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CTNND2 is a genetic variant for high myopia
Author(s) -
SAW SM,
FAN Q,
YOSHIMURA N,
KHOR CC,
TAI ES,
GOH LK,
YOUNG T,
LI YL
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.2222.x
Subject(s) - meta analysis , replication (statistics) , single nucleotide polymorphism , genome wide association study , genetics , prospective cohort study , medicine , gene , bioinformatics , biology , oncology , genotype , virology
Purpose To determine novel genetic variants for high myopia in Singaporean Chinese. Methods A meta‐analysis of 2 genome‐wide association (GWA) datasets in Chinese and a follow‐up replication cohort in Japanese.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.Genomic DNA samples from SCORM and SP2 were genotyped using various Illumina Beadarray platforms (>HumanHap 500). High myopia, was defined by spherical equivalent (SE) ≤ ‐6.00 diopters (D) and controls defined by SE between ‐0.50 and +1.00 D.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. 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)). Conclusion 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.