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

TY - JOUR

T1 - Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people

AU - GenLang Consortium

AU - Eising, Else

AU - Mirza-Schreiber, Nazanin

AU - de Zeeuw, Eveline L

AU - Wang, Carol A

AU - Truong, Dongnhu T

AU - Allegrini, Andrea G

AU - Shapland, Chin Yang

AU - Zhu, Gu

AU - Wigg, Karen G

AU - Gerritse, Margot L

AU - Molz, Barbara

AU - Alagöz, Gökberk

AU - Gialluisi, Alessandro

AU - Abbondanza, Filippo

AU - Rimfeld, Kaili

AU - van Donkelaar, Marjolein

AU - Liao, Zhijie

AU - Jansen, Philip R

AU - Andlauer, Till F M

AU - Bates, Timothy C

AU - Bernard, Manon

AU - Blokland, Kirsten

AU - Bonte, Milene

AU - Børglum, Anders D

AU - Bourgeron, Thomas

AU - Brandeis, Daniel

AU - Ceroni, Fabiola

AU - Csépe, Valéria

AU - Dale, Philip S

AU - de Jong, Peter F

AU - DeFries, John C

AU - Démonet, Jean-François

AU - Demontis, Ditte

AU - Feng, Yu

AU - Gordon, Scott D

AU - Guger, Sharon L

AU - Hayiou-Thomas, Marianna E

AU - Hernández-Cabrera, Juan A

AU - Hottenga, Jouke-Jan

AU - Hulme, Charles

AU - Kere, Juha

AU - Kerr, Elizabeth N

AU - Koomar, Tanner

AU - Landerl, Karin

AU - Leonard, Gabriel T

AU - Lovett, Maureen W

AU - Lyytinen, Heikki

AU - Martin, Nicholas G

AU - Moll, Kristina

AU - Snowling, Margaret J

N1 - © 2022 the Author(s)

PY - 2022/8/30

Y1 - 2022/8/30

N2 - 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.

AB - 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.

KW - Genome-Wide Association Study

KW - Humans

KW - Individuality

KW - Language

KW - Polymorphism, Single Nucleotide

KW - Reading

U2 - 10.1073/pnas.2202764119

DO - 10.1073/pnas.2202764119

M3 - Article

C2 - 35998220

SN - 0027-8424

VL - 119

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

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

IS - 35

M1 - e2202764119

ER -