.12.006 |