药物重新定位
全基因组关联研究
认知
重新调整用途
计算生物学
精神分裂症(面向对象编程)
可药性
药品
生物信息学
生物
心理学
基因
精神科
遗传学
单核苷酸多态性
基因型
生态学
作者
Max Lam,Chia‐Yen Chen,Tian Ge,Yan Xia,David W. Hill,Joey W. Trampush,Jin Yu,Emma Knowles,Gail Davies,Eli A. Stahl,Laura M. Huckins,David C. Liewald,Srdjan Djurovic,Ingrid Melle,Andrea Christoforou,Ivar Reinvang,Pamela DeRosse,Astri J. Lundervold,Vidar M. Steen,Thomas Espeseth
标识
DOI:10.1038/s41386-021-01023-4
摘要
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.
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