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SPOCK3, a risk gene for adult ADHD and personality disorders

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) is the most frequent psychiatric disorder in children, where it displays a global prevalence of 5 %. In up to 50 % of the cases, ADHD may persist into adulthood (aADHD), where it is often comorbid with personality disorders. Due to a potentially heritable nature of this comorbidity, we hypothesized that their genetic framework may contain common risk-modifying genes. SPOCK3, a poorly characterized, putatively Ca(2+)-binding extracellular heparan/chondroitin sulfate proteoglycan gene encoded by the human chromosomal region 4q32.3, was found to be associated with polymorphisms among the top ranks in a genome-wide association study (GWAS) on ADHD and a pooled GWAS on personality disorder (PD). We therefore genotyped 48 single nucleotide polymorphisms (SNPs) representative of the SPOCK3 gene region in 1,790 individuals (n aADHD = 624, n PD = 630, n controls = 536). In this analysis, we found two SNPs to be nominally associated with aADHD (rs7689440, rs897511) and four PD-associated SNPs (rs7689440, rs897511, rs17052671 and rs1485318); the latter even reached marginal significance after rigorous Bonferroni correction. Bioinformatics tools predicted a possible influence of rs1485318 on transcription factor binding, whereas the other candidate SNPs may have effects on alternative splicing. Our results suggest that SPOCK3 may modify the genetic risk for ADHD and PD; further studies are, however, needed to identify the underlying mechanisms.

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Acknowledgments

We are grateful to all patients for their participation in the study. This study was supported by the DFG (Grant RE1632/5-1 to AR, KFO 125 to AR and KPL; SFB TRR 58 Z02 to AR), BMBF (BMBF 01GV0605 to KPL), IZKF-Wuerzburg (Z-6, to HW and CS). We thank M. Zimmer for his kind help in operating the mass spectrometer. T. Töpner, N. Steigerwald, C. Gagel and J. Auer are credited for excellent technical assistance.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Heike Weber, Christian P. Jacob, Julia Heupel, Sarah Kittel-Schneider, Susanne Hempel, Brigitte Schmidt, Tilman Kiel, Alexandra Gessner, Klaus-Peter Lesch & Andreas Reif

  2. Microarray and NGS Unit, Interdisciplinary Center for Clinical Research (IZKF), University Hospital of Würzburg, Würzburg, Germany

    Heike Weber & Claus-Jürgen Scholz

  3. Max-Planck-Institute of Psychiatry, Munich, Germany

    Christian P. Jacob & Angelika Erhardt

  4. ADHD Clinical Research Unit, Division of Molecular Psychiatry, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Julia Heupel, Klaus-Peter Lesch & Andreas Reif

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Weber, H., Scholz, CJ., Jacob, C.P. et al. SPOCK3, a risk gene for adult ADHD and personality disorders. Eur Arch Psychiatry Clin Neurosci 264, 409–421 (2014). https://doi.org/10.1007/s00406-013-0476-2

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