title: 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.
  
  
  METHODS
  A meta-analysis of 2 genome-wide association (GWA) datasets in Chinese and a follow-up replication cohort in Japanese.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Goh
authors.forename: Chiea-Chuen
authors.initials: CC
authors.lastname: Khor
authors.forename: Qiao
authors.initials: Q
authors.lastname: Fan
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.forename: Siyu
authors.initials: S
authors.lastname: Han
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: Rick Twee-Hee
authors.initials: RT
authors.lastname: Ong
authors.forename: Tien-Yin
authors.initials: TY
authors.lastname: Wong
authors.forename: Eranga Nishanthie
authors.initials: EN
authors.lastname: Vithana
authors.forename: Eric
authors.initials: E
authors.lastname: Yap
authors.forename: Hideo
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ohno-Matsui
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Mark
authors.initials: M
authors.lastname: Seielstad
authors.forename: E-Shyong
authors.initials: ES
authors.lastname: Tai
authors.forename: Terri L
authors.initials: TL
authors.lastname: Young
authors.forename: Seang-Mei
authors.initials: SM
authors.lastname: Saw
mesh_terms: D044466:Asian People / Q000235:genetics*; D051177:Catenins / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D047728:Myopia, Degenerative / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011446:Prospective Studies; D012307:Risk Factors; D012846:Singapore / Q000453:epidemiology; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D000095002:Delta Catenin; C000722348:CTNND2 protein, human