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Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities
- Source :
- Translational Psychiatry, 12, 1-9, Translational Psychiatry, 12(1):495. Nature Publishing Group, 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, Translational Psychiatry, 12 (1), Quantitative Trait Working Group of the GenLang Consortium 2022, ' Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities ', Translational psychiatry, vol. 12, no. 1, 495 . https://doi.org/10.1038/s41398-022-02250-z, Price, K M, Wigg, K G, Eising, E, Boomsma, D I, de Zeeuw, E L, Hottenga, J J, Jansen, P R, van Bergen, E, Lovett, M W, Strug, L J, Barr, C L & Quantitative Trait Working Group of the GenLang Consortium 2022, ' Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities ', Translational Psychiatry, vol. 12, 495, pp. 1-9 . https://doi.org/10.1038/s41398-022-02250-z, Translational Psychiatry, 12:495, 1-9. Nature Publishing Group, Translational Psychiatry, Transl. Psychiatry 12:495 (2022), Translational Psychiatry, 12, 1, pp. 1-9, Translational psychiatry, 12(1):495
- Publication Year :
- 2022
-
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.<br />Translational Psychiatry, 12 (1)<br />ISSN:2158-3188
- Subjects :
- Neuroinformatics
single nucleotide
Candidate gene
Autism Spectrum Disorder
Developmental dyslexia
autism spectrum disorder
QH426 Genetics
Polymorphism, Single Nucleotide
Neuronal migration
3124 Neurology and psychiatry
polymorphism
Dyslexia
Cellular and Molecular Neuroscience
All institutes and research themes of the Radboud University Medical Center
problem solving
SDG 3 - Good Health and Well-being
dyslexia
Humans
Kiaa0319
Family
humans
Children
QH426
Problem Solving
Biological Psychiatry
MCC
Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7]
genome-wide association study
Dyx1c1
Plasma-membrane
3rd-DAS
Psychiatry and Mental health
Susceptibility
RC0321
SDG 4 - Quality Education
RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Genome-Wide Association Study
Knockout mice
Subjects
Details
- Language :
- English
- ISSN :
- 21583188
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry, 12, 1-9, Translational Psychiatry, 12(1):495. Nature Publishing Group, 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, Translational Psychiatry, 12 (1), Quantitative Trait Working Group of the GenLang Consortium 2022, ' Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities ', Translational psychiatry, vol. 12, no. 1, 495 . https://doi.org/10.1038/s41398-022-02250-z, Price, K M, Wigg, K G, Eising, E, Boomsma, D I, de Zeeuw, E L, Hottenga, J J, Jansen, P R, van Bergen, E, Lovett, M W, Strug, L J, Barr, C L & Quantitative Trait Working Group of the GenLang Consortium 2022, ' Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities ', Translational Psychiatry, vol. 12, 495, pp. 1-9 . https://doi.org/10.1038/s41398-022-02250-z, Translational Psychiatry, 12:495, 1-9. Nature Publishing Group, Translational Psychiatry, Transl. Psychiatry 12:495 (2022), Translational Psychiatry, 12, 1, pp. 1-9, Translational psychiatry, 12(1):495
- Accession number :
- edsair.doi.dedup.....b8f62675903a80cd867fe01fb5f19891