Assessment for familial pattern and association of polymorphisms in KIAA0319 gene with specific reading disorder in children from North India visiting a tertiary care centre: A case–control study

Sharma, Pallavi; Sagar, Rajesh; Pattanayak, Raman Deep; Mehta, Manju; Subbiah, Vivekanandhan

doi:10.1002/dys.1642

Cited by 2 publications

(1 citation statement)

References 51 publications

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“…Support for involvement of these and other candidate risk genes has been reported from a variety of association and linkage studies in humans, and functional studies of brain development in rodents, but evidence is inconsistent [62][63][64][65][66][67][68]. There have been failures to detect linkage [69][70][71] or association [72][73][74][75][76][77][78], reports of association to opposite alleles [51,52,72], and demonstration of functional competence of the putative risk allele [79]. Meta-analyses have not resolved these conflicts [76,[80][81][82].…”

Section: Introductionmentioning

confidence: 99%

Targeted analysis of dyslexia-associated regions on chromosomes 6, 12 and 15 in large multigenerational cohorts

Raskind

Chapman

Navas

et al. 2023

Preprint

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Dyslexia is a common specific learning disability with a strong genetic basis that affects word reading and spelling. An increasing list of loci and genes have been implicated, but analyses to-date investigated only limited genomic variation within each locus with no confirmed pathogenic variants. In a collection of >2000 participants in families enrolled at three independent sites, we performed targeted capture and comprehensive sequencing of all exons and some regulatory elements of five candidate dyslexia risk genes (DNAAF4, CYP19A1, DCDC2, KIAA0319 and GRIN2B) for which prior evidence of association exists from more than one sample. For each of six dyslexia-related phenotypes we used both individual-single nucleotide polymorphism (SNP) and aggregate testing of multiple SNPs to evaluate evidence for association. We detected no promoter alterations and few potentially deleterious variants in the coding exons, none of which showed evidence of association with any phenotype. All genes except DNAAF4 provided evidence of association, corrected for the number of genes, for multiple non-coding variants with one or more phenotypes. Results for a variant in the downstream region of CYP19A1 and a haplotype in DCDC2 yielded particularly strong statistical significance for association. This haplotype and another in DCDC2 affected performance of real word reading in opposite directions. In KIAA0319, two missense variants annotated as tolerated/benign associated with poor performance on spelling. Ten non-coding SNPs likely affect transcription factor binding. Findings were similar regardless of whether phenotypes were adjusted for verbal IQ. Our findings from this large-scale sequencing study complement those from genome-wide association studies (GWAS), argue strongly against the causative involvement of large-effect coding variants in these five candidate genes, support an oligogenic etiology, and suggest a role of transcriptional regulation.

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