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A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.

Publication ,  Journal Article
Need, AC; Attix, DK; McEvoy, JM; Cirulli, ET; Linney, KL; Hunt, P; Ge, D; Heinzen, EL; Maia, JM; Shianna, KV; Weale, ME; Cherkas, LF ...
Published in: Hum Mol Genet
December 1, 2009

Psychiatric disorders such as schizophrenia are commonly accompanied by cognitive impairments that are treatment resistant and crucial to functional outcome. There has been great interest in studying cognitive measures as endophenotypes for psychiatric disorders, with the hope that their genetic basis will be clearer. To investigate this, we performed a genome-wide association study involving 11 cognitive phenotypes from the Cambridge Neuropsychological Test Automated Battery. We showed these measures to be heritable by comparing the correlation in 100 monozygotic and 100 dizygotic twin pairs. The full battery was tested in approximately 750 subjects, and for spatial and verbal recognition memory, we investigated a further 500 individuals to search for smaller genetic effects. We were unable to find any genome-wide significant associations with either SNPs or common copy number variants. Nor could we formally replicate any polymorphism that has been previously associated with cognition, although we found a weak signal of lower than expected P-values for variants in a set of 10 candidate genes. We additionally investigated SNPs in genomic loci that have been shown to harbor rare variants that associate with neuropsychiatric disorders, to see if they showed any suggestion of association when considered as a separate set. Only NRXN1 showed evidence of significant association with cognition. These results suggest that common genetic variation does not strongly influence cognition in healthy subjects and that cognitive measures do not represent a more tractable genetic trait than clinical endpoints such as schizophrenia. We discuss a possible role for rare variation in cognitive genomics.

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Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 1, 2009

Volume

18

Issue

23

Start / End Page

4650 / 4661

Location

England

Related Subject Headings

  • Young Adult
  • Twins
  • Polymorphism, Single Nucleotide
  • Neuropsychological Tests
  • Neural Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study
 

Citation

APA
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Need, A. C., Attix, D. K., McEvoy, J. M., Cirulli, E. T., Linney, K. L., Hunt, P., … Goldstein, D. B. (2009). A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet, 18(23), 4650–4661. https://doi.org/10.1093/hmg/ddp413
Need, Anna C., Deborah K. Attix, Jill M. McEvoy, Elizabeth T. Cirulli, Kristen L. Linney, Priscilla Hunt, Dongliang Ge, et al. “A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.Hum Mol Genet 18, no. 23 (December 1, 2009): 4650–61. https://doi.org/10.1093/hmg/ddp413.
Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, et al. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet. 2009 Dec 1;18(23):4650–61.
Need, Anna C., et al. “A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.Hum Mol Genet, vol. 18, no. 23, Dec. 2009, pp. 4650–61. Pubmed, doi:10.1093/hmg/ddp413.
Need AC, Attix DK, McEvoy JM, Cirulli ET, Linney KL, Hunt P, Ge D, Heinzen EL, Maia JM, Shianna KV, Weale ME, Cherkas LF, Clement G, Spector TD, Gibson G, Goldstein DB. A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB. Hum Mol Genet. 2009 Dec 1;18(23):4650–4661.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

December 1, 2009

Volume

18

Issue

23

Start / End Page

4650 / 4661

Location

England

Related Subject Headings

  • Young Adult
  • Twins
  • Polymorphism, Single Nucleotide
  • Neuropsychological Tests
  • Neural Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Middle Aged
  • Male
  • Humans
  • Genome-Wide Association Study