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

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 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 x 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 x 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
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 - Feb 2011

Keywords

Quantitative-trait locus
Genome-wide association
Relative hand skill
Developmental dyslexia
Susceptibility gene
REading-disability
Linkage analysis
Chromosome 6P
United States
Language

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10.1093/hmg/ddq475

HumMolGenet-2011-Scerri-608-14
© 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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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 x 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 x 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.",

keywords = "Quantitative-trait locus, Genome-wide association, Relative hand skill, Developmental dyslexia, Susceptibility gene, REading-disability, Linkage analysis, Chromosome 6P, United States, Language",

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 John Stein and Monaco, {Anthony P.}",

year = "2011",

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doi = "10.1093/hmg/ddq475",

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T1 - PCSK6 is associated with handedness in individuals with dyslexia

AU - Scerri, Thomas S.

AU - Brandler, William M.

AU - Paracchini, Silvia

AU - Morris, Andrew P.

AU - Ring, Susan M.

AU - Richardson, Alex J.

AU - Talcott, Joel B.

AU - Stein, John

AU - Monaco, Anthony P.

PY - 2011/2

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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 x 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 x 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.

AB - 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 x 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 x 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.

KW - Quantitative-trait locus

KW - Genome-wide association

KW - Relative hand skill

KW - Developmental dyslexia

KW - Susceptibility gene

KW - REading-disability

KW - Linkage analysis

KW - Chromosome 6P

KW - United States

KW - Language

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DO - 10.1093/hmg/ddq475

M3 - Article

SN - 0964-6906

VL - 20

SP - 608

EP - 614

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 3

ER -

PCSK6 is associated with handedness in individuals with dyslexia

Abstract

Keywords

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