Opposite Associations between Individual KIAA0319 Polymorphisms and Developmental Dyslexia Risk across Populations: A Stratified Meta-Analysis by the Study Population.

Shanshan Shao,Yanfeng Niu,Jiajia Zhang,Jia Wang,Rui Kong,Ranran Song,Xiaohui Zhang,Xiu Luo,Lingfei Liu

doi:10.1038/srep30454

Abstract

KIAA0319 at the DYX2 locus is one of the most extensively studied candidate genes for developmental dyslexia (DD) owing to its important role in neuronal migration. Previous research on associations between KIAA0319 genetic variations and DD has yielded inconsistent results. It is important to establish a more precise estimate of the DD risk associated with these genetic variations. We carried out a meta-analysis of association studies involving KIAA0319 polymorphisms and DD risk. The results of pooled analysis indicated that none of the six investigated markers in or near the KIAA0319 gene are associated with DD. However, a stratified analysis by the study population revealed opposite associations involving KIAA0319 rs4504469 in European and Asian subgroups. The stratified analysis also showed that the KIAA0319 rs9461045 minor allele (T allele) has a protective effect in Asians. This meta-analysis has allowed us to establish the effects of specific KIAA0319 polymorphisms on DD risk with greater precision, as they vary across populations; analyzing one single nucleotide polymorphism at a time could not fully explain the genetic association for DD.

Highlights

6p22.2, a 77 kb region spanning the entire TTRAP and the first four exons of KIAA0319, which was found to be related to developmental dyslexia (DD) in two independent UK samples and one US sample; the authors suggested that a three-marker risk haplotype in this region was associated with DD16, thereby identifying KIAA0319 as a DD-associated gene
This power curve corresponds to the case with odds ratio 1/1.35 −1/1.15, which means odds ranges 0.74–0.87. It can detect the odds ratio smaller than or equal to 0.87 at power greater than 0.8. This meta-analysis of associations between six markers in or near the KIAA0319 gene and DD risk was based on seven case-control studies comprising a total of 2,711 cases and 2,991 controls and five TDT studies involving 943 families
A stratified analysis with the study population as the stratification factor revealed that KIAA0319 rs4504469 had opposite associations with DD risk in European and Asian subgroups

Summary

Introduction

6p22.2, a 77 kb region spanning the entire TTRAP and the first four exons of KIAA0319, which was found to be related to DD in two independent UK samples and one US sample; the authors suggested that a three-marker risk haplotype (rs4504469-rs2038137-rs2143340) in this region was associated with DD16, thereby identifying KIAA0319 as a DD-associated gene. We conducted a meta-analysis integrating the results from case-control and transmission/disequilibrium test (TDT) studies in order to derive a more precise estimate of the association between six markers in or near the KIAA0319 gene (Fig. 1) and DD risk.

Results

Conclusion