Discovery of 42 genome-wide significant loci associated with dyslexia

Doust, Catherine; Fontanillas, Pierre; Eising, Else; Gordon, Scott D; Wang, Zhengjun; Alagöz, Gökberk; Moltz, Barbara; 23andMe Research Team; Quantitative Trait Working Group of the GenLang Consortium; St Pourcain, Beate; Francks, Clyde; Marioni, Riccardo E; Zhao, Jingjing; Paracchini, Silvia; Talcott, Joel B; Monaco, Anthony P; Stein, John F; Gruen, Jeffrey R; Olson, Richard K; Willcutt, Erik G; DeFries, John C; Pennington, Bruce F; Smith, Shelley D; Wright, Margaret J; Martin, Nicholas G; Auton, Adam; Bates, Timothy C; Fisher, Simon E; Luciano, Michelle

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.

Citation

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 , Willcutt , E G , DeFries , J C , Pennington , B F , Smith , S D , Wright , M J , Martin , N G , Auton , A , Bates , T C , Fisher , S E & 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

Publication

Nature Genetics

Status

Peer reviewed

DOI

https://doi.org/10.1038/s41588-022-01192-y

ISSN

1061-4036

Type

Journal article

Rights

Copyright © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Description

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.

Collections

University of St Andrews Research

URI

http://hdl.handle.net/10023/26236

St Andrews Research Repository