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A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence

Publication ,  Journal Article
Spain, SL; Pedroso, I; Kadeva, N; Miller, MB; Iacono, WG; McGue, M; Stergiakouli, E; Smith, GD; Putallaz, M; Lubinski, D; Meaburn, EL ...
Published in: Molecular Psychiatry

Although individual differences in intelligence (general cognitive ability) are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. The present study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations. We therefore performed a case-control association analysis with 1 409 individuals drawn from the top 0.0003 (IQ > 170) of the population distribution of intelligence and 3 253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina Human Exome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes. However, analyses using genome-wide similarity between unrelated individuals (Genome-wide Complex Trait Analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (SE 1.7%) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis. This observation is consistent with the hypothesis that rare functional alleles are more frequently detrimental than beneficial to intelligence.

Duke Scholars

Published In

Molecular Psychiatry

ISSN

1476-5578

Publisher

Nature Publishing Group: Open Access Hybrid Model Option B

Related Subject Headings

  • Quantitative Trait, Heritable
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Intelligence
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation
 

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Spain, S. L., Pedroso, I., Kadeva, N., Miller, M. B., Iacono, W. G., McGue, M., … Simpson, M. A. (n.d.). A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence. Molecular Psychiatry.
Spain, S. L., I. Pedroso, N. Kadeva, M. B. Miller, W. G. Iacono, M. McGue, E. Stergiakouli, et al. “A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.” Molecular Psychiatry, n.d.
Spain SL, Pedroso I, Kadeva N, Miller MB, Iacono WG, McGue M, et al. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence. Molecular Psychiatry.
Spain, S. L., et al. “A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence.” Molecular Psychiatry, Nature Publishing Group: Open Access Hybrid Model Option B.
Spain SL, Pedroso I, Kadeva N, Miller MB, Iacono WG, McGue M, Stergiakouli E, Smith GD, Putallaz M, Lubinski D, Meaburn EL, Plomin R, Simpson MA. A genome-wide analysis of putative functional and exonic variation associated with extremely high intelligence. Molecular Psychiatry. Nature Publishing Group: Open Access Hybrid Model Option B;

Published In

Molecular Psychiatry

ISSN

1476-5578

Publisher

Nature Publishing Group: Open Access Hybrid Model Option B

Related Subject Headings

  • Quantitative Trait, Heritable
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Multifactorial Inheritance
  • Male
  • Intelligence
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Variation