| Literature DB >> 35998220 |
Else Eising1, Nazanin Mirza-Schreiber2, Eveline L de Zeeuw3, Carol A Wang4,5, Dongnhu T Truong6, Andrea G Allegrini7, Chin Yang Shapland8,9, Gu Zhu10, Karen G Wigg11, Margot L Gerritse1, Barbara Molz1, Gökberk Alagöz1, Alessandro Gialluisi12,13,14, Filippo Abbondanza15, Kaili Rimfeld7,16, Marjolein van Donkelaar1, Zhijie Liao17, Philip R Jansen18,19,20, Till F M Andlauer12,21, Timothy C Bates22, Manon Bernard23, Kirsten Blokland24, Milene Bonte25, Anders D Børglum26,27,28, Thomas Bourgeron29, Daniel Brandeis30,31,32,33, Fabiola Ceroni34,35, Valéria Csépe36,37, Philip S Dale38, Peter F de Jong39, John C DeFries40,41, Jean-François Démonet42, Ditte Demontis26,27, Yu Feng11, Scott D Gordon10, Sharon L Guger43, Marianna E Hayiou-Thomas44, Juan A Hernández-Cabrera45, Jouke-Jan Hottenga3, Charles Hulme46, Juha Kere47,48, Elizabeth N Kerr43,49,50, Tanner Koomar51, Karin Landerl52,53, Gabriel T Leonard54, Maureen W Lovett24,50, Heikki Lyytinen55, Nicholas G Martin10, Angela Martinelli15, Urs Maurer56, Jacob J Michaelson51, Kristina Moll57, Anthony P Monaco58, Angela T Morgan59,60,61, Markus M Nöthen62, Zdenka Pausova23,63, Craig E Pennell4,5,64, Bruce F Pennington65, Kaitlyn M Price11,24,66, Veera M Rajagopal26,27, Franck Ramus67, Louis Richer68, Nuala H Simpson69, Shelley D Smith70, Margaret J Snowling69,71, John Stein72, Lisa J Strug73,74, Joel B Talcott75, Henning Tiemeier18,76, Marc P van der Schroeff77,78, Ellen Verhoef1, Kate E Watkins69, Margaret Wilkinson24, Margaret J Wright79, Cathy L Barr11,24,66, Dorret I Boomsma3,80,81, Manuel Carreiras82,83,84, Marie-Christine J Franken77, Jeffrey R Gruen6, Michelle Luciano22, Bertram Müller-Myhsok12,85, Dianne F Newbury35, Richard K Olson40, Silvia Paracchini15, Tomáš Paus86, Robert Plomin7, Sheena Reilly59,87, Gerd Schulte-Körne57, J Bruce Tomblin88, Elsje van Bergen3,80,89, Andrew J O Whitehouse90, Erik G Willcutt41, Beate St Pourcain1,8,91, Clyde Francks1,91,92, Simon E Fisher1,91.
Abstract
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.Entities:
Keywords: genome-wide association study; language; meta-analysis; reading
Mesh：
Year: 2022 PMID： 35998220 PMCID： PMC9436320 DOI： 10.1073/pnas.2202764119
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 12.779