Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people


The use of spoken and written language is a fundamental human capacity. Individual differences in reading- and language-related skills are influenced by genetic variation, with twin-based heritability estimates of 30 to 80% depending on the trait. The genetic architecture is complex, heterogeneous, and multifactorial, but investigations of contributions of single-nucleotide polymorphisms (SNPs) were thus far underpowered. We present a multicohort genome-wide association study (GWAS) of five traits assessed individually using psychometric measures (word reading, nonword reading, spelling, phoneme awareness, and nonword repetition) in samples of 13,633 to 33,959 participants aged 5 to 26 y. We identified genome-wide significant association with word reading (rs11208009, P = 1.098 × 10-8) at a locus that has not been associated with intelligence or educational attainment. All five reading-/language-related traits showed robust SNP heritability, accounting for 13 to 26% of trait variability. Genomic structural equation modeling revealed a shared genetic factor explaining most of the variation in word/nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence, and educational attainment. A multivariate GWAS of word/nonword reading, spelling, and phoneme awareness maximized power for follow-up investigation. Genetic correlation analysis with neuroimaging traits identified an association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to the processing of spoken and written language. Heritability was enriched for genomic elements regulating gene expression in the fetal brain and in chromosomal regions that are depleted of Neanderthal variants. Together, these results provide avenues for deciphering the biological underpinnings of uniquely human traits.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > Aston Institute of Health & Neurodevelopment (AIHN)
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
Additional Information: Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Uncontrolled Keywords: genome-wide association study,language,meta-analysis,reading,General
Publication ISSN: 1091-6490
Last Modified: 19 Jun 2024 17:48
Date Deposited: 21 Sep 2022 15:15
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.pna ... pnas.2202764119 (Publisher URL)
PURE Output Type: Article
Published Date: 2022-08-23
Accepted Date: 2022-05-31
Authors: Eising, Else
Mirza-Schreiber, Nazanin
de Zeeuw, Eveline L.
Wang, Carol A.
Truong, Dongnhu T.
Allegrini, Andrea G.
Shapland, Chin Yang
Zhu, Gu
Wigg, Karen G.
Gerritse, Margot L.
Molz, Barbara
Alagöz, Gökberk
Gialluisi, Alessandro
Abbondanza, Filippo
Rimfeld, Kaili
van Donkelaar, Marjolein
Liao, Zhijie
Jansen, Philip R.
Andlauer, Till F.M.
Bates, Timothy C.
Bernard, Manon
Blokland, Kirsten
Bonte, Milene
Børglum, Anders D.
Bourgeron, Thomas
Brandeis, Daniel
Ceroni, Fabiola
Csépe, Valéria
Dale, Philip S.
de Jong, Peter F.
DeFries, John C.
Démonet, Jean François
Demontis, Ditte
Feng, Yu
Gordon, Scott D.
Guger, Sharon L.
Hayiou-Thomas, Marianna E.
Hernández-Cabrera, Juan A.
Hottenga, Jouke Jan
Hulme, Charles
Kere, Juha
Kerr, Elizabeth N.
Koomar, Tanner
Landerl, Karin
Leonard, Gabriel T.
Lovett, Maureen W.
Lyytinen, Heikki
Martin, Nicholas G.
Martinelli, Angela
Maurer, Urs
Michaelson, Jacob J.
Moll, Kristina
Monaco, Anthony P.
Morgan, Angela T.
Nöthen, Markus M.
Pausova, Zdenka
Pennell, Craig E.
Pennington, Bruce F.
Price, Kaitlyn M.
Rajagopal, Veera M.
Ramus, Franck
Richer, Louis
Simpson, Nuala H.
Smith, Shelley D.
Snowling, Margaret J.
Stein, John
Strug, Lisa J.
Talcott, Joel B. (ORCID Profile 0000-0001-7958-8369)
Tiemeier, Henning
van der Schroeff, Marc P.
Verhoef, Ellen
Watkins, Kate E.
Wilkinson, Margaret
Wright, Margaret J.
Barr, Cathy L.
Boomsma, Dorret I.
Carreiras, Manuel
Franken, Marie Christine J.
Gruen, Jeffrey R.
Luciano, Michelle
Müller-Myhsok, Bertram
Newbury, Dianne F.
Olson, Richard K.
Paracchini, Silvia
Paus, Tomáš
Plomin, Robert
Reilly, Sheena
Schulte-Körne, Gerd
Tomblin, J. Bruce
van Bergen, Elsje
Whitehouse, Andrew J.O.
Willcutt, Erik G.
St Pourcain, Beate
Francks, Clyde
Fisher, Simon E.



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License: Creative Commons Attribution

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