Discovery of 42 genome-wide significant loci associated with dyslexia

Catherine Doust; Pierre Fontanillas; 23andMe Inc.; Else Eising; Scott D Gordon; Zhengjun Wang; Gökberk Alagöz; Barbara Molz; Beate St Pourcain; Clyde Francks; Riccardo E Marioni; Jingjing Zhao; Silvia Paracchini; Joel B Talcott; Anthony P Monaco; John F Stein; Jeffrey R Gruen; Richard K Olson; Erik G Willcutt; John C DeFries; Bruce F Pennington; Shelley D Smith; Margaret J Wright; Nicholas G Martin; Adam Auton; Timothy C Bates; Simon E Fisher; Michelle Luciano; M.P. van der Schroeff

doi:10.1038/s41588-022-01192-y

Discovery of 42 genome-wide significant loci associated with dyslexia

Catherine Doust, Pierre Fontanillas, 23andMe Inc., Else Eising, Scott D Gordon, Zhengjun Wang, Gökberk Alagöz, Barbara Molz, Beate St Pourcain, Clyde Francks, Riccardo E Marioni, Jingjing Zhao, Silvia Paracchini, Joel B Talcott, Anthony P Monaco, John F Stein, Jeffrey R Gruen, Richard K Olson, Erik G Willcutt, John C DeFriesBruce F Pennington, Shelley D Smith, Margaret J Wright, Nicholas G Martin, Adam Auton, Timothy C Bates, Simon E Fisher, Michelle Luciano, M.P. van der Schroeff

Otorhinolaryngology and Head and Neck Surgery

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Abstract

Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

Original language	English
Pages (from-to)	1621-1629
Number of pages	9
Journal	Nature Genetics
Volume	54
Issue number	11
DOIs	https://doi.org/10.1038/s41588-022-01192-y
Publication status	Published - Nov 2022

Bibliographical note

Funding Information:
We thank the research participants and employees of 23andMe Inc, the GenLang Consortium, the Brisbane Adults Reading Study, and the CRS. E.E., G.A., B.M., B.S.P., C.F. and S.E.F. are supported by the Max Planck Society (Germany). The CRS was supported by grants from the National Natural Science Foundation of China (Grant No. 61807023), Funds for Humanities and Social Sciences Research of the Ministry of Education (Grant No. 19YJC190023 and 17XJC190010) and General Project of Shaanxi Natural Science Basic Research Program (2018JQ8015) (Grant No. 2018JQ8015 and 2021JQ-309). S.P. is funded by the Royal Society. Acknowledgements for the GenLang Consortium appear in the Supplementary Note.

Publisher Copyright:
© 2022, The Author(s).

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Doust, C., Fontanillas, P., 23andMe Inc., Eising, E., Gordon, S. D., Wang, Z., Alagöz, G., Molz, B., Pourcain, B. S., Francks, C., Marioni, R. E., Zhao, J., Paracchini, S., Talcott, J. B., Monaco, A. P., Stein, J. F., Gruen, J. R., Olson, R. K., Willcutt, E. G., ... van der Schroeff, M. P. (2022). Discovery of 42 genome-wide significant loci associated with dyslexia. Nature Genetics, 54(11), 1621-1629. https://doi.org/10.1038/s41588-022-01192-y

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title = "Discovery of 42 genome-wide significant loci associated with dyslexia",

abstract = "Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.",

author = "Catherine Doust and Pierre Fontanillas and {23andMe Inc.} and Else Eising and Gordon, {Scott D} and Zhengjun Wang and G{\"o}kberk Alag{\"o}z and Barbara Molz and Pourcain, {Beate St} and Clyde Francks and Marioni, {Riccardo E} and Jingjing Zhao and Silvia Paracchini and Talcott, {Joel B} and Monaco, {Anthony P} and Stein, {John F} and Gruen, {Jeffrey R} and Olson, {Richard K} and Willcutt, {Erik G} and DeFries, {John C} and Pennington, {Bruce F} and Smith, {Shelley D} and Wright, {Margaret J} and Martin, {Nicholas G} and Adam Auton and Bates, {Timothy C} and Fisher, {Simon E} and Michelle Luciano and {van der Schroeff}, M.P.",

note = "Funding Information: We thank the research participants and employees of 23andMe Inc, the GenLang Consortium, the Brisbane Adults Reading Study, and the CRS. E.E., G.A., B.M., B.S.P., C.F. and S.E.F. are supported by the Max Planck Society (Germany). The CRS was supported by grants from the National Natural Science Foundation of China (Grant No. 61807023), Funds for Humanities and Social Sciences Research of the Ministry of Education (Grant No. 19YJC190023 and 17XJC190010) and General Project of Shaanxi Natural Science Basic Research Program (2018JQ8015) (Grant No. 2018JQ8015 and 2021JQ-309). S.P. is funded by the Royal Society. Acknowledgements for the GenLang Consortium appear in the Supplementary Note. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = nov,

doi = "10.1038/s41588-022-01192-y",

language = "English",

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Doust, C, Fontanillas, P, 23andMe Inc., Eising, E, Gordon, SD, Wang, Z, Alagöz, G, Molz, B, Pourcain, BS, Francks, C, Marioni, RE, Zhao, J, Paracchini, S, Talcott, JB, Monaco, AP, Stein, JF, Gruen, JR, Olson, RK, Willcutt, EG, DeFries, JC, Pennington, BF, Smith, SD, Wright, MJ, Martin, NG, Auton, A, Bates, TC, Fisher, SE, Luciano, M & van der Schroeff, MP 2022, 'Discovery of 42 genome-wide significant loci associated with dyslexia', Nature Genetics, vol. 54, no. 11, pp. 1621-1629. https://doi.org/10.1038/s41588-022-01192-y

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AU - Doust, Catherine

AU - Fontanillas, Pierre

AU - 23andMe Inc.

AU - Eising, Else

AU - Gordon, Scott D

AU - Wang, Zhengjun

AU - Alagöz, Gökberk

AU - Molz, Barbara

AU - Pourcain, Beate St

AU - Francks, Clyde

AU - Marioni, Riccardo E

AU - Zhao, Jingjing

AU - Paracchini, Silvia

AU - Talcott, Joel B

AU - Monaco, Anthony P

AU - Stein, John F

AU - Gruen, Jeffrey R

AU - Olson, Richard K

AU - Willcutt, Erik G

AU - DeFries, John C

AU - Pennington, Bruce F

AU - Smith, Shelley D

AU - Wright, Margaret J

AU - Martin, Nicholas G

AU - Auton, Adam

AU - Bates, Timothy C

AU - Fisher, Simon E

AU - Luciano, Michelle

AU - van der Schroeff, M.P.

N1 - Funding Information: We thank the research participants and employees of 23andMe Inc, the GenLang Consortium, the Brisbane Adults Reading Study, and the CRS. E.E., G.A., B.M., B.S.P., C.F. and S.E.F. are supported by the Max Planck Society (Germany). The CRS was supported by grants from the National Natural Science Foundation of China (Grant No. 61807023), Funds for Humanities and Social Sciences Research of the Ministry of Education (Grant No. 19YJC190023 and 17XJC190010) and General Project of Shaanxi Natural Science Basic Research Program (2018JQ8015) (Grant No. 2018JQ8015 and 2021JQ-309). S.P. is funded by the Royal Society. Acknowledgements for the GenLang Consortium appear in the Supplementary Note. Publisher Copyright: © 2022, The Author(s).

PY - 2022/11

Y1 - 2022/11

N2 - Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.

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Discovery of 42 genome-wide significant loci associated with dyslexia

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