@article {448, title = {Discovery of 42 genome-wide significant loci associated with dyslexia}, journal = {Nature Genetics}, volume = {54}, year = {2022}, pages = {1621{\textendash}1629}, 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.

}, doi = {10.1038/s41588-022-01192-y}, author = {Doust, Catherine and Fontanillas, Pierre and Eising, Else and Gordon, Scott D and Wang, Zhengjun and Alag{\"o}z, G{\"o}kberk and Molz, Barbara and 23andMe Research Team and Quantitative Trait Working Group of the GenLang Consortium and Pourcain, Beate St and Francks, Clyde and Marioni, Riccardo E and Zhao, Jingjing and Paracchini, Silvia 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 Auton, Adam and Bates, Timothy C and Fisher, Simon E and Luciano, Michelle} } @article {462, title = {Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities}, journal = {Translational Psychiatry}, volume = {12}, year = {2022}, pages = {495}, 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\ \×\ 10\–2, threshold = 2.5\ \×\ 10\–2). For the GenLang Cohort (n\ =\ 26,558), SNPs in DOCK7 and CDH4 showed significant association for the NM/AG hypothesis (sFDR q\ =\ 1.02\ \×\ 10\–2). To make the GenLang dataset more similar to Toronto, we repeated the analysis restricting to samples selected for reading/language deficits (n\ =\ 4152). In this GenLang selected subset, we found significant association for a locus intergenic between BTG3-C21orf91 for both hypotheses (sFDR q\ \<\ 9.00\ \×\ 10\–4). This study contributes candidate loci to the genetics of word reading. Data also suggest that, although different variants may be involved, alleles implicated in ASD risk may be found in the same genes as those implicated in word reading. This finding is limited to the Toronto sample suggesting that ascertainment influences genetic associations.

}, doi = {10.1038/s41398-022-02250-z}, author = {Price, Kaitlyn M and Wigg, Karen G and Eising, Else and Feng, Yu and Blokland, Kirsten and Wilkinson, Margaret and Kerr, Elizabeth N and Guger, Sharon L and Quantitative Trait Working Group of the GenLang Consortium and Fisher, Simon E and Lovett, Maureen W and Strug, Lisa J and Barr, Cathy L} }