Journal Article

<i>PCSK6</i> 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 and Anthony P. Monaco

in Human Molecular Genetics

Volume 20, issue 3, pages 608-614
Published in print February 2011 | ISSN: 0964-6906
Published online November 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq475

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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.

Journal Article.  4142 words.  Illustrated.

Subjects: Genetics and Genomics

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