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.

Publication DOI: https://doi.org/10.1111/gbb.12158
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Clinical and Systems Neuroscience
College of Health & Life Sciences
College of Health & Life Sciences > School of Optometry > Vision, Hearing and Language
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
Additional Information: © 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).
Uncontrolled Keywords: pleiotropic variants,CLDRC,developmental dyslexia,GWAS,language,meta-analysis,reading,reading disability,SLIC ,specific language impairment
Publication ISSN: 1601-183X
Last Modified: 08 Mar 2024 08:10
Date Deposited: 15 Sep 2014 11:15
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
http://onlineli ... .12158/abstract (Publisher URL)
PURE Output Type: Article
Published Date: 2014-09
Published Online Date: 2014-08-29
Authors: 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.
, SLI Consortium
Luciano, M.
Evans, D.M.
Bates, T.C.
Stein, J.F.
Talcott, J.B. (ORCID Profile 0000-0001-7958-8369)
Monaco, A.P.
Paracchini, S.
Francks, C.
Fisher, S.E.

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