Abstract
Dyslexia is a severe disorder in the acquisition of reading and writing. Several studies investigated the role of genetics for reading, writing and spelling ability in the general population. However, many of the identified SNPs were not analysed in case-control cohorts. Here, we investigated SNPs previously linked to reading or spelling ability in the general population in a German case-control cohort. Furthermore, we characterised these SNPs for functional relevance with in silico methods and meta-analysed them with previous studies. A total of 16 SNPs within five genes were included. The total number of risk alleles was higher in cases than in controls. Three SNPs were nominally associated with dyslexia: rs7765678 within DCDC2, and rs2038137 and rs6935076 within KIAA0319. The relevance of rs2038137 and rs6935076 was further supported by the meta-analysis. Functional profiling included analysis of tissue-specific expression, annotations for regulatory elements and effects on gene expression levels (eQTLs). Thereby, we found molecular mechanistical implications for 13 of all 16 included SNPs. SNPs associated in our cohort showed stronger gene-specific eQTL effects than non-associated SNPs. In summary, our results validate SNPs previously linked to reading and spelling in the general population in dyslexics and provide insights into their putative molecular pathomechanisms.
Highlights
Genes shown in Table 1) were not yet analysed in a dyslexia case-control setting, in these four genes only different single nucleotide polymorphisms (SNPs) were previously investigated (Supplemental Tables 1 and 2)
For all nominally associating SNPs, the observed risk alleles were in accordance to reported associations from the general population studies
Two of the three nominally associating SNPs were previously reported in case-control settings: For rs2038137-KIAA0319 the risk alleles were in accordance with the reported associations[19,20] and for rs6935076-KIAA0319 one study reported same allele[20] and one study reported the opposite allele as risk allele[21]
Summary
Genes shown in Table 1) were not yet analysed in a dyslexia case-control setting, in these four genes only different SNPs were previously investigated (Supplemental Tables 1 and 2). For the four of 16 SNPs case-control analyses already exist, information of additional association studies will provide valuable validation information helping to resolve partly contracting findings (Table 1). The primary aim of our study was to systematically investigate all these 16 SNPs in a German dyslexia case-control cohort. Other reported dyslexia candidate SNPs were analysed in this cohort (or subsets of this cohort). This information is valuable for an improved understanding of a potential pathomechanisms of an observed association It is important as additional evidence for the validity of an observed association.
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