Original articleGenome-Wide Association Studies Reveal Genetic Variants in CTNND2 for High Myopia in Singapore Chinese
Section snippets
Study Populations
The SCORM and SP2 are the primary datasets in this study with genome-wide, high-density SNP data. The SCORM is one of the few cohorts with precise longitudinal ocular phenotypic data from predominantly Chinese Singaporean children.18 The SP2 is a population-based study of primarily Chinese adults aged 21 years or more with refractive error data.19, 20, 21, 22 Our study adhered to the Declaration of Helsinki. The SCORM was approved by the institutional review boards of the National University of
Genome-Wide Association Analysis Datasets
The basic demographic data for both SCORM and SP2 datasets are summarized in Table 1, and the description of SNPs selection process for meta-analysis of both cohorts is shown in Figure 1.
The post-QC SCORM GWA dataset comprised 929 subjects (481 male and 448 female) with refractive error data, of which 65 subjects have high myopia and 238 subjects are emmetropic controls. Because of 2 types of Illumina chips used in SCORM, only 541 849 autosomal SNPs were investigated. We excluded 69 801 markers
Discussion
This study used 2 GWA datasets of Singaporean Chinese with 287 high myopia cases and 693 controls of 2937 GWA samples, and a follow-up replication study in 3087 (959 high myopia cases and 2128 controls) Japanese. Because we combined refractive error data from children and adults, high myopia is likely the more robust phenotype, because children with high myopia are likely to remain highly myopic for life and phenotype reversal is rare.
We found significant association of the CTNND2 gene on
Acknowledgments
The authors thank the following Duke University affiliates: Carol Haynes, AB, for participation in the databasing of genotype data from the SCORM GWA study, Dr. Andrew Dellinger, PhD, for participation in providing initial assistance with the bioinformatics, and Dr. Dana Hornbeak, MD, for participation in generating the initial summary tables for the SCORM GWA study.
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Manuscript no. 2010-316.
Financial Disclosure(s): The authors have made the following disclosures: E-Shyong Tai: Consultant, Glaxo-Smith Kline; Consultant, Merck Sharp and Dohme (IA) Corp.
Funding: The SCORM GWA study is supported by the Singapore BioMedical Research Council, grant 06/1/21/19/466 to SSM and the US National Institutes of Health grant (1R21-EY-019086-01) to YJL. The SP2 GWA study is supported by BioMedical Research Council, grant 03/1/27/18/216 to EST. TLY is supported by research funding from the Duke-NUS Graduate Medical School, and Research to Prevent Blindness, Inc. Additional support was provided by the Singapore Tissue Network. The sponsor or funding organization had no role in the design or conduct of this research.
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These authors contributed equally to the manuscript.