Study of Genetic Association With DCDC2 and Developmental Dyslexia in Hong Kong Chinese Children

Abstract

Background:Doublecortin domain-containing 2 (DCDC2) is a doublecortin domain-containing gene family member and the doublecortin domain has been demonstrated to bind to tubulin and enhance microtubule polymerization. It has been associated with developmental dyslexia and this protein family member is thought to function in neuronal migration where it may affect the signaling of primary cilia.Objectives:The objective of the study is to find out if there is any association of genetic variants of DCDC2 with developmental dyslexia in Chinese children from Hong Kong.Methods:The dyslexic children were diagnosed as developmental dyslexia (DD) using the Hong Kong Test of Specific Learning Difficulties in Reading and Writing (HKT-SpLD) by the Department of Health, Hong Kong. Saliva specimens were collected and their genotypes of DCDC2 were studied by DNA sequencing or TaqMan Real Time PCR Assays.Results:The most significant marker is rs6940827 which is associated with DD with nominal p-value (0.011). However, this marker did not remain significant after multiple testing corrections and the adjusted p-value from permutation test was 0.1329. Using sliding window haplotype analysis, several haplotypes were found to be nominally associated with DD. The smallest nominal p values was 0.0036 (rs2996452-rs1318700, C-A). However, none of the p values could withstand the multiple testing corrections.Conclusion:Despite early findings that DCDC2 is a strong candidate for developmental dyslexia and that some of the genetic variants have been linked to brain structure and functions, our findings showed that DCDC2 is not strongly associated with dyslexia.

Dyslexia-Related Loci Are Significantly Associated With Language And Literacy In Chinese-English Bilingual Hong Kong Chinese Twins

“…Genetic analysis on dyslexia or reading-related phenotypes was usually conducted in the European population, including the large cohort UK Avon Longitudinal Study of Parents and their Children(Luciano et al, 2013;Paracchini et al, 2008;Scerri et al, 2011), Australian Brisbane Adolescent Twin Study(Lind et al, 2010), and German population(Müller et al, 2016;Wilcke et al, 2009). There are three challenges to these kinds of studies:[1] Some of the signi cant associations cannot be replicated in other cohorts(Venkatesh et al, 2013) or survive after multiple testing correction(Waye et al, 2017). These inconsistent ndings call for more replication studies across different populations.…”