Discovery of 42 genome-wide significant loci associated with dyslexia

Catherine Doust; Pierre Fontanillas; Else Eising; Scott D Gordon; Zhengjun Wang; Gökberk Alagöz; Barbara Moltz; 23andMe Research Team; Quantitative Trait Working Group of the GenLang Consortium; 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

doi:10.1038/s41588-022-01192-y

Discovery of 42 genome-wide significant loci associated with dyslexia

Catherine Doust, Pierre Fontanillas, Else Eising, Scott D Gordon, Zhengjun Wang, Gökberk Alagöz, Barbara Moltz, 23andMe Research Team, Quantitative Trait Working Group of the GenLang Consortium, 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 WillcuttJohn C DeFries, Bruce F Pennington, Shelley D Smith, Margaret J Wright, Nicholas G Martin, Adam Auton, Timothy C Bates, Simon E Fisher, Michelle Luciano^*

^*Corresponding author for this work

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

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
DOIs	https://doi.org/10.1038/s41588-022-01192-y
Publication status	Published - 20 Oct 2022

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Doust, C., Fontanillas, P., Eising, E., Gordon, S. D., Wang, Z., Alagöz, G., Moltz, B., 23andMe Research Team, Quantitative Trait Working Group of the GenLang Consortium, St Pourcain, B., Francks, C., Marioni, R. E., Zhao, J., Paracchini, S., Talcott, J. B., Monaco, A. P., Stein, J. F., Gruen, J. R., Olson, R. K., ... Luciano, M. (2022). Discovery of 42 genome-wide significant loci associated with dyslexia. Nature Genetics, 54, 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 Else Eising and Gordon, \{Scott D\} and Zhengjun Wang and G{\"o}kberk Alag{\"o}z and Barbara Moltz and \{23andMe Research Team\} and \{Quantitative Trait Working Group of the GenLang Consortium\} and \{St Pourcain\}, Beate 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",

note = "Funding: EE, GA, BM, BSP, CF and SEF are supported by the Max Planck Society (Germany). The Chinese Reading Study was supported by grants from the National Natural Science Foundation of China Youth Project (Grant No. 61807023), the Youth Fund for Humanities and Social Sciences Research of the Ministry of Education (Grant No. 19YJC190023 and 17XJC190010), and the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2021JQ-309). SP is funded by the Royal Society.",

year = "2022",

month = oct,

day = "20",

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

language = "English",

volume = "54",

pages = "1621--1629",

journal = "Nature Genetics",

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Doust, C, Fontanillas, P, Eising, E, Gordon, SD, Wang, Z, Alagöz, G, Moltz, B, 23andMe Research Team, Quantitative Trait Working Group of the GenLang Consortium, St Pourcain, B, 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 2022, 'Discovery of 42 genome-wide significant loci associated with dyslexia', Nature Genetics, vol. 54, pp. 1621-1629. https://doi.org/10.1038/s41588-022-01192-y

TY - JOUR

T1 - Discovery of 42 genome-wide significant loci associated with dyslexia

AU - Doust, Catherine

AU - Fontanillas, Pierre

AU - Eising, Else

AU - Gordon, Scott D

AU - Wang, Zhengjun

AU - Alagöz, Gökberk

AU - Moltz, Barbara

AU - 23andMe Research Team

AU - Quantitative Trait Working Group of the GenLang Consortium

AU - St Pourcain, Beate

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

N1 - Funding: EE, GA, BM, BSP, CF and SEF are supported by the Max Planck Society (Germany). The Chinese Reading Study was supported by grants from the National Natural Science Foundation of China Youth Project (Grant No. 61807023), the Youth Fund for Humanities and Social Sciences Research of the Ministry of Education (Grant No. 19YJC190023 and 17XJC190010), and the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2021JQ-309). SP is funded by the Royal Society.

PY - 2022/10/20

Y1 - 2022/10/20

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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85142937214

U2 - 10.1038/s41588-022-01192-y

DO - 10.1038/s41588-022-01192-y

M3 - Article

SN - 1061-4036

VL - 54

SP - 1621

EP - 1629

JO - Nature Genetics

JF - Nature Genetics

ER -

Discovery of 42 genome-wide significant loci associated with dyslexia

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Biology of dyslexia: A genetic study to dissect the biology of dyslexia

Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia (Nature Genetics, (2022), 54, 11, (1621-1629), 10.1038/s41588-022-01192-y)