Dataset Information

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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Publications

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

Li Yi-Ju YJ Goh Liang L Khor Chiea-Chuen CC Fan Qiao Q Yu Miao M Han Siyu S Sim Xueling X Ong Rick Twee-Hee RT Wong Tien-Yin TY Vithana Eranga Nishanthie EN Yap Eric E Nakanishi Hideo H Matsuda Fumihiko F Ohno-Matsui Kyoko K Yoshimura Nagahisa N Seielstad Mark M Tai E-Shyong ES Young Terri L TL Saw Seang-Mei SM

Ophthalmology 20101120 2

<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]

PMID: 21095009

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Project description:BackgroundGenome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study.Methods2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r(2)>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ± 100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis.ResultsOf 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72 × 10(-14)). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs.ConclusionsWhile diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease.

Dataset Information

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

Objective

Design

Participants and controls

Methods

Main outcome measures

Results

Conclusions

Publications

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

Similar Datasets

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