The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure

Thomas S Scerri; Fahimeh Darki; Dianne F Newbury; Andrew J O Whitehouse; Myriam Peyrard-Janvid; Hans Matsson; Qi W Ang; Craig E Pennell; Susan Ring; John Stein; Andrew P Morris; Anthony P Monaco; Juha Kere; Joel B Talcott; Torkel Klingberg; Silvia Paracchini

doi:10.1371/journal.pone.0050321

The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure

Thomas S Scerri, Fahimeh Darki, Dianne F Newbury, Andrew J O Whitehouse, Myriam Peyrard-Janvid, Hans Matsson, Qi W Ang, Craig E Pennell, Susan Ring, John Stein, Andrew P Morris, Anthony P Monaco, Juha Kere, Joel B Talcott, Torkel Klingberg, Silvia Paracchini

Bristol Medical School (PHS)

Research output: Contribution to journal › Article (Academic Journal) › peer-review

39 Citations (Scopus)

Abstract

Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.

Original language	English
Pages (from-to)	e50321
Journal	PLoS ONE
Volume	7
Issue number	11
DOIs	https://doi.org/10.1371/journal.pone.0050321
Publication status	Published - 2012

Keywords

Adolescent
Adult
Brain
Brain Mapping
Child
Child, Preschool
Chromosomes, Human, Pair 2
Cognition
Cohort Studies
Diagnostic Imaging
Dyslexia
Female
Genotype
Haplotypes
Humans
Intelligence Tests
Language
Male
Middle Aged
Models, Genetic
Models, Statistical
Neurons
Open Reading Frames
Phenotype
Polymorphism, Single Nucleotide
Risk Factors

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Golding, J. (Principal Investigator)
1/02/01 → 1/02/06
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Scerri, T. S., Darki, F., Newbury, D. F., Whitehouse, A. J. O., Peyrard-Janvid, M., Matsson, H., Ang, Q. W., Pennell, C. E., Ring, S., Stein, J., Morris, A. P., Monaco, A. P., Kere, J., Talcott, J. B., Klingberg, T., & Paracchini, S. (2012). The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure. PLoS ONE, 7(11), e50321. https://doi.org/10.1371/journal.pone.0050321

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title = "The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure",

abstract = "Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.",

keywords = "Adolescent, Adult, Brain, Brain Mapping, Child, Child, Preschool, Chromosomes, Human, Pair 2, Cognition, Cohort Studies, Diagnostic Imaging, Dyslexia, Female, Genotype, Haplotypes, Humans, Intelligence Tests, Language, Male, Middle Aged, Models, Genetic, Models, Statistical, Neurons, Open Reading Frames, Phenotype, Polymorphism, Single Nucleotide, Risk Factors",

author = "Scerri, {Thomas S} and Fahimeh Darki and Newbury, {Dianne F} and Whitehouse, {Andrew J O} and Myriam Peyrard-Janvid and Hans Matsson and Ang, {Qi W} and Pennell, {Craig E} and Susan Ring and John Stein and Morris, {Andrew P} and Monaco, {Anthony P} and Juha Kere and Talcott, {Joel B} and Torkel Klingberg and Silvia Paracchini",

year = "2012",

doi = "10.1371/journal.pone.0050321",

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pages = "e50321",

journal = "PLoS ONE",

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Scerri, TS, Darki, F, Newbury, DF, Whitehouse, AJO, Peyrard-Janvid, M, Matsson, H, Ang, QW, Pennell, CE, Ring, S, Stein, J, Morris, AP, Monaco, AP, Kere, J, Talcott, JB, Klingberg, T & Paracchini, S 2012, 'The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure', PLoS ONE, vol. 7, no. 11, pp. e50321. https://doi.org/10.1371/journal.pone.0050321

TY - JOUR

T1 - The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure

AU - Scerri, Thomas S

AU - Darki, Fahimeh

AU - Newbury, Dianne F

AU - Whitehouse, Andrew J O

AU - Peyrard-Janvid, Myriam

AU - Matsson, Hans

AU - Ang, Qi W

AU - Pennell, Craig E

AU - Ring, Susan

AU - Stein, John

AU - Morris, Andrew P

AU - Monaco, Anthony P

AU - Kere, Juha

AU - Talcott, Joel B

AU - Klingberg, Torkel

AU - Paracchini, Silvia

PY - 2012

Y1 - 2012

N2 - Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.

AB - Independent studies have shown that candidate genes for dyslexia and specific language impairment (SLI) impact upon reading/language-specific traits in the general population. To further explore the effect of disorder-associated genes on cognitive functions, we investigated whether they play a role in broader cognitive traits. We tested a panel of dyslexia and SLI genetic risk factors for association with two measures of general cognitive abilities, or IQ, (verbal and non-verbal) in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N>5,000). Only the MRPL19/C2ORF3 locus showed statistically significant association (minimum P = 0.00009) which was further supported by independent replications following analysis in four other cohorts. In addition, a fifth independent sample showed association between the MRPL19/C2ORF3 locus and white matter structure in the posterior part of the corpus callosum and cingulum, connecting large parts of the cortex in the parietal, occipital and temporal lobes. These findings suggest that this locus, originally identified as being associated with dyslexia, is likely to harbour genetic variants associated with general cognitive abilities by influencing white matter structure in localised neuronal regions.

KW - Adolescent

KW - Adult

KW - Brain

KW - Brain Mapping

KW - Child

KW - Child, Preschool

KW - Chromosomes, Human, Pair 2

KW - Cognition

KW - Cohort Studies

KW - Diagnostic Imaging

KW - Dyslexia

KW - Female

KW - Genotype

KW - Haplotypes

KW - Humans

KW - Intelligence Tests

KW - Language

KW - Male

KW - Middle Aged

KW - Models, Genetic

KW - Models, Statistical

KW - Neurons

KW - Open Reading Frames

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1371/journal.pone.0050321

DO - 10.1371/journal.pone.0050321

M3 - Article (Academic Journal)

C2 - 23209710

SN - 1932-6203

VL - 7

SP - e50321

JO - PLoS ONE

JF - PLoS ONE

IS - 11

ER -

The dyslexia candidate locus on 2p12 is associated with general cognitive ability and white matter structure

Abstract

Keywords

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