Journal
OPHTHALMOLOGY
Volume 118, Issue 2, Pages 368-375Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ophtha.2010.06.016
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Funding
- Singapore BioMedical Research Council [06/1/21/19/466]
- US National Institutes of Health [1R21-EY-019086-01]
- BioMedical Research Council [03/1/27/18/216]
- Duke-NUS Graduate Medical School
- Research to Prevent Blindness, Inc.
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Objective: To determine susceptibility genes for high myopia in Singaporean Chinese. Design: A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese. Participants and Controls: Two independent datasets of Singaporean Chinese individuals aged 10 to 12 years (Singapore Cohort Study of the Risk factors for Myopia [SCORM]: cases = 65, controls = 238) and more than 21 years (Singapore Prospective Study Program [SP2]: cases = 222, controls = 435) for GWA studies, and a Japanese dataset aged more than 20 years (cases = 959, controls = 2128) for replication. Methods: Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina Beadarray platforms (>HumanHap 500). Single-locus association tests were conducted for each dataset with meta-analysis using pooled z-scores. The top-ranked genetic markers were examined for replication in the Japanese dataset. Fisher P was calculated for the combined analysis of all 3 cohorts. Main Outcome Measures: High myopia, defined by spherical equivalent (SE)<=-6.00 diopters (D); controls defined by SE between -0.50 and +1.00 D. Results: Two SNPs (rs12716080 and rs6885224) in the gene CTNND2 on chromosome 5p15 ranked top in the meta-analysis of our Chinese datasets (meta P = 1.14 x 10(-5) and meta P = 1.51 x 10(-5), respectively) with strong supporting evidence in each individual dataset analysis (max P = 1.85 x 10(-4) in SCORM: max P = 8.8 x 10(-3) in SP2). Evidence of replication was observed in the Japanese dataset for rs6885224 (P = 0.035, meta P of 3 datasets: 7.84 x 10(-6)). Conclusions: This study identified a strong association of CTNND2 for high myopia in Asian datasets. The CTNND2 gene maps to a known high myopia linkage region on chromosome 5p15.
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