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

Else Eising; Nazinin Mirza-Schreiber; Eveline L. de Zeeuw; Carol A. Wang; Dongnhu T. Truong; Andrea G. Allegrini; Chin Yang Shapland; Gu Zhu; Karen G. Wigg; Margot 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 Leonard; Maureen W. Lovett; Heikki Lyytinen; Nicholas G. Martin; Angela Martinelli; Urs Maurer; Jacob Michaelson; Kristina Moll; Anthony P. Monaco; Angela T. Morgan; Markus M. Nőthen; Zdenka Pausova; Craig E. Pennell; Bruce F. Pennington; Kaitlyn M. Price; Veera M. Rajagopal; Franck Ramus; Louis Richer; Nuala H. Simpson; Shelley Smith; Margaret J. Snowling; John Stein; Lisa J. Strug; Joel B. Talcott; Henning Tiemeier; Marc M.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 .  Olson; Silvia Paracchini; Tomáš Paus; Robert Plomin; Sheena Reilly; Gerd Schulte-Körne; 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, Nazinin Mirza-Schreiber, Eveline L. de Zeeuw, Carol A. Wang, Dongnhu T. Truong, Andrea G. Allegrini, Chin Yang Shapland, Gu Zhu, Karen G. Wigg, Margot 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 Leonard, Maureen W. Lovett, Heikki Lyytinen, Nicholas G. Martin, Angela Martinelli, Urs Maurer, Jacob Michaelson, Kristina Moll, Anthony P. Monaco, Angela T. Morgan, Markus M. Nőthen, Zdenka Pausova, Craig E. Pennell, Bruce F. Pennington, Kaitlyn M. Price, Veera M. Rajagopal, Franck Ramus, Louis Richer, Nuala H. Simpson, Shelley Smith, Margaret J. Snowling, John Stein, Lisa J. Strug, Joel B. Talcott, Henning Tiemeier, Marc M.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 . Olson, Silvia Paracchini, Tomáš Paus, Robert Plomin, Sheena Reilly, Gerd Schulte-Körne, Bruce Tomblin, Elsje van Bergen, Andrew J.O. Whitehouse, Erik G. Willcutt, Beate St Pourcain, Clyde Francks, Simon E. Fisher^*

^*Corresponding author for this work

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40 Citations (Scopus)

11 Downloads (Pure)

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
Number of pages	12
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	119
Issue number	35
Early online date	23 Aug 2022
DOIs	https://doi.org/10.1073/pnas.2202764119
Publication status	Published - 30 Aug 2022

Keywords

Reading
Language
Genome-wide association study
Meta-analysis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1073/pnas.2202764119Licence: CC BY

Eising-2022-Genome-wide-analyses-of-individual-PNAS-119-5-e2202764119-CCBY
Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
Final published version, 1.75 MBLicence: CC BY

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Dr Silvia Paracchini - Public Enhancemen: Is there a link between asymmetries and congnition
Paracchini, S. (PI)
The Royal Society
27/05/18 → 26/05/22
Project: Standard

Genome-wide analyses of individual differences in quantitatively assessed reading- and language-related skills in up to 34,000 people (code)
Paracchini, S. (Creator), GitHub, 2022
https://gitlab.gwdg.de/else.eising/genlang_quantitative_trait_gwasma
Dataset: Software

Cite this

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., 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), Article e2202764119. https://doi.org/10.1073/pnas.2202764119

@article{9d568cd632464956a351c451e6febd63,

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 = "Reading, Language, Genome-wide association study, Meta-analysis",

author = "Else Eising and Nazinin 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 Margot Gerritse 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 Jean-Fran{\c c}ois D{\'e}monet 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 Jouke-Jan Hottenga and Charles Hulme and Juha Kere and Kerr, {Elizabeth N.} and Tanner Koomar and Karin Landerl and Gabriel Leonard and Lovett, {Maureen W.} and Heikki Lyytinen and Martin, {Nicholas G.} and Angela Martinelli and Urs Maurer and Jacob Michaelson and Kristina Moll and Monaco, {Anthony P.} and Morgan, {Angela T.} and N{\H 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 Shelley Smith and Snowling, {Margaret J.} and John Stein and Strug, {Lisa J.} and Talcott, {Joel B.} and Henning Tiemeier and {van der Schroeff}, {Marc M.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 .} and Silvia Paracchini and Tom{\'a}{\v s} Paus and Robert Plomin and Sheena Reilly and Gerd Schulte-K{\"o}rne and Bruce Tomblin and {van Bergen}, Elsje and Whitehouse, {Andrew J.O.} and Willcutt, {Erik G.} and {St Pourcain}, Beate and Clyde Francks and Fisher, {Simon E.}",

note = "Funding: SP and FA are supported by the Royal Society (UF150663; RGF\EA\180141).",

year = "2022",

month = aug,

day = "30",

doi = "10.1073/pnas.2202764119",

language = "English",

volume = "119",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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, M, 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, J-F, Demontis, D, Feng, Y, Gordon, SD, Guger, SL, Hayiou-Thomas, ME, Hernández-Cabrera, JA, Hottenga, J-J, Hulme, C, Kere, J, Kerr, EN, Koomar, T, Landerl, K, Leonard, G, Lovett, MW, Lyytinen, H, Martin, NG, Martinelli, A, Maurer, U, Michaelson, J, Moll, K, Monaco, AP, Morgan, AT, Nőthen, MM, Pausova, Z, Pennell, CE, Pennington, BF, Price, KM, Rajagopal, VM, Ramus, F, Richer, L, Simpson, NH, Smith, S, Snowling, MJ, Stein, J, Strug, LJ, Talcott, JB, Tiemeier, H, van der Schroeff, MMP, Verhoef, E, Watkins, KE, Wilkinson, M, Wright, MJ, Barr, CL, Boomsma, DI, Carreiras, M, Franken, M-CJ, Gruen, JR, Luciano, M, Müller-Myhsok, B, Newbury, DF, Olson, R, Paracchini, S, Paus, T, Plomin, R, Reilly, S, Schulte-Körne, G, Tomblin, B, 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, Nazinin; 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, Nazinin

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

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

AU - Lovett, Maureen W.

AU - Lyytinen, Heikki

AU - Martin, Nicholas G.

AU - Martinelli, Angela

AU - Maurer, Urs

AU - Michaelson, Jacob

AU - Moll, Kristina

AU - Monaco, Anthony P.

AU - Morgan, Angela T.

AU - Nőthen, 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

AU - Snowling, Margaret J.

AU - Stein, John

AU - Strug, Lisa J.

AU - Talcott, Joel B.

AU - Tiemeier, Henning

AU - van der Schroeff, Marc M.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 .

AU - Paracchini, Silvia

AU - Paus, Tomáš

AU - Plomin, Robert

AU - Reilly, Sheena

AU - Schulte-Körne, Gerd

AU - Tomblin, 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.

N1 - Funding: SP and FA are supported by the Royal Society (UF150663; RGF\EA\180141).

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 - Reading

KW - Language

KW - Genome-wide association study

KW - Meta-analysis

U2 - 10.1073/pnas.2202764119

DO - 10.1073/pnas.2202764119

M3 - Article

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 -

Eising E, Mirza-Schreiber N, de Zeeuw EL, Wang CA, Truong DT, Allegrini AG et al. 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. 2022 Aug 30;119(35):e2202764119. Epub 2022 Aug 23. 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

Abstract

Keywords

UN SDGs

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Dr Silvia Paracchini - Public Enhancemen: Is there a link between asymmetries and congnition

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

Cite this