Discovery of 42 genome-wide significant loci associated with dyslexia

23andMe Research Team; Quantitative Trait Working Group of the GenLang Consortium

doi:10.1038/s41588-022-01192-y

Discovery of 42 genome-wide significant loci associated with dyslexia

23andMe Research Team, Quantitative Trait Working Group of the GenLang Consortium

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48 Citations (Scopus)

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

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@article{c8eb4997f78945f196e7977481eed5bf,

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 = "{23andMe Research Team} and {Quantitative Trait Working Group of the GenLang Consortium} and Catherine Doust and Pierre Fontanillas and Else Eising and Gordon, {Scott D.} and Zhengjun Wang and G{\"o}kberk Alag{\"o}z and Barbara Molz and Stella Aslibekyan and Adam Auton and Elizabeth Babalola and Bell, {Robert K.} and Jessica Bielenberg and Katarzyna Bryc and Emily Bullis and Daniella Coker and Partida, {Gabriel Cuellar} and Devika Dhamija and Sayantan Das and Elson, {Sarah L.} and Teresa Filshtein and Kipper Fletez-Brant and Will Freyman and Gandhi, {Pooja M.} and Karl Heilbron and Barry Hicks and Hinds, {David A.} and Jewett, {Ethan M.} and Yunxuan Jiang and Katelyn Kukar and Lin, {Keng Han} and Maya Lowe and Jey McCreight and McIntyre, {Matthew H.} and Micheletti, {Steven J.} and Moreno, {Meghan E.} and Mountain, {Joanna L.} and Priyanka Nandakumar and Noblin, {Elizabeth S.} and Jared O{\textquoteright}Connell and Petrakovitz, {Aaron A.} and Poznik, {G. David} and Morgan Schumacher and Shastri, {Anjali J.} and Shelton, {Janie F.} and Jingchunzi Shi and Suyash Shringarpure and Allegrini, {Andrea G.} and Juha Kere and Plomin, {Robert J.} and Kaili Rimfeld",

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",

volume = "54",

pages = "1621--1629",

journal = "Nature Genetics",

issn = "1061-4036",

number = "11",

}

TY - JOUR

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

AU - 23andMe Research Team

AU - Quantitative Trait Working Group of the GenLang Consortium

AU - Doust, Catherine

AU - Fontanillas, Pierre

AU - Eising, Else

AU - Gordon, Scott D.

AU - Wang, Zhengjun

AU - Alagöz, Gökberk

AU - Molz, Barbara

AU - Aslibekyan, Stella

AU - Auton, Adam

AU - Babalola, Elizabeth

AU - Bell, Robert K.

AU - Bielenberg, Jessica

AU - Bryc, Katarzyna

AU - Bullis, Emily

AU - Coker, Daniella

AU - Partida, Gabriel Cuellar

AU - Dhamija, Devika

AU - Das, Sayantan

AU - Elson, Sarah L.

AU - Filshtein, Teresa

AU - Fletez-Brant, Kipper

AU - Freyman, Will

AU - Gandhi, Pooja M.

AU - Heilbron, Karl

AU - Hicks, Barry

AU - Hinds, David A.

AU - Jewett, Ethan M.

AU - Jiang, Yunxuan

AU - Kukar, Katelyn

AU - Lin, Keng Han

AU - Lowe, Maya

AU - McCreight, Jey

AU - McIntyre, Matthew H.

AU - Micheletti, Steven J.

AU - Moreno, Meghan E.

AU - Mountain, Joanna L.

AU - Nandakumar, Priyanka

AU - Noblin, Elizabeth S.

AU - O’Connell, Jared

AU - Petrakovitz, Aaron A.

AU - Poznik, G. David

AU - Schumacher, Morgan

AU - Shastri, Anjali J.

AU - Shelton, Janie F.

AU - Shi, Jingchunzi

AU - Shringarpure, Suyash

AU - Allegrini, Andrea G.

AU - Kere, Juha

AU - Plomin, Robert J.

AU - Rimfeld, Kaili

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.

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 - http://www.scopus.com/inward/record.url?scp=85142937214&partnerID=8YFLogxK

U2 - 10.1038/s41588-022-01192-y

DO - 10.1038/s41588-022-01192-y

M3 - Article

AN - SCOPUS:85142937214

SN - 1061-4036

VL - 54

SP - 1621

EP - 1629

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Discovery of 42 genome-wide significant loci associated with dyslexia

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