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

Publication ,  Journal Article
Lam, M; Trampush, JW; Yu, J; Knowles, E; Davies, G; Liewald, DC; Starr, JM; Djurovic, S; Melle, I; Sundet, K; Christoforou, A; Reinvang, I ...
Published in: Cell Rep
November 28, 2017

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.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 28, 2017

Volume

21

Issue

9

Start / End Page

2597 / 2613

Location

United States

Related Subject Headings

  • Synapses
  • Polymorphism, Single Nucleotide
  • Nootropic Agents
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Female
  • Cognition
 

Citation

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Lam, M., Trampush, J. W., Yu, J., Knowles, E., Davies, G., Liewald, D. C., … Lencz, T. (2017). Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. Cell Rep, 21(9), 2597–2613. https://doi.org/10.1016/j.celrep.2017.11.028
Lam, Max, Joey W. Trampush, Jin Yu, Emma Knowles, Gail Davies, David C. Liewald, John M. Starr, et al. “Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.Cell Rep 21, no. 9 (November 28, 2017): 2597–2613. https://doi.org/10.1016/j.celrep.2017.11.028.
Lam M, Trampush JW, Yu J, Knowles E, Davies G, Liewald DC, et al. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. Cell Rep. 2017 Nov 28;21(9):2597–613.
Lam, Max, et al. “Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.Cell Rep, vol. 21, no. 9, Nov. 2017, pp. 2597–613. Pubmed, doi:10.1016/j.celrep.2017.11.028.
Lam M, Trampush JW, Yu J, Knowles E, Davies G, Liewald DC, Starr JM, Djurovic S, Melle I, Sundet K, Christoforou A, Reinvang I, DeRosse P, Lundervold AJ, Steen VM, Espeseth T, Räikkönen K, Widen E, Palotie A, Eriksson JG, Giegling I, Konte B, Roussos P, Giakoumaki S, Burdick KE, Payton A, Ollier W, Chiba-Falek O, Attix DK, Need AC, Cirulli ET, Voineskos AN, Stefanis NC, Avramopoulos D, Hatzimanolis A, Arking DE, Smyrnis N, Bilder RM, Freimer NA, Cannon TD, London E, Poldrack RA, Sabb FW, Congdon E, Conley ED, Scult MA, Dickinson D, Straub RE, Donohoe G, Morris D, Corvin A, Gill M, Hariri AR, Weinberger DR, Pendleton N, Bitsios P, Rujescu D, Lahti J, Le Hellard S, Keller MC, Andreassen OA, Deary IJ, Glahn DC, Malhotra AK, Lencz T. Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets. Cell Rep. 2017 Nov 28;21(9):2597–2613.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

November 28, 2017

Volume

21

Issue

9

Start / End Page

2597 / 2613

Location

United States

Related Subject Headings

  • Synapses
  • Polymorphism, Single Nucleotide
  • Nootropic Agents
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Genetic Loci
  • Female
  • Cognition