Journal article
Hypothesis-driven genome-wide association studies provide novel insights into genetics of reading disabilities
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 686.4KB, Terms of use)
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- Publisher copy:
- 10.1038/s41398-022-02250-z
- Publisher:
- Springer Nature
- Journal:
- Translational Psychiatry More from this journal
- Volume:
- 12
- Article number:
- 495
- Publication date:
- 2022-11-29
- Acceptance date:
- 2022-11-03
- DOI:
- EISSN:
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2158-3188
- Keywords:
- Pubs id:
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1300818
- Local pid:
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pubs:1300818
- Deposit date:
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2022-11-09
Terms of use
- Copyright holder:
- Price et al.
- Copyright date:
- 2022
- Rights statement:
- 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.
- Licence:
- CC Attribution (CC BY)
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