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 30-80%, 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 5-26 years. We identified genome-wide significant association with word reading (rs11208009, p=1.098 x 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 13-26% of trait variability. Genomic structural equation modelling revealed a shared genetic factor explaining most 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 of multivariate GWAS results with neuroimaging traits identified association with the surface area of the banks of the left superior temporal sulcus, a brain region linked to 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 new avenues for deciphering the biological underpinnings of uniquely human traits.
Eising, ElseMirza-Schreiber, Nazaninde Zeeuw, Eveline L.Wang, Carol A.Truong, Dongnhu T.Allegrini, Andrea G.Shapland, Chin YangZhu GuWigg, Karen G.Gerritse, MargotMolz, BarbaraAlagöz, GökberkGialluisi, AlessandroAbbondanza, FilippoRimfeld, Kailivan Donkelaar, MarjoleinLiao ZhijieJansen, Philip R.Andlauer, Till F.M.Bates, Timothy C.Bernard, ManonBlokland, KirstenBonte, MileneBørglum Anders D.Bourgeron, ThomasBrandeis, DanielCeroni, Fabiola Csépe, ValeriaDale, Philip S.de Jong, Peter F.DeFries, John C.Demontis, DitteFeng YuGordon, Scott D.Guger, Sharon L.Hayiou-Thomas, Marianna E.Hernández-Cabrera, Juan A.Hottenga, Jouke-JanHulme, CharlesKere, JuhaKerr, Elizabeth N.Koomar, TannerLanderl, KarinLeonard, GabrielLovett, Maureen W.Lyytinen, HeikkiMartin, Nicholas G.Martinelli, AngelaMaurer, UrsMichaelson, Jacob J.Moll, KristinaMonaco, Anthnony P.Morgan, Angela T.Noethen, Markus M.Pausova, ZdenkaPennell, Craig E.Pennington, Bruce F.Price, Kaitlyn M.Rajagopal, Veera M.Ramus, FranckRicher, LouisSimpson, Nuala H.Smith, ShelleySnowling, Margaret J.Stein, JohnStrug, Lisa J.Talcott, Joel B.Tiemeier, Henningvan der Schroeff, Marc M.P.Verhoef, EllenWatkins, Kate E.Wilkinson, MargaretWright, Margaret J.Barr, Cathy L.Boomsma, Dorret I.Carreiras, ManuelFranken, Marie-Christine J.Gruen, Jeffrey R.Luciano, MichelleMüller-Myhsok, BertramNewbury, Dianne F. Olson, Richard K.Paracchini, SilviaPaus, TomasPlomin, RobertReilly, SheenaSchulte-Körne, GerdTomblin, Brucevan Bergen, ElsjeWhitehouse, Andrew J.O.Willcutt, Erik G.St Pourcain, BeateFrancks, ClydeFisher, Simon E.
Department of Biological and Medical Sciences
Year of publication: 2022Date of RADAR deposit: 2022-07-21