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

Proceedings of the National Academy of Sciences of the United States of America

Authors: Else Eising, Nazanin Mirza-Schreiber, Eveline L de Zeeuw, Carol A Wang, Dongnhu T Truong, Andrea G Allegrini, Chin Yang Shapland, Gu Zhu, Karen G Wigg, Margot L Gerritse, Barbara Molz, Gökberk Alagöz, Alessandro Gialluisi, Filippo Abbondanza, Kaili Rimfeld, Marjolein van Donkelaar, Zhijie Liao, Philip R Jansen, Till F M Andlauer, Timothy C Bates, Manon Bernard, Kirsten Blokland, Milene Bonte, Anders D Børglum, Thomas Bourgeron, Daniel Brandeis, Fabiola Ceroni, Valéria Csépe, Philip S Dale, Peter F de Jong, John C DeFries, Jean-François Démonet, Ditte Demontis, Yu Feng, Scott D Gordon, Sharon L Guger, Marianna E Hayiou-Thomas, Juan A Hernández-Cabrera, Jouke-Jan Hottenga, Charles Hulme, Juha Kere, Elizabeth N Kerr, Tanner Koomar, Karin Landerl, Gabriel T Leonard, Maureen W Lovett, Heikki Lyytinen, Nicholas G Martin, Angela Martinelli, Urs Maurer, Jacob J Michaelson, Kristina Moll, Anthony P Monaco, Angela T Morgan, Markus M Nöthen, Zdenka Pausova, Craig E Pennell, Bruce F Pennington, Kaitlyn M Price, Veera M Rajagopal, Franck Ramus, Louis Richer, Nuala H Simpson, Shelley D Smith, Margaret J Snowling, John Stein, Lisa J Strug, Joel B Talcott, Henning Tiemeier, Marc P van der Schroeff, Ellen Verhoef, Kate E Watkins, Margaret Wilkinson, Margaret J Wright, Cathy L Barr, Dorret I Boomsma, Manuel Carreiras, Marie-Christine J Franken, Jeffrey R Gruen, Michelle Luciano, Bertram Müller-Myhsok, Dianne F Newbury, Richard K Olson, Silvia Paracchini, Tomáš Paus, Robert Plomin, Sheena Reilly, Gerd Schulte-Körne, J Bruce Tomblin, Elsje van Bergen, Andrew J O Whitehouse, Erik G Willcutt, Beate St Pourcain, Clyde Francks, Simon E Fisher

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, = 1.098 × 10) 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.

PMID: 35998220

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