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

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

doi:10.1073/pnas.2202764119

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

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. BatesManon 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

UWA Centre for Child Health Research (affiliated with the Telethon Kids Institute)

Research output: Contribution to journal › Article › peer-review

8 Citations (Web of Science)

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.

Original language	English
Article number	e2202764119
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	35
DOIs	https://doi.org/10.1073/pnas.2202764119
Publication status	Published - 30 Aug 2022

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10.1073/pnas.2202764119Licence: CC BY

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Eising, E., Mirza-Schreiber, N., de Zeeuw, E. L., Wang, C. A., Truong, D. T., Allegrini, A. G., Shapland, C. Y., Zhu, G., Wigg, K. G., Gerritse, M. L., Molz, B., Alagöz, G., Gialluisi, A., Abbondanza, F., Rimfeld, K., van Donkelaar, M., Liao, Z., Jansen, P. R., Andlauer, T. F. M., ... Fisher, S. E. (2022). 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, 119(35), [e2202764119]. https://doi.org/10.1073/pnas.2202764119

@article{7457ded7c0bf4ad3a88136c1a4fdab35,

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

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.",

keywords = "genome-wide association study, language, meta-analysis, reading",

author = "Else Eising and Nazanin Mirza-Schreiber and {de Zeeuw}, {Eveline L.} and Wang, {Carol A.} and Truong, {Dongnhu T.} and Allegrini, {Andrea G.} and Shapland, {Chin Yang} and Gu Zhu and Wigg, {Karen G.} and Gerritse, {Margot L.} and Barbara Molz and G{\"o}kberk Alag{\"o}z and Alessandro Gialluisi and Filippo Abbondanza and Kaili Rimfeld and {van Donkelaar}, Marjolein and Zhijie Liao and Jansen, {Philip R.} and Andlauer, {Till F.M.} and Bates, {Timothy C.} and Manon Bernard and Kirsten Blokland and Milene Bonte and B{\o}rglum, {Anders D.} and Thomas Bourgeron and Daniel Brandeis and Fabiola Ceroni and Val{\'e}ria Cs{\'e}pe and Dale, {Philip S.} and {de Jong}, {Peter F.} and DeFries, {John C.} and D{\'e}monet, {Jean Fran{\c c}ois} and Ditte Demontis and Yu Feng and Gordon, {Scott D.} and Guger, {Sharon L.} and Hayiou-Thomas, {Marianna E.} and Hern{\'a}ndez-Cabrera, {Juan A.} and Hottenga, {Jouke Jan} and Charles Hulme and Juha Kere and Kerr, {Elizabeth N.} and Tanner Koomar and Karin Landerl and Leonard, {Gabriel T.} and Lovett, {Maureen W.} and Heikki Lyytinen and Martin, {Nicholas G.} and Angela Martinelli and Urs Maurer and Michaelson, {Jacob J.} and Kristina Moll and Monaco, {Anthony P.} and Morgan, {Angela T.} and N{\"o}then, {Markus M.} and Zdenka Pausova and Pennell, {Craig E.} and Pennington, {Bruce F.} and Price, {Kaitlyn M.} and Rajagopal, {Veera M.} and Franck Ramus and Louis Richer and Simpson, {Nuala H.} and Smith, {Shelley D.} and Snowling, {Margaret J.} and John Stein and Strug, {Lisa J.} and Talcott, {Joel B.} and Henning Tiemeier and {van der Schroeff}, {Marc P.} and Ellen Verhoef and Watkins, {Kate E.} and Margaret Wilkinson and Wright, {Margaret J.} and Barr, {Cathy L.} and Boomsma, {Dorret I.} and Manuel Carreiras and Franken, {Marie Christine J.} and Gruen, {Jeffrey R.} and Michelle Luciano and Bertram M{\"u}ller-Myhsok and Newbury, {Dianne F.} and Olson, {Richard K.} and Silvia Paracchini and Tom{\'a}{\v s} Paus and Robert Plomin and Sheena Reilly and Gerd Schulte-K{\"o}rne and Tomblin, {J. Bruce} and {van Bergen}, Elsje and Whitehouse, {Andrew J.O.} and Willcutt, {Erik G.} and {St Pourcain}, Beate and Clyde Francks and Fisher, {Simon E.}",

year = "2022",

month = aug,

day = "30",

doi = "10.1073/pnas.2202764119",

language = "English",

volume = "119",

journal = "National Academy of Sciences, Proceedings",

issn = "0027-8424",

publisher = "NATL ACAD SCIENCES",

number = "35",

}

Eising, E, Mirza-Schreiber, N, de Zeeuw, EL, Wang, CA, Truong, DT, Allegrini, AG, Shapland, CY, Zhu, G, Wigg, KG, Gerritse, ML, Molz, B, Alagöz, G, Gialluisi, A, Abbondanza, F, Rimfeld, K, van Donkelaar, M, Liao, Z, Jansen, PR, Andlauer, TFM, Bates, TC, Bernard, M, Blokland, K, Bonte, M, Børglum, AD, Bourgeron, T, Brandeis, D, Ceroni, F, Csépe, V, Dale, PS, de Jong, PF, DeFries, JC, Démonet, JF, Demontis, D, Feng, Y, Gordon, SD, Guger, SL, Hayiou-Thomas, ME, Hernández-Cabrera, JA, Hottenga, JJ, Hulme, C, Kere, J, Kerr, EN, Koomar, T, Landerl, K, Leonard, GT, Lovett, MW, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, JJ, Moll, K, Monaco, AP, Morgan, AT, Nöthen, MM, Pausova, Z, Pennell, CE, Pennington, BF, Price, KM, Rajagopal, VM, Ramus, F, Richer, L, Simpson, NH, Smith, SD, Snowling, MJ, Stein, J, Strug, LJ, Talcott, JB, Tiemeier, H, van der Schroeff, MP, Verhoef, E, Watkins, KE, Wilkinson, M, Wright, MJ, Barr, CL, Boomsma, DI, Carreiras, M, Franken, MCJ, Gruen, JR, Luciano, M, Müller-Myhsok, B, Newbury, DF, Olson, RK, Paracchini, S, Paus, T, Plomin, R, Reilly, S, Schulte-Körne, G, Tomblin, JB, van Bergen, E, Whitehouse, AJO, Willcutt, EG, St Pourcain, B, Francks, C & Fisher, SE 2022, '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, vol. 119, no. 35, e2202764119. https://doi.org/10.1073/pnas.2202764119

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people. / Eising, Else; Mirza-Schreiber, Nazanin; de Zeeuw, Eveline L. et al.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 35, e2202764119, 30.08.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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

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 - Martinelli, Angela

AU - Maurer, Urs

AU - Michaelson, Jacob J.

AU - Moll, Kristina

AU - Monaco, Anthony P.

AU - Morgan, Angela T.

AU - Nöthen, Markus M.

AU - Pausova, Zdenka

AU - Pennell, Craig E.

AU - Pennington, Bruce F.

AU - Price, Kaitlyn M.

AU - Rajagopal, Veera M.

AU - Ramus, Franck

AU - Richer, Louis

AU - Simpson, Nuala H.

AU - Smith, Shelley D.

AU - Snowling, Margaret J.

AU - Stein, John

AU - Strug, Lisa J.

AU - Talcott, Joel B.

AU - Tiemeier, Henning

AU - van der Schroeff, Marc P.

AU - Verhoef, Ellen

AU - Watkins, Kate E.

AU - Wilkinson, Margaret

AU - Wright, Margaret J.

AU - Barr, Cathy L.

AU - Boomsma, Dorret I.

AU - Carreiras, Manuel

AU - Franken, Marie Christine J.

AU - Gruen, Jeffrey R.

AU - Luciano, Michelle

AU - Müller-Myhsok, Bertram

AU - Newbury, Dianne F.

AU - Olson, Richard K.

AU - Paracchini, Silvia

AU - Paus, Tomáš

AU - Plomin, Robert

AU - Reilly, Sheena

AU - Schulte-Körne, Gerd

AU - Tomblin, J. Bruce

AU - van Bergen, Elsje

AU - Whitehouse, Andrew J.O.

AU - Willcutt, Erik G.

AU - St Pourcain, Beate

AU - Francks, Clyde

AU - Fisher, Simon E.

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 - language

KW - meta-analysis

KW - reading

UR - http://www.scopus.com/inward/record.url?scp=85136345356&partnerID=8YFLogxK

U2 - 10.1073/pnas.2202764119

DO - 10.1073/pnas.2202764119

M3 - Article

C2 - 35998220

AN - SCOPUS:85136345356

SN - 0027-8424

VL - 119

JO - National Academy of Sciences, Proceedings

JF - National Academy of Sciences, Proceedings

IS - 35

M1 - e2202764119

ER -

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

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

Abstract

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Other files and links

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Improving clinical outcomes for children with autism spectrum disorder: A research program spanning basic, clinical and implementation science

A Genome Wide Search for Genes Underlying the Developmental Origins of Health and Disease

403981: Childhood Precursors of Adult Cardiovascular Disease, Obesity and Diabetes- 16 Year Follow up of a Longitudinal Cohort

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