PCSK6 is associated with handedness in individuals with dyslexia


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.

Publication DOI: https://doi.org/10.1093/hmg/ddq475
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
Additional Information: © 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.
Uncontrolled 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,Genetics,Genetics(clinical),Molecular Biology
Publication ISSN: 1460-2083
Last Modified: 11 Jun 2024 07:08
Date Deposited: 07 Feb 2012 12:52
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://hmg.oxfo ... t/20/3/608.full (Publisher URL)
PURE Output Type: Article
Published Date: 2011-02-01
Authors: Scerri, Thomas S.
Brandler, William M.
Paracchini, Silvia
Morris, Andrew P.
Ring, Susan M.
Richardson, Alex J.
Talcott, Joel B. (ORCID Profile 0000-0001-7958-8369)
Stein, John F.
Monaco, Anthony P.


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