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A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability

Molecular Psychiatry volume 9, pages 582–586 (2004)Cite this article

Abstract

Succinate-semialdehyde dehydrogenase (SSADH) deficiency is a rare cause of learning disability. We have investigated SSADH to assess its contribution to cognitive ability in the general population in both case–control- and family-based analyses. Sequence analysis of SSADH revealed four changes affecting the encoded protein, only one of which had a minor allele whose frequency is even moderately common. We genotyped this functional polymorphism in 197 high-IQ cases, 201 average-IQ controls and 196 parent high-IQ offspring trios. The minor allele was significantly less frequent in high-IQ cases and was significantly less frequently transmitted by parents to high-IQ subjects than chance expectation. A previous study has shown that the minor allele encodes a lower activity enzyme than the major allele. These data suggest that higher SSADH activity is associated with higher intelligence across the general population. The effect is small, with each allele having an effect size translating to about 1.5 IQ points.

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Acknowledgements

The research was funded by US National Institute of Child Health and Human Development Grant HD27694. Other researchers who have contributed to the current phase of the IQ QTL Project include Ian W Craig, Shaun Purcell and Pak Sham, King's College London; Nigel M Williams, University of Wales College of Medicine; Lee A Thompson, Case Western Reserve University; and David Lubinski, Vanderbilt University.

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Authors and Affiliations

  1. Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, UK

    R Plomin & L Hill

  2. Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK

    D M Turic, D E Turic, M Stephens, J Williams, M J Owen & M C O'Donovan

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  1. R Plomin
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  2. D M Turic
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  3. L Hill
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  7. M J Owen
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Correspondence to M C O'Donovan.

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Plomin, R., Turic, D., Hill, L. et al. A functional polymorphism in the succinate-semialdehyde dehydrogenase (aldehyde dehydrogenase 5 family, member A1) gene is associated with cognitive ability. Mol Psychiatry 9, 582–586 (2004). https://doi.org/10.1038/sj.mp.4001441

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Keywords

  • succinate-semialdehyde dehydrogenase (SSADH)
  • functional polymorphism
  • QTL
  • cognition
  • intelligence

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