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Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities
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dc.contributor.author | Price, Kaitlyn M. | |
dc.contributor.author | Wigg, Karen G. | |
dc.contributor.author | Eising, Else | |
dc.contributor.author | Feng, Yu | |
dc.contributor.author | Blokland, Kirsten | |
dc.contributor.author | Wilkinson, Margaret | |
dc.contributor.author | Kerr, Elizabeth N. | |
dc.contributor.author | Guger, Sharon L. | |
dc.contributor.author | Quantitative Trait Working Group of the GenLang Consortium | |
dc.contributor.author | Fisher, Simon E. | |
dc.contributor.author | Lovett, Maureen W. | |
dc.contributor.author | Strug, Lisa J. | |
dc.contributor.author | Barr, Cathy L. | |
dc.contributor.author | Paracchini, Silvia | |
dc.date.accessioned | 2022-12-21T13:30:02Z | |
dc.date.available | 2022-12-21T13:30:02Z | |
dc.date.issued | 2022-11-29 | |
dc.identifier | 281882993 | |
dc.identifier | b7fdeac7-d40e-4695-acab-10894774ede6 | |
dc.identifier | 85142921133 | |
dc.identifier | 000890265900003 | |
dc.identifier.citation | Price , K M , Wigg , K G , Eising , E , Feng , Y , Blokland , K , Wilkinson , M , Kerr , E N , Guger , S L , Quantitative Trait Working Group of the GenLang Consortium , Fisher , S E , Lovett , M W , Strug , L J , Barr , C L & Paracchini , S 2022 , ' Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities ' , Translational Psychiatry , vol. 12 , 495 . https://doi.org/10.1038/s41398-022-02250-z | en |
dc.identifier.issn | 2158-3188 | |
dc.identifier.other | ORCID: /0000-0001-9934-8602/work/121754306 | |
dc.identifier.other | PubMedCentral: PMC9709072 | |
dc.identifier.uri | https://hdl.handle.net/10023/26639 | |
dc.description | Funding: Support for the Toronto project was provided by grants from the Canadian Institutes of Health Research (MOP-133440 and PJT-180419). K.P. was supported by the Hospital for Sick Children Research Training Program. E.E. and S.E.F. are supported by the Max Planck Society. The St. Andrews Bioinformatics Unit is funded by Wellcome Trust Grants 105621/Z/14/Z and 204821/Z/16/Z. | en |
dc.description.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. | |
dc.format.extent | 9 | |
dc.format.extent | 702891 | |
dc.language.iso | eng | |
dc.relation.ispartof | Translational Psychiatry | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | QH426 Genetics | en |
dc.subject | 3rd-DAS | en |
dc.subject | MCC | en |
dc.subject.lcc | RC0321 | en |
dc.subject.lcc | QH426 | en |
dc.title | Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities | en |
dc.type | Journal article | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Centre for Biophotonics | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.contributor.institution | University of St Andrews. St Andrews Bioinformatics Unit | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.identifier.doi | https://doi.org/10.1038/s41398-022-02250-z | |
dc.description.status | Peer reviewed | en |
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