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Genome-wide association studies reveal genetic variants in CTNND2 for high myopia in Singapore Chinese.


ABSTRACT:

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 × 10(-5) and meta P = 1.51 × 10(-5), respectively) with strong supporting evidence in each individual dataset analysis (max P = 1.85 × 10(-4) in SCORM: max P = 8.8 × 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 × 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.

SUBMITTER: Li YJ 

PROVIDER: S-EPMC3052933 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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<h4>Objective</h4>To determine susceptibility genes for high myopia in Singaporean Chinese.<h4>Design</h4>A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese.<h4>Participants and controls</h4>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]: cas  ...[more]

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