Genome-wide screening for DNA variants associated with reading and language traits

A. Gialluisi; D.F. Newbury; E.G. Wilcutt; R.K. Olson; J.C. DeFries; W.M. Brandler; B.F. Pennington; S.D. Smith; T.S. Scerri; N.H. Simpson; M. Luciano; D.M. Evans; T.C. Bates; J.F. Stein; J.B. Talcott; A.P. Monaco; S. Paracchini; C. Francks; S.E. Fisher

doi:10.1111/gbb.12158

Genome-wide screening for DNA variants associated with reading and language traits

A. Gialluisi, D.F. Newbury, E.G. Wilcutt, R.K. Olson, J.C. DeFries, W.M. Brandler, B.F. Pennington, S.D. Smith, T.S. Scerri, N.H. Simpson, , M. Luciano, D.M. Evans, T.C. Bates, J.F. Stein, J.B. Talcott, A.P. Monaco, S. Paracchini, C. Francks, S.E. Fisher

Research output: Contribution to journal › Article › peer-review

Abstract

Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P≈10 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills. Genome-wide association scan meta-analysis for reading and language ability.

Original language	English
Pages (from-to)	686–701
Number of pages	16
Journal	Genes, Brain and Behavior
Volume	13
Issue number	7
Early online date	29 Aug 2014
DOIs	https://doi.org/10.1111/gbb.12158
Publication status	Published - Sept 2014

Bibliographical note

© 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Funding: Max Planck Society, the University of St Andrews, the EU (Neurodys, 018696), and the US National Institutes of Health (Grant ref: P50 HD027802). Genotyping at the Wellcome Trust Centre for Human Genetics was supported by the Wellcome Trust (090532/Z/09/Z) and a Medical Research Council Hub Grant (G0900747 91070). UK Medical Research Council and the Wellcome Trust (Grant ref: 092731).

Keywords

pleiotropic variants
CLDRC
developmental dyslexia
GWAS
language
meta-analysis
reading
reading disability
SLIC
specific language impairment

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10.1111/gbb.12158Licence: CC BY 3.0

Genome-wide screening for DNA variants associated with reading and language traits
© 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 968 KBLicence: CC BY 3.0

Cite this

Gialluisi, A., Newbury, D. F., Wilcutt, E. G., Olson, R. K., DeFries, J. C., Brandler, W. M., Pennington, B. F., Smith, S. D., Scerri, T. S., Simpson, N. H., Luciano, M., Evans, D. M., Bates, T. C., Stein, J. F., Talcott, J. B., Monaco, A. P., Paracchini, S., & Francks, C., & Fisher, S. E. (2014). Genome-wide screening for DNA variants associated with reading and language traits. Genes, Brain and Behavior, 13(7), 686–701. https://doi.org/10.1111/gbb.12158

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title = "Genome-wide screening for DNA variants associated with reading and language traits",

abstract = "Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P≈10 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills. Genome-wide association scan meta-analysis for reading and language ability.",

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author = "A. Gialluisi and D.F. Newbury and E.G. Wilcutt and R.K. Olson and J.C. DeFries and W.M. Brandler and B.F. Pennington and S.D. Smith and T.S. Scerri and N.H. Simpson and M. Luciano and D.M. Evans and T.C. Bates and J.F. Stein and J.B. Talcott and A.P. Monaco and S. Paracchini and C. Francks and S.E. Fisher",

note = "{\textcopyright} 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Max Planck Society, the University of St Andrews, the EU (Neurodys, 018696), and the US National Institutes of Health (Grant ref: P50 HD027802). Genotyping at the Wellcome Trust Centre for Human Genetics was supported by the Wellcome Trust (090532/Z/09/Z) and a Medical Research Council Hub Grant (G0900747 91070). UK Medical Research Council and the Wellcome Trust (Grant ref: 092731).",

year = "2014",

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Gialluisi, A, Newbury, DF, Wilcutt, EG, Olson, RK, DeFries, JC, Brandler, WM, Pennington, BF, Smith, SD, Scerri, TS, Simpson, NH, Luciano, M, Evans, DM, Bates, TC, Stein, JF, Talcott, JB, Monaco, AP, Paracchini, S & Francks, C & Fisher, SE 2014, 'Genome-wide screening for DNA variants associated with reading and language traits', Genes, Brain and Behavior, vol. 13, no. 7, pp. 686–701. https://doi.org/10.1111/gbb.12158

TY - JOUR

T1 - Genome-wide screening for DNA variants associated with reading and language traits

AU - Gialluisi, A.

AU - Newbury, D.F.

AU - Wilcutt, E.G.

AU - Olson, R.K.

AU - DeFries, J.C.

AU - Brandler, W.M.

AU - Pennington, B.F.

AU - Smith, S.D.

AU - Scerri, T.S.

AU - Simpson, N.H.

AU - Luciano, M.

AU - Evans, D.M.

AU - Bates, T.C.

AU - Stein, J.F.

AU - Talcott, J.B.

AU - Monaco, A.P.

AU - Paracchini, S.

AU - Francks, C.

AU - Fisher, S.E.

N1 - © 2014 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Max Planck Society, the University of St Andrews, the EU (Neurodys, 018696), and the US National Institutes of Health (Grant ref: P50 HD027802). Genotyping at the Wellcome Trust Centre for Human Genetics was supported by the Wellcome Trust (090532/Z/09/Z) and a Medical Research Council Hub Grant (G0900747 91070). UK Medical Research Council and the Wellcome Trust (Grant ref: 092731).

PY - 2014/9

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N2 - Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P≈10 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills. Genome-wide association scan meta-analysis for reading and language ability.

AB - Reading and language abilities are heritable traits that are likely to share some genetic influences with each other. To identify pleiotropic genetic variants affecting these traits, we first performed a genome-wide association scan (GWAS) meta-analysis using three richly characterized datasets comprising individuals with histories of reading or language problems, and their siblings. GWAS was performed in a total of 1862 participants using the first principal component computed from several quantitative measures of reading- and language-related abilities, both before and after adjustment for performance IQ. We identified novel suggestive associations at the SNPs rs59197085 and rs5995177 (uncorrected P≈10 for each SNP), located respectively at the CCDC136/FLNC and RBFOX2 genes. Each of these SNPs then showed evidence for effects across multiple reading and language traits in univariate association testing against the individual traits. FLNC encodes a structural protein involved in cytoskeleton remodelling, while RBFOX2 is an important regulator of alternative splicing in neurons. The CCDC136/FLNC locus showed association with a comparable reading/language measure in an independent sample of 6434 participants from the general population, although involving distinct alleles of the associated SNP. Our datasets will form an important part of on-going international efforts to identify genes contributing to reading and language skills. Genome-wide association scan meta-analysis for reading and language ability.

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KW - developmental dyslexia

KW - GWAS

KW - language

KW - meta-analysis

KW - reading

KW - reading disability

KW - SLIC

KW - specific language impairment

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UR - http://onlinelibrary.wiley.com/doi/10.1111/gbb.12158/abstract

U2 - 10.1111/gbb.12158

DO - 10.1111/gbb.12158

M3 - Article

SN - 1601-1848

VL - 13

SP - 686

EP - 701

JO - Genes, Brain and Behavior

JF - Genes, Brain and Behavior

IS - 7

ER -

Genome-wide screening for DNA variants associated with reading and language traits

Abstract

Bibliographical note

Keywords

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