RT Journal Article
SR Electronic
T1 Genome-wide association analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.04.466897
DO 10.1101/2021.11.04.466897
A1 Else Eising
A1 Nazanin Mirza-Schreiber
A1 Eveline L. de Zeeuw
A1 Carol A. Wang
A1 Dongnhu T. Truong
A1 Andrea G. Allegrini
A1 Chin Yang Shapland
A1 Gu Zhu
A1 Karen G. Wigg
A1 Margot Gerritse
A1 Barbara Molz
A1 Gökberk Alagöz
A1 Alessandro Gialluisi
A1 Filippo Abbondanza
A1 Kaili Rimfeld
A1 Marjolein van Donkelaar
A1 Zhijie Liao
A1 Philip R. Jansen
A1 Till F. M. Andlauer
A1 Timothy C. Bates
A1 Manon Bernard
A1 Kirsten Blokland
A1 Anders D. Børglum
A1 Thomas Bourgeron
A1 Daniel Brandeis
A1 Fabiola Ceroni
A1 Philip S. Dale
A1 Karin Landerl
A1 Heikki Lyytinen
A1 Peter F. de Jong
A1 John C. DeFries
A1 Ditte Demontis
A1 Yu Feng
A1 Scott D. Gordon
A1 Sharon L. Guger
A1 Marianna E. Hayiou-Thomas
A1 Juan A. Hernández-Cabrera
A1 Jouke-Jan Hottenga
A1 Charles Hulme
A1 Elizabeth N. Kerr
A1 Tanner Koomar
A1 Maureen W. Lovett
A1 Nicholas G. Martin
A1 Angela Martinelli
A1 Urs Maurer
A1 Jacob J. Michaelson
A1 Kristina Moll
A1 Anthony P. Monaco
A1 Angela T. Morgan
A1 Markus M. Nöthen
A1 Zdenka Pausova
A1 Craig E. Pennell
A1 Bruce F Pennington
A1 Kaitlyn M. Price
A1 Veera M. Rajagopal
A1 Frank Ramus
A1 Louis Richer
A1 Nuala H. Simpson
A1 Shelley Smith
A1 Margaret J. Snowling
A1 John Stein
A1 Lisa J. Strug
A1 Joel B. Talcott
A1 Henning Tiemeier
A1 Marc M.P. van de Schroeff
A1 Ellen Verhoef
A1 Kate E. Watkins
A1 Margaret Wilkinson
A1 Margaret J. Wright
A1 Cathy L. Barr
A1 Dorret I. Boomsma
A1 Manuel Carreiras
A1 Marie-Christine J. Franken
A1 Jeffrey R. Gruen
A1 Michelle Luciano
A1 Bertram Müller-Myhsok
A1 Dianne F. Newbury
A1 Richard K. Olson
A1 Silvia Paracchini
A1 Tomas Paus
A1 Robert Plomin
A1 Gerd Schulte-Körne
A1 Sheena Reilly
A1 J. Bruce Tomblin
A1 Elsje van Bergen
A1 Andrew J.O. Whitehouse
A1 Erik G. Willcutt
A1 Beate St Pourcain
A1 Clyde Francks
A1 Simon E. Fisher
YR 2021
UL http://biorxiv.org/content/early/2021/11/04/2021.11.04.466897.abstract
AB The use of spoken and written language is a capacity that is unique to humans. 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 relevant genetic architecture is complex, heterogeneous, and multifactorial, and yet to be investigated with well-powered studies. Here, 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, with total sample sizes ranging from 13,633 to 33,959 participants aged 5-26 years (12,411 to 27,180 for those with European ancestry, defined by principal component analyses). We identified a genome-wide significant association with word reading (rs11208009, p=1.098 × 10−8) independent of known loci associated with intelligence or educational attainment. All five reading-/language-related traits had robust SNP-heritability estimates (0.13–0.26), and genetic correlations between them were modest to high. Using genomic structural equation modelling, we found evidence for a shared genetic factor explaining the majority of variation in word and nonword reading, spelling, and phoneme awareness, which only partially overlapped with genetic variation contributing to nonword repetition, intelligence and educational attainment. A multivariate GWAS was performed to jointly analyse word and nonword reading, spelling, and phoneme awareness, maximizing power for follow-up investigation. Genetic correlation analysis of multivariate GWAS results with neuroimaging traits identified association with cortical surface area of the banks of the left superior temporal sulcus, a brain region with known links to processing of spoken and written language. Analysis of evolutionary annotations on the lineage that led to modern humans showed enriched heritability in regions depleted of Neanderthal variants. Together, these results provide new avenues for deciphering the biological underpinnings of these uniquely human traits.Competing Interest StatementThe authors have declared no competing interest.