Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities

TitleHypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities
Publication TypeJournal Article
Year of Publication2022
AuthorsPrice, KM, Wigg, KG, Eising, E, Feng, Y, Blokland, K, Wilkinson, M, Kerr, EN, Guger, SL, Consortium, QTrait Work, Fisher, SE, Lovett, MW, Strug, LJ, Barr, CL
JournalTranslational Psychiatry
Volume12
Pagination495
Abstract

Reading Disability (RD) is often characterized by difficulties in the phonology of the language. While the molecular mechanisms underlying it are largely undetermined, loci are being revealed by genome-wide association studies (GWAS). In a previous GWAS for word reading (Price, 2020), we observed that top single-nucleotide polymorphisms (SNPs) were located near to or in genes involved in neuronal migration/axon guidance (NM/AG) or loci implicated in autism spectrum disorder (ASD). A prominent theory of RD etiology posits that it involves disturbed neuronal migration, while potential links between RD-ASD have not been extensively investigated. To improve power to identify associated loci, we up-weighted variants involved in NM/AG or ASD, separately, and performed a new Hypothesis-Driven (HD)-GWAS. The approach was applied to a Toronto RD sample and a meta-analysis of the GenLang Consortium. For the Toronto sample (n = 624), no SNPs reached significance; however, by gene-set analysis, the joint contribution of ASD-related genes passed the threshold (p 1.45 $\times$ 10-

DOI10.1038/s41398-022-02250-z