Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Lam, M., Chen, C., Ge, T., Xia, Y., Hill, D. W., Trampush, J. W., Yu, J., Knowles, E., Davies, G., Stahl, E. A., Huckins, L., Liewald, D. C., Djurovic, S., Melle, I., Christoforou, A., Reinvang, I., DeRosse, P., Lundervold, A. J., Steen, V. M., Espeseth, T., Räikkönen, K., Widen, E., Palotie, A., Eriksson, J. G., Giegling, I., Konte, B., Hartmann, A. M., Roussos, P., Giakoumaki, S., Burdick, K. E., Payton, A., Ollier, W., Chiba-Falek, O., Koltai, D. C., Need, A. C., Cirulli, E. T., Voineskos, A. N., Stefanis, N. C., Avramopoulos, D., Hatzimanolis, A., Smyrnis, N., Bilder, R. M., Freimer, N. B., Cannon, T. D., London, E., Poldrack, R. A., Sabb, F. W., Congdon, E., Conley, E. D., Scult, M. A., Dickinson, D., Straub, R. E., Donohoe, G., Morris, D., Corvin, A., Gill, M., Hariri, A. R., Weinberger, D. R., Pendleton, N., Bitsios, P., Rujescu, D., Lahti, J., Le Hellard, S., Keller, M. C., Andreassen, O. A., Deary, I. J., Glahn, D. C., Huang, H., Liu, C., Malhotra, A. K., & Lencz, T. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 46(10):1788–1801, September, 2021.
Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. [link]Paper  doi  abstract   bibtex   
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.
@article{lam_identifying_2021,
	title = {Identifying nootropic drug targets via large-scale cognitive {GWAS} and transcriptomics.},
	volume = {46},
	issn = {0893-133X},
	url = {https://escholarship.org/uc/item/338966jd},
	doi = {10.1038/s41386-021-01023-4},
	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.},
	language = {en},
	number = {10},
	urldate = {2022-06-28},
	journal = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology},
	author = {Lam, Max and Chen, Chia-Yen and Ge, Tian and Xia, Yan and Hill, David W. and Trampush, Joey W. and Yu, Jin and Knowles, Emma and Davies, Gail and Stahl, Eli A. and Huckins, Laura and Liewald, David C. and Djurovic, Srdjan and Melle, Ingrid and Christoforou, Andrea and Reinvang, Ivar and DeRosse, Pamela and Lundervold, Astri J. and Steen, Vidar M. and Espeseth, Thomas and Räikkönen, Katri and Widen, Elisabeth and Palotie, Aarno and Eriksson, Johan G. and Giegling, Ina and Konte, Bettina and Hartmann, Annette M. and Roussos, Panos and Giakoumaki, Stella and Burdick, Katherine E. and Payton, Antony and Ollier, William and Chiba-Falek, Ornit and Koltai, Deborah C. and Need, Anna C. and Cirulli, Elizabeth T. and Voineskos, Aristotle N. and Stefanis, Nikos C. and Avramopoulos, Dimitrios and Hatzimanolis, Alex and Smyrnis, Nikolaos and Bilder, Robert M. and Freimer, Nelson B. and Cannon, Tyrone D. and London, Edythe and Poldrack, Russell A. and Sabb, Fred W. and Congdon, Eliza and Conley, Emily Drabant and Scult, Matthew A. and Dickinson, Dwight and Straub, Richard E. and Donohoe, Gary and Morris, Derek and Corvin, Aiden and Gill, Michael and Hariri, Ahmad R. and Weinberger, Daniel R. and Pendleton, Neil and Bitsios, Panos and Rujescu, Dan and Lahti, Jari and Le Hellard, Stephanie and Keller, Matthew C. and Andreassen, Ole A. and Deary, Ian J. and Glahn, David C. and Huang, Hailiang and Liu, Chunyu and Malhotra, Anil K. and Lencz, Todd},
	month = sep,
	year = {2021},
	pages = {1788--1801},
}

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