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

116 Citations (SciVal)

72 Downloads (Pure)

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.

AU - Talcott, Joel B.

AU - Stein, John F.

AU - Monaco, Anthony P.

N1 - © 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.

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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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ER -

PCSK6 is associated with handedness in individuals with dyslexia

Abstract

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Keywords

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