title: A family-based association analysis and meta-analysis of the reading disabilities candidate gene DYX1C1.
abstract: Reading disabilities (RD) have a significant genetic basis and have shown linkage to multiple regions including chromosome 15q. Dyslexia susceptibility 1 candidate gene 1 (DYX1C1) on chromosome 15q21 was originally proposed as a candidate gene with two potentially functional polymorphisms at the -3G/A and 1249G/T positions showing association with RD. However, subsequent studies have yielded mixed results. We performed a literature review and meta-analysis of the -3G/A and 1249G/T polymorphisms, including new unpublished data from two family-based samples. Ten markers in DYX1C1 were genotyped in the two independently ascertained samples. Single marker and -3G/A:1249G/T haplotype analyses were performed for RD in both samples, and quantitative trait analyses using standardized reading-related measures was performed in one of the samples. For the meta-analysis, we used a random-effects model to summarize studies that tested for association between -3G/A or 1249G/T and RD. No significant association was found between the DYX1C1 SNPs and RD or any of the reading-related measures tested after correction for the number of tests performed. The previously reported risk haplotype (-3A:1249T) was not biased in transmission. A total of 9 and 10 study samples were included in the meta-analysis of the -3G/A and 1249G/T polymorphisms, respectively. Neither polymorphism reached statistical significance, but the heterogeneity for the 1249G/T polymorphism was high. The results of this study do not provide evidence for association between the putatively functional SNPs -3G/A and 1249G/T and RD.
authors: Genetics and Development Division, Toronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada.
authors: C
authors: C
authors: Tran
authors: F
authors: F
authors: Gagnon
authors: K G
authors: KG
authors: Wigg
authors: Y
authors: Y
authors: Feng
authors: L
authors: L
authors: Gomez
authors: T D
authors: TD
authors: Cate-Carter
authors: E N
authors: EN
authors: Kerr
authors: L L
authors: LL
authors: Field
authors: B J
authors: BJ
authors: Kaplan
authors: M W
authors: MW
authors: Lovett
authors: C L
authors: CL
authors: Barr
mesh_terms: D000293:Adolescent; D002170:Canada; D002648:Child; D003598:Cytoskeletal Proteins; D004410:Dyslexia / Q000235:genetics*; D005190:Family; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008957:Models, Genetic; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C478878:DNAAF4 protein, human; D005819:Genetic Markers; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins