Association study of developmental dyslexia candidate genes DCDC2 and KIAA0319 in Chinese population

Abstract

Developmental dyslexia (DD) is characterized by difficulties in reading and spelling independent of intelligence, educational backgrounds and neurological injuries. Increasing evidences supported DD as a complex genetic disorder and identified four DD candidate genes namely DYX1C1, DCDC2, KIAA0319 and ROBO1. As such, DCDC2 and KIAA0319 are located in DYX2, one of the most studied DD susceptibility loci. However, association of these two genes with DD was inconclusive across different populations. Given the linguistic and genetic differences between Chinese and other populations, it is worthwhile to investigate association of DCDC2 and KIAA0319 with Chinese dyslexic children. Here, we selected 60 tag SNPs covering DCDC2 and KIAA0319 followed by high density genotyping in a large unrelated Chinese cohort with 502 dyslexic cases and 522 healthy controls. Several SNPs (P min ¼ 0.0192) of DCDC2 and KIAA0319 as well as a four-maker haplotype (P adjusted ¼ 0.0289, Odds Ratio (OR) ¼ 1.3400) of KIAA0319 showed nominal association with DD. However, none of these results survived Bonferroni correction for multiple comparisons. Thus, the association of DCDC2 and KIAA0319 with DD in Chinese population should be further validated and their contribution to DD etiology and pathology should be interpreted with caution.

Neuroimaging genetics studies of specific reading disability and developmental language disorder: A review

“…Variation on DCDC2 has been associated with performance on several measures of reading and reading‐related skills including phonological skills, word/pseudoword reading, and spelling in samples with SRD (Chen, Zhao, Zhang, & Zuo, ; Ludwig, Roeske, et al, ; Marino et al, ; Matsson et al, ; Meng et al, ; Wilcke et al, ) and without SRD (Lind et al, ; Newbury et al, ; Powers et al, ; Scerri et al, ; Sun et al, ; Venkatesh, Siddaiah, Padakannaya, & Ramachandra, ; Zhang et al, ). Extant research suggests that variation in this gene is associated with subtle cortical malformations in brain areas important for reading (Meng et al, ).…”

KIAA0319 gene polymorphisms are associated with developmental dyslexia in Chinese Uyghur children

“…The SNP rs3756821 is located in the 5′ UTR of KIAA0319 and showed a nominal association with dyslexia in recent studies on the Chinese population but failed to show a significant association after Bonferroni correction in those studies. 15, 16 These results may imply that rs3756821 represents a risk-associated SNP for dyslexia in the Uyghur populations but not in the Chinese populations. This may be attributed to the genetic and linguistic differences among the Uyghur and Chinese populations, which could mean that genetic susceptibility to dyslexia occurs through different mechanisms.…”

“…1, 9, 10, 11, 12, 13, 14 The SNPs rs1091031, rs699463, rs3903801, rs12193738, rs2760157, rs807507, rs16889506, rs9366577, rs16889556, rs2038139 and rs3756821 were associated with dyslexia in the Chinese populations. 15, 16 …”

“…Its association with dyslexia was first proposed by Kaplan et al, 7 who found a microsatellite marker residing in KIAA0319 according to linkage studies. Since then, dyslexia– KIAA0319 association studies have been conducted in the US, 8 UK, 1, 9 German, 10 Canadian, 11, 12 Indian 13, 14 and Chinese 15, 16 populations, suggesting that several single-nucleotide polymorphisms (SNPs) are associated with the risk of reading disability, such as rs4504469, rs6935076 and rs2038137. However, the results have not always been consistent because of genetic and linguistic differences among ethnic groups.…”

The KIAA0319 Gene Polymorphisms are Associated with Developmental Dyslexia in Chinese Uyghur Children

“…(Kaplan et al 2002), who found a microsatellite marker residing in KIAA0319 according to linkage studies. Then, dyslexia-KIAA0319 association studies are conducted in US (Francks et al 2004), UK (Harold et al 2006;Cope et al 2005), German (Ludwig et al 2008), Canadian(Couto et al 2010;Elbert et al 2011), Indian (Venkatesh et al 2011;Venkatesh et al 2013) and Chinese (Lim et al 2014;Sun et al 2014) population, suggesting several risk SNPs are associated with reading disability, such as rs4504469, rs6935076 and rs2038137. However, the results are not 3 always consistent since the difference of genetic and linguistic between ethnic groups.…”