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The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts

Molecular Psychiatry volume 11, pages 878–886 (2006)Cite this article

Abstract

The synaptosomal-associated protein of 25 kDa (SNAP-25) gene plays an integral role in synaptic transmission, and is differentially expressed in the mammalian brain in the neocortex, hippocampus, anterior thalamic nuclei, substantia nigra and cerebellar granular cells. Recent studies have suggested a possible involvement of SNAP-25 in learning and memory, both of which are key components of human intelligence. In addition, the SNAP-25 gene lies in a linkage area implicated previously in human intelligence. In two independent family-based Dutch samples of 391 (mean age 12.4 years) and 276 (mean age 37.3 years) subjects, respectively, we genotyped 12 single-nucleotide polymorphisms (SNPs) in the SNAP-25 gene on 20p12–20p11.2. From all individuals, standardized intelligence measures were available. Using a family-based association test, a strong association was found between three SNPs in the SNAP-25 gene and intelligence, two of which showed association in both independent samples. The strongest, replicated association was found between SNP rs363050 and performance IQ (PIQ), where the A allele was associated with an increase of 2.84 PIQ points (P=0.0002). Variance in this SNP accounts for 3.4 % of the phenotypic variance in PIQ.

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Acknowledgements

This study was supported by the Universitair Stimulerings Fonds (Grant no. 96/22), the Human Frontiers of Science Program (Grant no. rg0154/1998-B) and the Netherlands Organization for Scientific Research (NWO) Grants 904-57-94 and NWO/SPI 56-464-14192. DP was supported by GenomEUtwin Grant EU/QLRT-2001-01254 and by NWO/MaGW Vernieuwingsimpuls 016-065-318. This study was supported by the Centre for Medical Systems Biology (CMSB), a centre of excellence approved by the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NWO). We thank Saskia van Mil and David Sondervan from the Medical Genomics Laboratory for technical support, and Zoltan Bochdanovits for valuable comments. We also like to thank the families from the Netherland Twin Registry (NTR) who participated in this study.

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Authors and Affiliations

  1. Department of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands

    M F Gosso, E J C de Geus, T J C Polderman, P Heutink, D I Boomsma & D Posthuma

  2. Department of Clinical Genetics and Anthropogenetics, Section of Medical Genomics, VU Medical Center, Amsterdam, The Netherlands

    M F Gosso, M J van Belzen, P Heutink & D I Boomsma

  3. Center for Neurogenomics and Cognitive Research – CNCR, Vrije Universiteit, Amsterdam, The Netherlands

    M F Gosso, E J C de Geus, M J van Belzen, P Heutink, D I Boomsma & D Posthuma

  4. Department of Child and Adolescent Psychiatry, Erasmus University, Rotterdam, The Netherlands

    T J C Polderman

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Correspondence to M F Gosso.

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Gosso, M., de Geus, E., van Belzen, M. et al. The SNAP-25 gene is associated with cognitive ability: evidence from a family-based study in two independent Dutch cohorts. Mol Psychiatry 11, 878–886 (2006). https://doi.org/10.1038/sj.mp.4001868

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