PCSK6 is associated with handedness in individuals with dyslexia

Thomas S. Scerri, William M. Brandler, Silvia Paracchini, Andrew P. Morris, Susan M. Ring, Alex J. Richardson, Joel B. Talcott, John F. Stein, Anthony P. Monaco

Research output: Contribution to journalArticle

Abstract

Approximately 90% of humans are right-handed. Handedness is a heritable trait, yet the genetic basis is not well understood. Here we report a genome-wide association study for a quantitative measure of relative hand skill in individuals with dyslexia [reading disability (RD)]. The most highly associated marker, rs11855415 (P = 4.7 × 10-7), is located within PCSK6. Two independent cohorts with RD show the same trend, with the minor allele conferring greater relative right-hand skill. Meta-analysis of all three RD samples is genome-wide significant (n = 744, P = 2.0 × 10-8). Conversely, in the general population (n = 2666), we observe a trend towards reduced laterality of hand skill for the minor allele (P = 0.0020). These results provide molecular evidence that cerebral asymmetry and dyslexia are linked. Furthermore, PCSK6 is a protease that cleaves the left–right axis determining protein NODAL. Functional studies of PCSK6 promise insights into mechanisms underlying cerebral lateralization and dyslexia.
Original languageEnglish
Article numberddq475
Pages (from-to)608-614
Number of pages7
JournalHuman Molecular Genetics
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Feb 2011

Bibliographical note

© The Author 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

  • handedness
  • genome-wide association
  • hand skill
  • dyslexia
  • rs11855415 (P = 4.7 × 10−7)
  • PCSK6
  • minor allele
  • right-hand skill
  • cerebral asymmetry
  • protein NODAL
  • cerebral lateralization

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    Scerri, T. S., Brandler, W. M., Paracchini, S., Morris, A. P., Ring, S. M., Richardson, A. J., Talcott, J. B., Stein, J. F., & Monaco, A. P. (2011). PCSK6 is associated with handedness in individuals with dyslexia. Human Molecular Genetics, 20(3), 608-614. [ddq475]. https://doi.org/10.1093/hmg/ddq475