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 Stein, Anthony P Monaco

Research output: Contribution to journalArticle (Academic Journal)peer-review

98 Citations (Scopus)

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
Pages (from-to)608-14
Number of pages7
JournalHuman Molecular Genetics
Volume20
Issue number3
DOIs
Publication statusPublished - 1 Feb 2011

Keywords

  • Dominance, Cerebral
  • Dyslexia
  • Functional Laterality
  • Genome-Wide Association Study
  • Humans
  • Nodal Protein

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