Article

 

Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. Public Deposited

https://scholar.colorado.edu/concern/articles/0z708x30b
Abstract
  • Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.
Creator
Date Issued
  • 2017-11-28
Academic Affiliation
Journal Title
Journal Issue/Number
  • 9
Journal Volume
  • 21
File Extent
  • 2597-2613
Subject
Last Modified
  • 2019-12-05
Identifier
  • PubMed ID: 29186694
Resource Type
Rights Statement
DOI
ISSN
  • 2211-1247
Language
License

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