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https://doi.org/10.1038/s41386-021-01023-4
Title: | Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics | Authors: | Lam, Max Chen, Chia-Yen Ge, Tian Xia, Yan Hill, David W. Trampush, Joey W. Yu, Jin Knowles, Emma Davies, Gail Stahl, Eli A. Huckins, Laura Liewald, David C. Djurovic, Srdjan Melle, Ingrid Christoforou, Andrea Reinvang, Ivar Derosse, Pamela Lundervold, Astri J. Steen, Vidar M. Espeseth, Thomas Räikkönen, K. Widen, Elisabeth Palotie, Aarno Eriksson, Johan G. Giegling, Ina Konte, Bettina Hartmann, Annette M. Roussos, Panos Giakoumaki, Stella Burdick, Katherine E. Payton, Antony Ollier, William Chiba-Falek, Ornit Koltai, Deborah C. Need, Anna C. Cirulli, Elizabeth T. Voineskos, Aristotle N. Stefanis, Nikos C. Avramopoulos, Dimitrios Hatzimanolis, Alex Smyrnis, Nikolaos Bilder, Robert M. Freimer, Nelson B. Cannon, Tyrone D. London, Edythe Poldrack, Russell A. Sabb, Fred W. Congdon, Eliza Conley, Emily Drabant Scult, Matthew A. Dickinson, Dwight Straub, Richard E. Donohoe, Gary Morris, Derek Corvin, Aiden Gill, Michael Hariri, Ahmad R. Weinberger, Daniel R. Pendleton, Neil Bitsios, Panos Rujescu, Dan Lahti, Jari Le Hellard, S. Keller, Matthew C. Andreassen, Ole A. Deary, Ian J. Glahn, David C. Huang, Hailiang Liu, Chunyu Malhotra, Anil K. Lencz, Todd |
Issue Date: | 25-May-2021 | Publisher: | Springer Nature | Citation: | Lam, Max, Chen, Chia-Yen, Ge, Tian, Xia, Yan, Hill, David W., Trampush, Joey W., Yu, Jin, Knowles, Emma, Davies, Gail, Stahl, Eli A., Huckins, Laura, Liewald, David C., Djurovic, Srdjan, Melle, Ingrid, Christoforou, Andrea, Reinvang, Ivar, Derosse, Pamela, Lundervold, Astri J., Steen, Vidar M., Espeseth, Thomas, Räikkönen, K., Widen, Elisabeth, Palotie, Aarno, Eriksson, Johan G., Giegling, Ina, Konte, Bettina, Hartmann, Annette M., Roussos, Panos, Giakoumaki, Stella, Burdick, Katherine E., Payton, Antony, Ollier, William, Chiba-Falek, Ornit, Koltai, Deborah C., Need, Anna C., Cirulli, Elizabeth T., Voineskos, Aristotle N., Stefanis, Nikos C., Avramopoulos, Dimitrios, Hatzimanolis, Alex, Smyrnis, Nikolaos, Bilder, Robert M., Freimer, Nelson B., Cannon, Tyrone D., London, Edythe, Poldrack, Russell A., Sabb, Fred W., Congdon, Eliza, Conley, Emily Drabant, Scult, Matthew A., Dickinson, Dwight, Straub, Richard E., Donohoe, Gary, Morris, Derek, Corvin, Aiden, Gill, Michael, Hariri, Ahmad R., Weinberger, Daniel R., Pendleton, Neil, Bitsios, Panos, Rujescu, Dan, Lahti, Jari, Le Hellard, S., Keller, Matthew C., Andreassen, Ole A., Deary, Ian J., Glahn, David C., Huang, Hailiang, Liu, Chunyu, Malhotra, Anil K., Lencz, Todd (2021-05-25). Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology 46 (10) : 1788-1801. ScholarBank@NUS Repository. https://doi.org/10.1038/s41386-021-01023-4 | Rights: | Attribution 4.0 International | Abstract: | Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify “druggable” targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing. © 2021, The Author(s). | Source Title: | Neuropsychopharmacology | URI: | https://scholarbank.nus.edu.sg/handle/10635/232912 | ISSN: | 0893-133X | DOI: | 10.1038/s41386-021-01023-4 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications |
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