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

doi:10.1093/hmg/ddq475

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 journal › Article › peer-review

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 language	English
Article number	ddq475
Pages (from-to)	608-614
Number of pages	7
Journal	Human Molecular Genetics
Volume	20
Issue number	3
DOIs	https://doi.org/10.1093/hmg/ddq475
Publication status	Published - 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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10.1093/hmg/ddq475

PCSK6 is associated with handedness in individuals with dyslexia
© 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.
Final published version, 146 KBLicence: CC BY-NC 3.0

Cite this

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title = "PCSK6 is associated with handedness in individuals with dyslexia",

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.",

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

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AU - Ring, Susan M.

AU - Richardson, Alex J.

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AU - Stein, John F.

AU - Monaco, Anthony P.

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N2 - 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.

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PCSK6 is associated with handedness in individuals with dyslexia

Abstract

Bibliographical note

Keywords

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